Pathologically confirmed metastatic or unresectable cholangiocarcinoma or gallbladder carcinoma (GBC), having received at least 1 prior line of systemic therapy, and received no more than 2 prior lines of therapy in the metastatic setting (disease recurrence < 6 months from the last dose of adjuvant therapy in resected patients will be considered the first line of therapy)\r\n* Includes intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), and gallbladder carcinoma (GBC), but not ampulla of vater cancers
Subjects may have had up to 8 cycles of standard first-line platinum-based chemotherapy for mUC (e.g., as per National Comprehensive Cancer Network [NCCN] guidelines); able to commence study treatment within 2 to 6 weeks of receiving last dose of first-line chemotherapy
Documented disease progression after at least 1 line of prior systemic therapy.
Patients must have progressed (in the opinion of the treating investigator) following the most recent line of therapy
Patients must have progressed radiographically following first line platinum-based chemotherapy, no additional lines of therapy are permitted\r\n* NOTE: Prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy\r\n* Exception for targeted therapy sub-study (Arm T): At least one line of prior chemotherapy or targeted therapy is required, but there is no limit on number of prior treatments
Patients must have either failed to achieve a complete remission, or must have relapsed within 2 years after completing first line bendamustine-containing chemoimmunotherapy (including an anti-CD20 monoclonal antibody), as measured from the last dose of bendamustine; relapsed patients must not have received any intervening chemotherapy; patients must have received at least 3 cycles of bendamustine as first line therapy; (note that no minimum dose of bendamustine is required); patients who additionally received any maintenance anti-CD-20 antibody based therapy or consolidative radioimmunotherapy within 2 years of the last dose of the bendamustine therapy are eligible; involved field or involved site radiation is not considered a line of therapy; patients who previously received anthracycline based therapy are excluded; examples of eligible 1st line treatment regimens (note this list is not all inclusive):\r\n* Bendamustine rituximab x 4 cycles\r\n* Bendamustine bortezomib rituximab x 6 cycles followed by rituximab maintenance\r\n* Bendamustine obinutuzumab x 3 cycles
1 prior line of systemic therapy for multiple myeloma, where a line of therapy for myeloma is defined as 1 or more planned cycles of single agent or combination therapy, as well as a planned series of treatment regimens administered in a sequential manner (e.g. lenalidomide, bortezomib and dexamethasone induction therapy for 4 cycles followed by autologous stem cell transplantation and then lenalidomide maintenance therapy would be considered 1 line of prior therapy); a new line of therapy begins when a planned therapy is modified to include other treatment agents (alone or in combination) as a result of disease progression, disease relapse or treatment-related toxicity (e.g. a patient is progressing in the face of lenalidomide maintenance therapy and has bortezomib and dexamethasone added into their regimen); a new line of therapy also begins when a planned treatment-free interval is interrupted by the need to start treatment due to disease relapse/progression (e.g. a patient with relapsed myeloma achieves a partial response after a planned 8 cycles of cyclophosphamide, bortezomib and dexamethasone, enjoys an 8-month period off therapy but then experiences disease progression requiring re-initiation of therapy)
Patients receiving targeted therapy (non-cytotoxic, non-immunotherapy based systemic therapy) for NSCLC in the first-line setting. Such designations would include but not be limited to treatments targeting EGFR mutant positive or ALK positive NSCLC in the first-line setting.
No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy)\r\n* Definition of one line of chemotherapy: One line of therapy can in some cases consist of 2 different cisplatin-based treatment combinations, provided there is no disease progression between these two regimens; for example, a patient could have received 2 cycles of bleomycin, etoposide, and cisplatin (BEP) followed by 2 cycles of cisplatin, ifosfamide, and etoposide (VIP) if the switch from BEP to VIP was made due to pulmonary toxicity rather than disease progression; this would be considered 1 line of prior therapy; in addition, if a patient received 4 cycles of BEP and then underwent post-chemotherapy resection of residual tumor with findings of residual viable non-teratomatous GCT, and subsequently received 2 additional cycles of adjuvant chemotherapy (etoposide, cisplatin [EP] or an alternate regimen such as VIP) in the absence of disease progression, this would also be considered 1 regimen; however, if any change in therapy is prompted by tumor progression including rising tumor markers, this is considered to represent 2 lines of prior treatment\r\n* Prior treatment with carboplatin as adjuvant therapy is allowed, provided patients meet other eligibility criteria (e.g., the patient has also received 3-4 cycles of cisplatin-based chemotherapy)\r\n* Prior treatment with 1-2 cycles of BEP or EP as adjuvant chemotherapy for early stage GCT is allowed, provided the patient also received 3-4 cycles of BEP or EP again at relapse; patients treated with 3-4 cycles of VIP at relapse following 1-2 cycles of BEP/EP are not eligible as this would be considered more than 1 line of prior therapy
SCLC, endometrial carcinoma: one prior chemotherapy-containing line.
For Phase 2 only, have had disease progression or be refractory or intolerant to 1 prior line of therapy (first line therapy) for recurrent or refractory for NSCLC or HCC and have refused currently approved second-line therapy. First line therapy is defined as therapy used to treat advanced disease. This may include multiple chemotherapeutic, targeted or immunotherapeutic agents with or without radiation therapy and/or surgery. Each subsequent line of therapy is preceded by disease progression. A switch of an agent within the same drug class (eg, cisplatinum to carboplatinum) within a regimen in order to manage toxicity does not define the start of a new line of therapy.
For Phase 2 only, more than 1 prior line of therapy for their tumor type.
At least 1 prior line of therapy
Expansion Phase: Initially, only immunotherapy naïve subjects who have progressed on first-line cytotoxic chemotherapy or who have declined first-line treatment with cytotoxic chemotherapy will be enrolled. Subjects with no prior systemic anti cancer therapy (i.e. first line therapy) may be enrolled in a second cohort if approved by the SMC. Subjects previously treated with systemic adjuvant therapy, other than immunotherapy for recurrent advanced NSCLC, are also eligible.
Previously treated with no more than one line of prior systemic therapy for stage IIIb or IV lung cancer\r\n* For patients who have previously treated one line of prior systemic therapy for stage IIIb or IV lung cancer, they must have exhibited evidence of disease progression clinically and/or radiographically on or after that treatment\r\n* Patients who previously received neoadjuvant, concurrent, or adjuvant chemotherapy for localized NSCLC and then recurred within 6 months of completing chemotherapy will be considered as having received one line of prior therapy; patients who relapse > 6 months after completing chemotherapy as part of neoadjuvant/concurrent/adjuvant therapy for localized disease, and thereafter receive additional one line of chemotherapy at the time of metastatic disease will be eligible\r\n* Maintenance therapy does not count as a separate line of therapy
Have progressed during or after completion of first line systemic chemo therapy\r\n* No limit to the number of prior chemotherapy regimens\r\n* Early progression on/after adjuvant chemotherapy counts as first-line therapy
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Actively on first line therapy for metastatic pancreatic cancer
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Patients may have had neo-adjuvant and/or chemotherapy that must have been completed > 3 months prior to starting first line therapy
INCLUSION CRITERIA FOR SECOND-LINE THERAPY: Patients may be actively on “maintenance” therapy, such as maintenance capecitabine up to starting first line therapy for metastatic disease
Patients must have received at least one prior line of targeted therapy
Received at least one prior line of therapy for incurable or metastatic NSCLC. Up to one prior line of checkpoint inhibitor therapy is permitted (must have received at least 6 months of treatment).
A line of therapy is defined as a course of therapy that is not interrupted by progressive disease; for example, induction therapy, autologous stem cell transplantation, and maintenance therapy without intervening progressive disease is one line of therapy
Must have relapsed or refractory disease after 2 or more prior lines of therapy; 1 line of therapy is allowed, if it included an autologous stem cell transplant and at least 12 weeks have elapsed from day 0; a line of therapy is defined as a course of therapy that is not interrupted by progressive disease
TREATMENT: Diagnosis of Hodgkin’s or non-Hodgkin’s lymphoma:\r\n* GROUP A: \r\n** With active disease \r\n*** In second or subsequent relapse\r\n*** In first relapse for indolent lymphoma after first line therapy for relapse\r\n*** Or first relapse if immunosuppressive chemotherapy contraindicated\r\n*** Primary refractory disease or if persistent disease after first line therapy of relapse\r\n** Or multiply relapsed patients in remission who are at a high risk of relapse or the lymphoma is a second malignancy e.g. a Richter's transformation of CLL after failing frontline therapy OR\r\n* GROUP B:\r\n** After autologous or syngeneic SCT (as adjuvant therapy)
Patients must have histologically documented metastatic solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after all Food and Drug Administration (FDA)-approved therapy; this trial will enroll a minimum of 5 lymphoma patients
Must not have received more than 4 lines of cytotoxic chemotherapy. A line of therapy is defined as being preceded by disease progression. Discontinuation of a regimen without progression (for example, due to toxicity) or a switch of an agent within the same drug class (for example from cisplatin to carboplatin) will not be considered a new line of therapy. Similarly, maintenance therapy (continuation maintenance or switch maintenance) will not be considered a new line of treatment.
If prior therapy consisted of palliative chemoradiation therapy, it will be considered one line of therapy.
Have received at least 1 prior line of therapy and meets at least one of the following criteria:
Experienced documented objective radiographic or clinical disease progression during first-line therapy or within 4 months after the last dose of first-line therapy with any platinum/fluoropyrimidine doublet with or without anthracycline (epirubicin or doxorubicin) or taxane (docetaxel) for unresectable or metastatic disease
Patients must have histologically documented metastatic solid tumors which have progressed after one line of therapy, or lymphoma which has progressed after all Food and Drug Administration (FDA)-approved therapy
Phase Ib: Subjects who progressed after first-line platinum-based chemotherapy and who are candidates for second-line therapy.
Prior treatment with one additional second line hormone therapy is permitted
More than one prior line of systemic therapy for advanced CRC
Patients must have histologically confirmed unresectable NSCLC for which nivolumab is clinically appropriate. Patients must have had one line of prior therapy and have progressed or have discontinued due to toxicity.
EXPANSION COHORT: Histologically or cytologically confirmed diagnosis of advanced pancreatic adenocarcinoma; \r\n* Maintenance group (n=10): Patients must be stable on front-line therapy (defined as at least 4 months stable disease on nab-paclitaxel + gemcitabine)\r\n* Second-line group (n=10): Patients must have failed or could not tolerate the front-line fluorouracil (5FU)-based therapy for advanced pancreatic cancer
Has received at most 1 line of prior non-gemcitabine chemotherapy for metastatic/unresectable disease\r\n* Prior adjuvant gemcitabine, if completed more than 12 months prior to enrollment is not considered as prior line of therapy\r\n* Radiosensitizing chemotherapy will not be considered a prior line of therapy
All patients must have had at least one appropriate first line systemic therapy and progressed
COHORT B, GROUP 5: MESOTHELIOMA: Patients must have failed a minimum of one previous line of systemic therapy for advanced disease
COHORT B, GROUP 7: GALLBLADDER CANCER OR CHOLANGIOCARCINOMA: Patients must have failed a minimum of one previous line of systemic therapy for advanced disease
All patients must be refractory to approved standard systemic therapy; specifically:\r\n* Metastatic colorectal patients must have received oxaliplatin or irinotecan\r\n* Hepatocellular carcinoma patients must have received sorafenib (Nexavar) since level 1 data support a survival benefit with this agent\r\n* Breast and ovarian cancer patients must be refractory to both first (1st) line and second (2nd) line treatments and must have received at least one second line chemotherapy regimen\r\n* Patients with recurrent glioblastoma that have received standard surgery, radiation therapy, and chemotherapy for their primary tumors and require resection of their tumors for palliative or other clinical indications; these patients will not undergo surgery solely for treatment on this protocol
Demonstrated disease progression during, or after discontinuation, of the most recent line of systemic therapy
Prior therapy with at least one first-line standard of care treatment or second-line treatment of proven effectiveness; patients must have progressive disease after prior treatment; prior first-line or second-line treatments would include the following:\r\n* Patients with metastatic melanoma: receipt of a checkpoint inhibitor as first-line therapy\r\n* Patients with metastatic melanoma with an activating mutation of KIT: receipt of imatinib\r\n* Patients with a BRAF V600 activating mutation: receipt of appropriate targeted therapy\r\n* Patients with metastatic gastrointestinal cancer: receipt of up to two forms of approved first- and/or second-line chemotherapy regimens\r\n* Patients with metastatic genitourinary cancers: receipt of a first- or second-line therapy appropriate for their histologic subtype
Previous first line treatment with at least radiotherapy.
Subjects must have progressed on or after standard first-line systemic chemotherapy
Refractory to approved standard systemic therapy; specifically\r\n* Patients with metastatic colorectal cancer must have received oxaliplatin or irinotecan\r\n* Patients with breast and ovarian cancer must be refractory to both 1st line and 2nd line treatments\r\n* Patients with lung cancer must have received at least one platinum-based chemotherapy regimen and at least one Food and Drug Administration (FDA) approved targeted treatment (when appropriate)\r\n* Patients with glioblastoma must have progression of disease after radiotherapy (including patients that undergo surgery for recurrent disease and are rendered no evidence of disease [NED]); this includes recurrent glioblastoma (GBM) after receiving all standard first-line treatment, including surgery (if feasible due to neurosurgical and neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy
Have a documented advanced (metastatic and/or unresectable) gastroesophageal adenocarcinoma that is incurable and for which prior first-line or later-line standard of care (SOC) treatments have failed. There is no limit to the number of prior treatment regimens. Prior neoadjuvant or adjuvant therapy included in initial treatment may not be considered first- or later-line SOC treatment unless such treatments were completed less than 12 months prior to the current tumor recurrence.
One prior line of chemotherapy and/or targeted agents for metastatic disease are permitted. This chemotherapy can include maintenance therapy, as long as it was given in the front line setting. In addition, prior antiangiogenic therapy (e.g. bevacizumab) is permitted if used as frontline treatment.
In the Phase 2 part, prior olaratumab/doxorubicin combination therapy in 1 prior treatment line is allowed.
Patients must have progressed on at least one prior line of chemotherapy, targeted therapy, palliative radiation and/or biological therapy regimen for their recurrent and/or metastatic HNSCC; however, if patients are likely to be intolerant to standard first-line systemic chemotherapy, the patients are eligible to enroll to this study as the first-line therapy
Patient may be enrolled at any time from last line of therapy
Patients with incurable, advanced or metastatic disease refractory to at least one previous line of therapy
Any line of prior therapy allowed.
At least one prior line of systemic treatment; if the only prior line of treatment was adjuvant or neoadjuvant, patient must have completed treatment within 12 months; there is no limit to number of prior therapies
Have had at least 1 prior line of standard therapy
Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or sandostatin treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy
Must have progressed on at least one line of prior therapy for metastatic disease, or be intolerant to that therapy if they have not progressed, and for HER2+ disease should have received prior trastuzumab
Patients must have progressed during or after first-line treatment for metastatic or unresectable disease with either a platinum-based regimen (e.g. carboplatin + etoposide, ifosfamide, and cisplatin [VP16], cisplatin + VP-16, leucovorin calcium, fluorouracil, and oxaliplatin [FOLFOX]) OR temozolomide-based regimen; patients must have failed at least one line of therapy but no maximum number of therapies is exclusionary (i.e. second-line therapy and beyond)
Patients should have received at least one line of approved chemotherapy and/or hormonal therapy
Must have had a relapse or progressive disease (PD) after having received 2 or more prior lines of systemic therapy. Note: A line of therapy is defined as 1 or more cycles of a planned treatment program; this may consist of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation (SCT), followed by maintenance is considered 1 line of therapy. Typically each line of therapy is separated by PD.
Prior allogenic bone marrow transplantation in any prior line of therapy or prior autologous SCT in the last prior line of therapy.
All patients must have progressed on at least one line of cytotoxic therapy for metastatic disease
Patients with DLBCL who have received chemotherapy or immunotherapy (except one week of steroids as described above) at any time point in the past for therapy of the DLBCL; patients with low grade B cell lymphomas who have received more than one prior line of chemotherapy or any anthracycline-containing therapy in the past for their low grade B cell lymphoma; localized radiation therapy does not count as a line of therapy
Pancreas patients must have progressed on at least 1 prior line of chemotherapy
Adequate vascular access for leukapheresis procedure (either peripheral line or surgically placed line)
One prior line of therapy is allowed.
Status post first-line therapy with definitive surgery (which provided tissue for pathologic diagnosis) and chemotherapy
Refractory disease is defined as no complete remission to first-line therapy; subjects who are intolerant to first-line therapy are excluded.
Stable disease (SD) as best response after at least 4 cycles of first-line therapy
Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven relapse ? 12 months of initiating first-line therapy
Subjects must have received adequate first-line therapy including at a minimum:
Prior therapy: eligible subjects must have had at least one line of platinum-based chemotherapy; this may be adjuvant therapy or first line of cytotoxic therapy for metastatic disease; prior hormonal therapy for metastatic/recurrent disease, prior targeted therapy, and prior radiotherapy are allowed; no maximum number of previous lines of chemotherapies; concomitant chemo-radiation is not considered as previous line of systemic chemotherapy
Pathologically confirmed PCNSL or PTL who failed or did not respond to at least 1 line of systemic therapy
Previous first line therapy with at least radiotherapy
Subject has received at least one line of prior therapy
Any line of prior therapy - patients may be chemo-naive or chemo-refractory (any line)
Primary refractory (at least 1 prior line of therapy)
Received more than 1 line of systemic treatment for advanced/metastatic CRC and/or a patient whose first line therapy did not contain oxaliplatin and bevacizumab
At least 1 prior line of chemoimmunotherapy if primary refractory or relapsed within one year; subjects who respond to initial therapy for greater than one year must have had at least 2 prior lines of therapy including one line with chemoimmunotherapy including an anti-CD20 monoclonal antibody
Progression during or after first line chemotherapy or chemoradiotherapy; prior maintenance therapy, targeted therapy, and immunotherapy are allowed; prior use of rovalpituzumab is allowed; immunotherapy or targeted therapy will not be considered as second line therapy
Patients must be appropriate candidates for letrozole therapy in any line of therapy or for fulvestrant for second line of therapy or beyond
Failed at least one line of chemotherapy; neoadjuvant and adjuvant chemotherapy count as a prior line of therapy
Received at least one prior line of therapy including immuno-chemotherapy.
Patients with unmutated (=< 2% homology with germ line) IGHV
Patients must have had front line therapy for their disease
Participants who received more than one line of previous therapy (including HD-ASCT), and have achieved a duration of response (CR or PR) of at least 8 weeks (from the last day of the last cycle) after their last line of therapy
Has primary refractory disease (this is, those whose tumors have progressed at the first restaging during first line therapy)
To be eligible for Cohort 6, patients must have failed one prior line of systemic therapy for advanced/metastatic disease
Phase 2: Subjects must not have received more than 1 prior line of therapy for locally advanced or metastatic NSCLC. First-line treatment must include an EGFR TKI, and subjects must have documented disease progression during or following treatment. Subjects with disease that progressed more than 6 months after completion of neoadjuvant/adjuvant chemotherapy or chemoradiation therapy are eligible if they received an EGFR TKI as first-line treatment for advanced NSCLC.
Refractory or relapsed myeloma, defined as one or more of the following: \r\n* Treated with first-line therapy including at least 2 cycles of lenalidomide, bortezomib or thalidomide, and one or more of the following: \r\n** Less than partial response (PR) to first-line therapy\r\n** Relapse after first (1st) line therapy\r\n* High-risk cytogenetics, defined by deletion (del)(13q) by conventional cytogenetics, or by del(17p), t(4;14), t(14;16), t(14;20) or 1q+ by fluorescence in situ hybridization (FISH)\r\n* Relapse after a prior autologous stem cell transplant (ASCT)\r\n* Plasma cell leukemia\r\n* Soft tissue plasmacytoma
ARM B COHORT 3: Patients must have failed one prior line of systemic therapy for the treatment of advanced non-small cell lung cancer; prior adjuvant therapy with subsequent recurrence within 6 months of completion of therapy will count as one prior line of systemic therapy and such patients will be eligible
ARM B COHORT 3: Patients must not have had more than one prior line of systemic therapy for advanced non-small cell lung cancer (including treatment with a targeted agent); prior adjuvant therapy completed more than 6 months prior to disease recurrence will not count as a prior line of systemic therapy for advanced disease
Patients must have documentation of a defined initial progression free interval (PFI 1) of greater than 6 months following front-line therapy
Patients must previously have received at least one prior line of therapy for their disease
At least 1 prior line of chemotherapy
Previously treated with no more than two lines of prior systemic therapy for advanced stage lung cancer\r\n* Patients who previously received neoadjuvant, concurrent, or adjuvant chemotherapy for localized NSCLC and then recurred within 6 months of completing chemotherapy may be considered as having received one line of prior therapy\r\n* Maintenance therapy does not count as a separate line of therapy
Participants must be within 6 months of initiating TKI treatment, which specifically targets the actionable mutation their tumor harbors (i.e., first-line TKI, or a next-line TKI that targets tumors with acquired resistance to first-line TKI)
Available Viralym-A T cell line.
Progressive disease or intolerable toxicities during or after treatment with first-line chemotherapy and have not received further second-line chemotherapy; patients treated with prior chemo-radiation to the primary pancreatic tumor, for which the chemotherapeutic agent was used as a radio-sensitizing agent, are eligible
Participants must have received at least one line of prior systemic chemotherapy and must have experienced documented radiographic progression or intolerance on this therapy
Follicular lymphoma, previously identified as CD19+\r\n* At least 2 prior chemotherapy or immunochemotherapy regimens (not including single agent monoclonal antibody therapy)\r\n* Patients who progress within 2 years after second or higher line of therapy will be eligible; for instance, patients who have progression of lymphoma < 2 years after second or greater line therapy, but who have responded to their most recent treatment (3rd line or higher) will be eligible; patients may have progression, stable disease or responding disease at the time of enrollment\r\n* Patients with a history of large cell transformation are eligible
Patients must have had, or refused first-line standard chemotherapy for their inoperable malignancies
documented progression on the most recent line of therapy
Patients whose tumors harbor an ALK rearrangement must have demonstrated progression on or intolerance to an FDA-approved first-line TKI; if the first-line TKI was crizotinib, then they also must have demonstrated progression on or intolerance to an FDA-approved second-line TKI; patients who received alectinib or ceritinib as first-line therapy and have demonstrated progression or intolerance will be eligible for this trial
Histologically documented advanced solid tumors that meet protocol-defined cohort specifications, have progressive disease at study entry, and have received at least one line of prior systemic therapy or for which no alternative therapy to prolong survival exists
Patients must have received one prior line of platinum-based systemic anticancer therapy for advanced or metastatic NSCLC. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued at the end of a treatment regimen.
Patients who never achieved at least minor response (MR) to at least one prior line of therapy
Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line)
Subjects with a central line-related mycobacterial infection; or
Have been previously treated with at least 1 prior line of MM therapy, and must have documented disease progression during or after their most recent therapy according to the IMWG criteria.
Recurrence or refractory to 1 line of systemic chemotherapy.
For Part 2, prior treatment with less than 2 prior line of chemotherapy
Stable on, or responding to 1st line therapy for metastatic disease \r\n* At least 8 and not more than 16 weeks after initiating 1st line therapy for metastatic disease\r\n* Tumor stability/response on 1st line therapy will be determined as per RECIST 1.1
Had at least one prior line of systemic chemotherapy for metastatic disease; adjuvant therapy would not count toward first-line therapy unless patient recurs less than 6 months after completion of that regimen
Patients must have prior chemotherapy for advanced CRC and have previously received both an oxaliplatin and an irinotecan based regimen; patients who are not appropriate for second line therapy because of their KRAS gene mutational status or because they cannot tolerate second line therapy, will be included even after only one prior therapy regimen
Patients must have had, or refused first-line standard chemotherapy for their inoperable malignancies
Failed first-line chemotherapy (including systemic and local-regional therapy)
Any line of treatment (first line versus beyond first line)
The dose of nilotinib for patients receiving the drug in the second line setting due to failure of a first line TKI is generally 400 mg PO BID; in addition, if a patient is unable to tolerate second line nilotinib at 400 mg PO BID their dose may be decreased to 300 mg PO BID; in both instances they will be eligible for phase I
The target population of this study are patients who have a suboptimal response to steroids as their first line of treatment for acute GVHD (ie steroid refractory); this protocol is designed to provide second line therapy, and is not for patients (pts) in whom additional, alternate immunosuppressive agents have already been added
First or second line chemotherapy treatment for metastatic disease
Patients must have received and completed first line therapy
Be receiving first-line therapy for metastatic disease
All patients must have also had a treatment-free interval without clinical evidence of progressive disease of at least 6 months from completion of front-line chemotherapy (both platinum and taxane); front-line therapy may have included a biologic agent (i.e. bevacizumab)
Previous first line therapy with at least radiotherapy and temozolomide.
For Parts 3 and 4, subjects must have progressed following at least 1 line of prior therapy, and the treatment with the select SOC agent is relevant for the specific disease cohort.
For participants who are ineligible for auto-SCT, has received at least ?2 lines of prior therapy and has failed to respond to or relapsed after their last line of treatment. For participants who received consolidative local radiotherapy after systemic therapy, local radiotherapy will not be considered as a separate line of treatment.
Must have failed last line of treatment (refractory to last line of treatment).
Must have undergone prior treatment with ?2 treatment lines of anti-myeloma therapy and must have failed last line of treatment (refractory to last line of treatment)
Hydroxyurea will not be considered a prior line of treatment.
Hydroxyurea will not be considered a prior line of treatment.
No more than one prior line of systemic treatment for glioblastoma. Concurrent and adjuvant TMZ-based chemotherapy, including the combination of TMZ with an investigational agent, is considered one line of therapy.
Have received a second line chemotherapy after progressing on or not tolerating treatment with FOLFIRINOX as a first line. Prior adjuvant/neoadjuvant gemcitabine or gemcitabine-based radiation will not be counted as first line therapy.
Must have failed last line of treatment (refractory to last line of treatment).
Occurrence or progression of BM while receiving first line therapy (either erlotinib, afatinib, or gefitinib) for at least 14 days. Patients may have received osimertinib (or other agents inhibiting the T790M EGFR mutation) as second line therapy. If BM progression occurs after osimertinib, patient will be eligible.
Subjects must have received at least 1 line of chemotherapy for metastatic MCC and must have progressed after the most recent line of chemotherapy
received at least one, but no more than three previous systemic regimens for the treatment of DLBCL and one therapy line must have included a CD20-targeted therapy
Patients must have progressed on or within 60 days after end of previous therapy before to study entry, i.e., refractory to the last line of treatment.
Has received a front line platinum-based regimen (administered via either intravenous or intraperitoneal route) per local standard of care or treatment guideline following the primary or interval debulking surgery with documented disease recurrence (note: Maintenance treatment following the front line treatment is permitted and counted together as part of the front line treatment)
Disease not amenable to standard treatment (nonresectable or disease present after one or more surgeries and/or sandostatin treatment) or subject has failed existing first line chemotherapy, biologic therapy, targeted agent therapy or radiation therapy
Achievement of SD or PR after a minimum of 12 weeks of pre-study first- or second-line standard chemotherapy
Up to 4 prior lines of systemic therapy (biologic or chemotherapy) are allowed; maintenance therapy after 4-6 cycles of front-line chemotherapy is still considered 1 line of therapy and is not considered 2 separate therapies
In Part A, prior treatment with at least one line of a single agent EGFR TKI and at least 1 line of chemotherapy.
Each subsequent line of therapy must be preceded by disease progression. A switch of an agent within a regimen in order to manage toxicity does not define the start of a new line of therapy
Prior treatment with nintedanib or any other prior line of therapy
For subjects who have discontinued anti-androgen therapy, PSA rise as defined above must be documented:\r\n* Within two weeks after discontinuation if used following surgical or medical castration (second line therapy)\r\n* After four weeks discontinuation if used as first line therapy
Prior anti-androgen therapy: first line of therapy (started simultaneously with LHRH) initiated at least eight weeks prior to screening; second line, anytime before start of study treatment
Any disease-directed radiotherapy (except prophylactic cranial irradiation or pre-planned radiotherapy for CNS metastases present prior to start of first-line therapy and non-progressing) after last dose of first-line chemotherapy.
The patient must have received no more than 1 prior line of therapy for extensive disease.
Progression after at least first-line systemic therapy for metastatic disease
Patients must have disease progressing after treatment with at least one line of therapy including mitotane and/or chemotherapy; Note: Patients who are deemed ineligible to receive first line treatment with mitotane and/or chemotherapy or who decline first line treatment may be eligible for this study after discussion with the principal investigator (PI)
Persistent, recurrent or progressive disease following at least one prior line of systemic therapy and there is no available therapy likely to improve survival
Patients must have failed at least one line of chemotherapy for metastatic disease.
Progression during or after prior first- or second-line chemotherapy and eligible to receive topotecan therapy
Failed first-line chemotherapy
Documented response of at least partial response (PR) to 1 line of prior therapy
ELIGIBILITY FOR TREATMENT ON ARM 1: Patients must have received at least one line of therapy for NSCLC or mesothelioma or previously documented to have declined therapy
Patients who have received second-line antihormonal therapy, including ketoconazole, aminoglutethimide, or high-dose estrogen within 30 days of study entry.
Previous first line therapy with at least radiotherapy and temozolomide
Disease status: all the patients need to have scan or biopsy proven active disease at the time of clinical trial\r\n* Multiple myeloma: patient must have failed at least one line of therapy\r\n* Chronic lymphocytic leukemia (CLL): status post (S/P) at least one line of therapy\r\n* Hodgkin’s lymphoma: S/P at least two lines of therapy\r\n* Follicular lymphoma: S/P at least one line of therapy\r\n* Mantle cell lymphoma: S/P at least one line of therapy\r\n* Diffuse large B cell lymphoma: S/P at least two lines of therapy
At least one prior line of platin-based chemotherapy (unless refused or not tolerated)
Patients must have had at least 2 prior line of therapy
Patient may be enrolled at any time from last line of therapy
Patients must have received first line chemotherapy, from 4-6 cycles, and achieved stable disease or a partial response
Multiple myeloma (MM) in first relapse or refractory to first line therapy; the previous line of therapy should include either an immunomodulatory agent or a proteasome inhibitor\r\n* Refractory disease is defined as =< 25% response or progression during therapy or within 60 days after completion\r\n* The number of prior lines of anti-myeloma therapy will be determined as follows:\r\n** Induction chemotherapy for peripheral-blood stem cell harvest followed by planned mobilization and subsequent high-dose chemotherapy with autologous stem cell transplant (ASCT) is considered one therapy regardless of the induction regimen\r\n** Planned maintenance therapy after stem cell transplantation or other induction therapy is not considered a separate line of therapy, as long as there is no evidence of progression in the time between the induction or transplantation and the initiation of maintenance therapy\r\n** Two ASCTs within 6 months of each other is considered as one line unless different agents were used in the high-dose therapy-conditioning regimens\r\n** If the same regimen is repeated after a 6-month interval, they are considered to be two separate therapeutic lines\r\n** If cyclophosphamide is used for reasons other than planned stem cell mobilization, its use is considered to be a separate line of therapy\r\n** Dose modification of steroid and altering choices of steroid (i.e. from dexamethasone to prednisone) due to side effects, is not considered a line of therapy, as long as there is no evidence of progression\r\n** If a regimen was stopped for more than 2 months, its re-initiation is counted as another line of therapy
At least one prior line of systemic therapy including platinum and pemetrexed
Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
Failed standard front-line therapy
Solid malignancy that is refractory to at least one prior line of treatment, or for which no standard therapy exists, is required; one prior line of treatment with irinotecan is allowed
For 1st Line expansion cohort ONLY, confirmation that the tumour is EGFRm+ve and have had no prior therapy for their advanced disease (for 1st line patients biopsy will be at time of diagnosis of advanced disease).
Failure of 1st line anti-cancer therapy due to radiological documentation of disease progression in advanced disease or subsequent relapse of disease following 1st line therapy
Received at least 1 prior line of therapy for MM (Phase 1)
Participants who relapsed from at least 1 previous treatment AND additionally were refractory to at least 1 previous treatment. For the purposes of this study, refractory disease was defined as disease progression on treatment or progression within 60 days after the last dose of a given therapy. A line of therapy was defined as 1 or more cycles of a planned treatment program. This may have consisted of 1 or more planned cycles of single-agent therapy or combination therapy, as well as a sequence of treatments administered in a planned manner. For example, a planned treatment approach of induction therapy followed by autologous stem cell transplantation, followed by maintenance was considered 1 line of therapy. Autologous and allogenic transplants were permitted.
High-risk disease as defined by one of the following: \r\n* First relapse after CR within 12 months of initiation of front-line therapy \r\n* Less than CR to front-line therapy \r\n* Second-line Age-Adjusted International Prognostic Index (sAAIPI) of 2 or higher at the time of relapse
Imaging studies documenting the response to first-line therapy must be available for evaluation by the investigator.
Have received more than 1 line of systemic treatment in Parts A, B and D
Documented progression from most recent line of therapy
* Primary tumor progression on first-line chemotherapy
Indication C - SS: Subjects previously treated with at least one prior line of approved therapy, including first-line anthracycline containing regimen.
Progression on or following, or intolerant of, at least one prior line of standard systemic therapy for advanced or metastatic gastric or pancreatic cancers.
Prior treatment\r\n* Currently receiving first-line treatment with pemetrexed + platinum; patients are to be registered to Cancer and Leukemia Group B (CALGB) 30901 no later than the last day of cycle 4 of first line therapy\r\n* Prior intracavitary cytotoxic or sclerosing therapy (including bleomycin) are acceptable; prior intrapleural cytotoxic chemotherapy will not be considered systemic chemotherapy\r\n* Prior surgical treatment is allowed\r\n* Prior radiation therapy is allowed
Subjects must have a pathologic diagnosis of advanced or recurrent endometrial adenocarcinoma and must have failed at least 1 prior line of standard chemotherapy
Any available standard line of therapy known to be life-prolonging or life-saving
Must have been treated with one of the following in first and/or second line:
Systemic treatment for B-cell CLL in the interval between completing the last cycle of second-line induction therapy and randomization.
Planned first-line chemotherapy contains a proteasome-inhibiting agent administered weekly
Received more than one line of chemotherapy
Must have received at least one (1) line of prior systemic therapy that may NOT have included VELCADE (bortezomib)
Patients whose tumors have progressed on first-line treatment
Participants who have received > 1 prior line of chemotherapy in the advanced or metastatic setting. (Immunotherapy will not be considered a line of chemotherapy.)
Participants who, after the front-line, platinum-based, non-docetaxel containing chemotherapy, have been treated with 1 line of nivolumab or other immune-checkpoint inhibitors but progressed on or after the therapy.
Must have received at least 3 cycles of first-line chemotherapy.
More than one prior line of chemotherapy (i.e., 2nd or 3rd line chemotherapy) for advanced and/or metastatic (stage III B or IV NSCLC) or recurrent disease.
Second-line or higher therapy for any patients with NSCLC with performance status (PS) 0-2
Participants may have received any number of prior lines of chemotherapy (other than erlotinib or other EGFR-targeted therapy) for incurable non-small cell lung cancer; (first line platinum-doublet based chemotherapy plus switch maintenance chemotherapy counts as one line of therapy; prior adjuvant chemotherapy for early stage disease does not count as one line of therapy if 12 months or greater elapsed between completion of adjuvant therapy and initiation of first-line systemic therapy; if less than 12 months elapsed, adjuvant chemotherapy counts as one line of therapy)\r\n* PARTICIPANTS WITH NO PRIOR THERAPY FOR INCURABLE LUNG CANCER: trial eligibility will be restricted to those participants whose tumors harbor known EGFR activating mutations\r\n* PARTICIPANTS WITH PRIOR LINES OF THERAPY: all other participants (those whose tumors harbor wild-type EGFR or unknown EGFR status, or those with EGFR mutations not previously treated with erlotinib/EGFR-targeted therapy)\r\n* At least 4 weeks must have elapsed since prior chemotherapy or biological therapy, 6 weeks if the regimen included carmustine (BCNU) or mitomycin C; prior radiation therapy to the thoracic cavity, abdomen, or pelvis must be completed at least 3 months prior to registration; radiotherapy to any other site (including bone or brain metastases) must be completed at least 28 days prior to registration
SCREENING: Patients must have received or refused first line standard systemic therapy for their metastases
Patient has received more than one line of chemotherapy for advanced disease.
Patients must have completed at least 1 prior line of systemic therapy; patients who have declined first line therapy or for whom first-line therapy would be clinically inappropriate, will be considered eligible for the trial
Patient has received any second line therapy to treat aGVHD prior to screening.
Must have received at least 1 prior line of AML therapy given at standard doses and must have progressed after their most recent therapy. Prior therapy must have included: a hypomethylating agent with at least 2 cycles.
Progressed following at least 1 line of prior therapy and there is no further approved therapy available that has been demonstrated to prolong survival (including subjects who are intolerant to the approved therapy)
second-line or greater salvage systemic therapy, or
Available Viralym-C T cell line
Patients must have already received or refused 1st-line treatment
More than one prior line of therapy for advanced gastric cancer
The cycles of chemotherapy must be consecutive (i.e. one followed by the other) but do not have to be the first and second cycle of a line of treatment.
Stable brain metastasis (defined as asymptomatic and off steroids ?3 months) are permitted in subjects entering LPT112515 on second-line treatment (completed 12-24 weeks of second-line treatment with trastuzumab plus chemotherapy)
Patients must have received one prior approved therapy for metastatic disease and have not curable options, with the exception of HER2+ breast or gastric patients for whom this can be the first line of treatment (no prior therapy)
Relapsed or refractory disease after at least one line of prior therapy. Subjects must have previously received appropriate line(s) of standard of care (SOC) treatment.
2nd line, 3rd line or greater
Patients with Hodgkin’s lymphoma with one or more of the following: \r\n* Less than complete response to first-line chemotherapy\r\n* Relapse within 12 months of completion of first-line chemotherapy\r\n* Relapse within a prior irradiation field\r\n* Less than complete metabolic response to second-line chemotherapy\r\n* Second relapse or beyond\r\n* Extranodal disease at the time of relapse\r\n* Presence of B symptoms at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease\r\n* Bulky disease (defined as any lesion greater than 5 cm) at the time of persistent disease upon completion of first-line chemotherapy, relapse or progressive disease
Patients must have failed one prior line of CT-based therapy for unresectable disease
No primary induction failure, defined as failure to achieve CR with first-line chemotherapy or chemoradiation, disease progression during first-line chemotherapy or chemoradiation, or progression or biopsy-proven disease persistence within 8 weeks of first-line therapy completion
Patients eligible for second-line therapy after failing first-line therapy with the regimen FOLFIRINOX.
Failure of rituximab for first-line treatment of PTLD. Note: Subjects with CD20 negative disease are eligible to enroll without prior anti-CD20 therapy after failure of first-line treatment (reduction of immunosuppression is not considered first-line therapy) and discussion with the sponsor's medical monitor.
Patients must have documented at least partial response (PR) to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment.
HCC patients only:\r\n* First line (i.e., no prior systemic therapy) or second-line (with prior first-line sorafenib therapy only) advanced HCC \r\n* Child Pugh class A or B7 liver disease \r\n* Prior chemoembolization, radioembolization, radiofrequency ablation (RFA), or other local ablative therapies are permissible if >= 6 weeks from procedure with evidence of progression or new metastatic disease, if applicable (Phase I)
Any progression during treatment if the len/dex combination was the subject's most recent line of therapy
Patients must have received at least one prior line of therapy and their disease has relapsed..
Must have had one prior line of systemic therapy for AL; Note: patients who do not achieve at least a PR to frontline therapy in 3 months may be eligible after discussion with study chair
Patients must have received first line standard systemic therapy for their metastases (if applicable)
First-line cytotoxic chemotherapy started within four-weeks of enrollment (patients can have reviewed prior = adjuvant therapy if completed >= 6 months prior to start of first line chemotherapy for metastatic disease)
Patients receiving 3rd-line palliative chemotherapy
Patients with cGvHD who have been exposed to one or more line of therapy, are eligible, providing they are refractory to, or dependent on, glucocorticoids (usually prednisone [PDN]); (in fact, it is anticipated that the majority of patients will be resistant to multiple lines of therapy); in the case in which the glucocorticoid dose-regimens cannot be confirmed accurately the use of one additional line of therapy will substitute
There must be no prior second-line or third line therapies for aGVHD (with exception of mycophenolate mofetil [MMF]) or second or third line therapies for cGVHD (other than extracorporeal photopheresis, rituximab or MMF); second and third line therapies for aGVHD and cGVHD are as defined by the British Committee on Standards in Hematology and reproduced in the GVHD Policy of the Blood and Marrow Transplant program (version 1-13); all prior therapies other than corticosteroids, tacrolimus, sirolimus or cyclosporine must be completed and discontinued; patients with breakpoint cluster region (bcr)-ABL proto-oncogene 1 (abl) associated malignancies may be on a tyrosine kinase inhibitor as malignant disease therapy or prophylaxis
Newly diagnoses or needing a new line of therapy and have not yet made a treatment decision
With income at or below 250% of the poverty line
Presence of an external central line
Have a central line in place prior to IV study therapy
Patients who are unable to have placement of intravenous line access
Well differentiated, low, intermediate, or high-grade, pancreatic NET with documented disease progression within 6 months prior to start of study treatment and evidence of radiographic disease progression based on scans performed not more than 15 months apart. Patients may have received 1 or more prior lines of anticancer therapy, such as somatostatin analogues, targeted agents, or liverdirected intra-arterial therapy, and up to 1 prior line of systemic cytotoxic chemotherapy, but are NOT eligible if they have received more than 1 prior line of systemic cytotoxic chemotherapy or if they have received prior peptide receptor radionuclide therapy (PRRT)
Patient is about to start a new line of ET for their metastatic disease
Subject must have metastatic or recurrent disease and have failed first-line systemic treatment, and if indicated, failed approved second-line therapy, and for whom no standard therapy options are anticipated to result in a durable remission
Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to sub-study registration; patients must have recovered (=< grade 1) from any side effects of prior therapy; patients must not have received any radiation therapy within 14 days prior to sub-study registration
>= 1 prior systemic therapy for sarcoma, including adjuvant systemic therapy
Patients must have had no prior systemic therapy
GCTs: no limit of prior therapy
The last dose of prior systemic therapy (e.g. chemotherapy, targeted therapy etc) or radiation therapy (with the exception of palliative radiotherapy) was received less than 14 days prior to the first day of treatment
Have progressed on prior systemic therapy
Phase 1b only: Advanced solid malignancy with an emphasis on colorectal, head and neck, breast, pancreatic and ovarian cancers who have been treated with at least one regimen of prior systemic therapy, or who refuse systemic therapy, and for which there is no curative therapy available.
Relapsed or are refractory to at least 1 prior systemic cytotoxic therapy. -Subjects must have received conventional therapy as a prior therapy.
Prior systemic therapy for incurable disease
Prior systemic therapy:\r\n* Participants must have discontinued systemic therapy at least 14 days prior to initiating protocol therapy.\r\n* There is no limit to the number of prior lines of systemic therapy. Participants who have not received any systemic therapy for metastatic disease are also eligible.\r\n* Participants may initiate or continue bisphosphonate therapy on study
Patients must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their sarcoma if standard treatment is appropriate. Treatment naive patients may be enrolled if they have refused standard systemic treatment. Prior adjuvant therapy will not count provided it was completed more than 6 months previously.
A) Patients enrolled into the dedifferentiated liposarcoma cohort do not require prior systemic therapy (may be naive to systemic therapy); B) leiomyosarcoma patients must have had at least 1 prior systemic therapy (does not include adjuvant/neoadjuvant therapy in a curative setting). There are no limits on prior number of therapies for either cohort
Patients must have been treated with at least one prior systemic regimen for sarcoma; adjuvant systemic therapy qualifies as prior therapy for the purposes of this study; there is no upper limit on previous lines of therapy received; a prior line of systemic therapy may include prior investigational agents received as part of other clinical studies
Must have received at least one prior systemic therapy
Prior therapy with any systemic therapy (chemotherapy or biologic therapy) within twenty-eight days prior to study entry
Prior systemic chemotherapy or therapy with one of the investigational agents within 1 month prior to enrollment
Prior systemic therapy
Prior malignancies requiring systemic therapy within the last 3 years (as prior therapy can increase toxicity of current chemo regimen, those patients should be excluded).
Patients may have received prior systemic and/or radiation therapy. All adverse events associated with prior systemic therapy or radiation therapy must have resolved to =< grade 1 prior to start of study
No prior systemic therapy for lymphoma
Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their sarcoma; an exception to this criterion will be made for patients with sarcoma histological subtypes for which there is no known standard systemic therapy (e.g., chondrosarcoma); any patient that refuses standard chemotherapy for the treatment of their disease is also considered eligible; prior adjuvant therapy will not count provided it was completed more than 6 months previously
No prior therapy for this disease
Have received any number of prior systemic therapies for metastatic disease; prior radiation therapy (any number) and interferon use (any formulation and/or duration) in the adjuvant or metastatic disease settings is permitted; vaccine therapy will be counted as systemic therapy
Systemic therapy is allowed but SBRT cannot begin until >= 7 days after the last cycle of systemic therapy, and systemic therapy cannot be initiated or re-initiated until >= 7 days after SBRT; there will be no limit on prior lines of systemic therapy
Prior systemic chemotherapy, immunotherapy, or biological therapy, radiation therapy and/or surgery are allowed; prior use of systemic methotrexate > 1 month prior to study entry is allowed. Intrathecal methotrexate is allowed prior to and during treatment per investigator discretion.
Prior systemic therapy or radiation therapy for treatment of the current lung cancer
Must have received at least one prior systemic therapy, and must have relapsed or progressed after, or failed to respond to any/all available effective therapy or therapies.
Subjects must have at least one prior line of systemic therapy (e.g. chemotherapy, immunotherapy, targeted or biological therapy) for their sarcoma; an exception to this criterion will be made for patients with sarcoma histological subtypes for which there is no known standard systemic therapy (e.g., chondrosarcoma); prior adjuvant therapy will not count provided it was completed more than 6 months previously
At least 14 days must have elapsed since any prior systemic therapy prior to apheresis and prior to the initiation of chemotherapy (including systemic corticosteroids at any dose); systemic anti-malignancy therapy including systemic corticosteroid therapy of any dose is not allowed within 14 days prior to the required leukapheresis\r\n* NOTE: 30 days must elapse from the time of administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the principal investigator (PI) can stimulate immune activity and infusion of CAR T cells
At least one prior systemic treatment (including neoadjuvant therapy) for their tumor of the small intestine, with intolerance to prior therapy, failure of the most recent therapy (of any line) or recurrent disease
Metastatic renal cell cancer patients (any histologic subtype) with measurable and/or evaluable disease who have completed at least one line of prior systemic therapy are potentially eligible for this trial; any number of prior systemic therapies are allowed, including prior nivolumab
No prior systemic chemotherapy for transitional cell carcinoma of the bladder (prior intravesical therapy is allowed); any other prior chemotherapy must have been completed > 5 years prior to initiation of therapy
Patients may have received prior systemic and/or radiation therapy; all adverse events associated with prior systemic therapy or radiation therapy must have resolved to =< grade 1 prior to start of study
At least 14 days must have elapsed since any prior systemic therapy prior to apheresis and prior to the initiation of chemotherapy (including systemic corticosteroids at any dose); systemic anti-malignancy therapy including systemic corticosteroid therapy of any dose are not allowed within 14 days prior to the required leukapheresis; NOTE: 60 days must elapse from the time of administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the principal investigator (PI) can stimulate immune activity and infusion of CAR T cells
May have received at least 1 prior therapy for recurrent or metastatic disease, up to 2 prior systemic therapies.
Completion of prior systemic therapy at least 14 days prior to enrollment
No more than 3 prior progressions
Prior therapy
Planned systemic therapy after orbital radiation therapy is permitted however the timing of systemic therapy will be recorded and patients will be stratified according to receipt of adjuvant systemic therapy
Prior systemic therapy
Prior therapy for melanoma that may include surgery, radiation therapy, immunotherapy including interleukins and interferon, and/or ?2 different regiments of systemic chemotherapy, targeted therapy, or other experimental systemic therapies. Prior treatment with immune checkpoint inhibitors is not allowed.
Systemic immunoglobulin therapy within the last 30 days
Candidate for further therapy and able to wait 7 days prior to start of next systemic therapy
Patients must be refractory or intolerant to at least 1 prior standard systemic therapy, if a candidate for systemic therapy
Patients who have received topical therapy, systemic chemotherapy, or biological therapy within 4 weeks prior to registration are NOT eligible for participation
Patients may not have received prior systemic chemotherapy for metastatic/advanced urothelial carcinoma; note: prior neoadjuvant/adjuvant therapy is permitted if completed >= 12 months prior to registration for protocol therapy; prior intravesical therapy is permitted
Prior AQ4N therapy.
Failed at least 1 prior systemic therapy
History of prior treatment with at least one line of systemic anticancer therapy, when an approved systemic therapy is available, and no curative option is available for continued treatment
Prior systemic treatment
Patients must have never received any prior systemic therapy for their disease.
Patients who have had systemic therapy or radiotherapy within 3 weeks prior to the first dose of study therapy
Patients must have received at least one prior systemic therapy for lymphoma; a washout period of at least 3 weeks is required from the most recent prior therapy
Has had prior systemic therapy (exception: GnRH agonist or antagonist) or radiation therapy for prostate cancer within 2 weeks prior to study day 1; there must be at least a 2 week washout period from last dose of any prior systemic or radiation therapy for prostate cancer prior to day 1 of study treatment (including nonsteroidal antiandrogens); screening may commence during this washout window
Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to Step 2 re-registration; patients must have recovered (=< grade 1) from any side effects of prior therapy
Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to re-registration; patients must have recovered (=< grade 1) from any side effects of prior therapy
Patients must not have received any prior systemic therapy (systemic chemotherapy, immunotherapy or investigational drug) within 21 days prior to step 2 re-registration; patients must have recovered (< grade 1) from any side effects of prior therapy
Patients must not have received any prior systemic therapy (chemotherapy or other biologic therapy) for their unresectable malignant pleural mesothelioma; prior systemic chemotherapy or biologic therapy is allowed as neoadjuvant or adjuvant treatment, disease has now recurred, and all systemic treatment was completed > 6 months prior registration; prior therapy must not have included cediranib
Prior resection permitted, no prior systemic, ablative or infusion therapy permitted
Patient has not received prior anti-angiogenic therapy, systemic targeted agents or systemic chemotherapy\r\n* Prior surgical resection, chemoembolization or other local therapy prior to transplant is permitted
Prior Therapy Criteria:
Prior systemic therapy requirements.
Prior systemic chemotherapy (prior intravesical therapy is allowed)
Patients must not have received any prior systemic therapy (chemotherapy or other biologic therapy) for lung cancer
Subject has received no prior systemic therapy
Must not have received any prior systemic therapy for their mRCC.
Prior systemic therapy or radiation therapy for treatment of the current lung cancer
Prior malignancy requiring systemic therapy or radiation therapy within 1 year of randomization
Prior treatment with any type of systemic therapy for advanced disease.
Prior systemic therapy within 14 days of study enrollment; patients must be adequately recovered from prior systemic therapy side effects as deemed by the treating investigator
Prior systemic chemotherapy (prior intravesical therapy is allowed)
Relapsed or are refractory following at least 2 prior systemic therapeutic attempts (1 prior systemic attempt for PTCL). For CTCL, extracorporal photochemotherapy (ECP) will be considered a systemic therapy. Local radiation and topical agents are not systemic therapies.
NSCLC that has progressed during or following 1 - 5 prior systemic therapies for unresectable locally advanced or metastatic disease (at least one docetaxel, gemcitabine, or platinum analogue based therapy), or are intolerant of or refused standard cancer therapy. For squamous cell carcinoma, or adenocarcinoma without known activating mutation: the prior systemic therapy is at least one platinum analogue. For adenocarcinoma with known activating driver mutation: the prior systemic therapy is at least TKI directed
No systemic therapy for RRP for four weeks prior to treatment
Prior systemic therapy for WM
No prior systemic therapy administered in the recurrent or metastatic setting (with the exception of systemic therapy completed > 6 months prior if given as part of multimodal treatment for locally advanced disease)
Prior RRx-001 therapy
No more than 2 prior courses of systemic therapy for metastatic melanoma
Prior treatment with sunitinib or any other systemic therapy in the metastatic setting (prior neo/adjuvant therapy will be allowed if completed > 6 months prior to registration and therapy not discontinued for toxicity)
Disease Status and Prior Therapy:
Prior Therapy
Patients may have received prior systemic therapy (chemotherapy, immunotherapy, biologic therapy, or combination regimens); all adverse events associated with prior treatment must have resolved to =< grade 1 prior to registration
Subjects who have failed at least one prior course of systemic therapy. Psoralen plus ultraviolet light therapy (PUVA) is not considered to be a systemic therapy
Prior systemic chemotherapy (prior intravesical therapy is allowed)
Participants with pcALCL who have received prior radiation therapy or at least 1 prior systemic therapy; participants with MF who have received at least 1 prior systemic therapy
Patients may have received prior systemic chemotherapy; such therapy must have been completed at least 5 years prior to study entry and the patient has no evidence of disease subsequent to such therapy
Prior systemic therapy within 28 days of study enrollment
No prior systemic therapy for lymphoma including chemotherapy or immunotherapy. Patients may have received involved-field radiation therapy which has been discontinued at least 4 weeks prior to treatment in this study.
No prior systemic therapy; prior adjuvant therapy with interferon does not count
Received at least one regimen of prior systemic therapy and then experienced documented radiographic progression or was not able to tolerate prior systemic therapy.
Patients who have received no prior systemic therapy as well as those who have received prior systemic therapy for PRCC. Patients who have received prior therapy must have had disease progression within 6 months of the last dose of previous systemic therapy
Has received prior systemic therapy for the treatment of SCLC
Prior therapy
Previous use of systemic therapy for bone metastasis is allowable as long as the systemic therapy use fits within the treatment plan as described in Proposed Treatment/Study Plan; (if the patient received less than 3 - 9 months of systemic therapy previously, the use of additional systemic therapy may be necessary to fit within the treatment plan)
Patients with immanent risk of fracture(s) may receive local therapy prior to systemic therapy; otherwise systemic therapy should be given first
Prior therapies:\r\n* Patients may have received one line of non-gemcitabine containing chemotherapy regimen\r\n* Patients may have received prior adjuvant chemotherapy and/or radiation therapy greater than 6 months prior to the time of study enrollment\r\n* Patients may have received “maintenance” therapy, e.g. lower dose capecitabine after completion of adjuvant therapy; this will not be considered as therapy for metastatic disease AND will patients may have been on maintenance therapy within the 6 months prior to initiating gemcitabine plus nab-paclitaxel, i.e. right up until the initiation of first-line therapy for metastatic disease\r\n* Timing of prior therapies:\r\n** At least 14 days must have passed since all prior anti-cancer therapy, including chemotherapy, biological therapy, or radiation therapy, and any prior investigational agent\r\n** However, at least 21 days must have passed since any prior antibody-based therapies (such as, but not limited to cetuximab or bevacizumab)\r\n** All patients must have completely recovered from all transient side effects related to prior therapies\r\n*** However, any side effects that are expected to be more durable or even permanent (e.g., neurotoxicity or ototoxicity) must have resolved to at least grade 1
Prior Therapy
Prior therapy:
For Phase II: Any prior systemic therapy for locally advanced or metastatic melanoma; prior local therapy such as radiation or intratumoral injection is allowed; previous systemic treatment for any stage III disease that was subsequently rendered NED (no evidence of disease) by surgery is allowed
Prior systemic chemotherapy (prior intravesical therapy is allowed)
Prior therapy with an hypoxic cytotoxin
Treatment naïve or has received only one systemic therapy apart from adjuvant therapy.
Prior therapy defined as 1 prior systemic therapy for advanced disease
History of prior treatment with at least one line of systemic anticancer therapy, when an approved systemic therapy is available, and no curative option is available for continued treatment.
For participants with recurrent SCCHN, prior systemic therapy is allowed if it was given as part of induction or definitive therapy. If participants have received prior combined chemo-radiation therapy, they must be off therapy for at least 3 months
Failure of at least one prior therapy
At least one prior therapy;
Part D - Diagnosed with cholangiocarcinoma and have not received more than 1 prior systemic therapy
Prior therapy for this cancer
Prior treatment with Scrambler therapy
Hepatic locoregional therapy following prior systemic therapy or within 28 days prior to randomization.
Any prior systemic therapy is permitted (except cisplatin or carboplatin)
Patients with small cell carcinoma must have progressed after at least one prior systemic therapy; patients with squamous cell carcinoma or adenocarcinoma may be previously untreated or have progressed after prior systemic therapy; chemotherapy administered in conjunction with primary radiation as a radio-sensitizer WILL be counted as a systemic chemotherapy regimen; NOTE: There is no maximum number of prior treatments allowed
Prior therapy is allowed
Patients with metastatic disease may have received prior nephrectomy and/or prior systemic therapy (no limit on number); their baseline pMRI would be performed prior to starting a new treatment
Prior systemic cancer therapy
No prior therapy for IDC or ILC
No prior therapy for disease under study
CRITERIA FOR SYSTEMIC THERAPY WITH ERLOTINIB
Patients with refractory or relapsed JMML must have had at least one cycle of intensive frontline therapy or at least 2 cycles of a deoxyribonucleic acid (DNA) demethylating agent with persistence of disease, defined by clinical symptoms or the presence of a clonal abnormality; frontline therapy is defined as one cycle of intravenous chemotherapy that includes of any of the following agents: fludarabine, cytarabine, or any anthracycline but specifically excludes oral 6-mercaptopurine; frontline therapy will also include any conditioning regimen as part of a stem cell transplant; patients who transform to acute myeloid leukemia (AML) with more than 20% blasts at relapse are not eligible for this trial
Have at least one evaluable and measurable lesion as defined by RECIST v1.1. Subjects who have received prior local therapy (including but not limited to embolization, chemoembolization, radiofrequency ablation, or radiation therapy) are eligible provided measurable disease falls outside of the treatment field or within the field and has shown ?20% growth in size since post-treatment assessment.
Underwent hepatic radiation, chemoembolization, and radiofrequency ablation <4 weeks prior to Day 1.
Radiopharmaceutical therapy (e.g., radiolabeled antibody, 131 iodine metaiodobenzylguanidine [131I-MIBG]): >= 42 days after systemically administered radiopharmaceutical therapy
Hormone replacement therapy of any type, megestrol acetate, or raloxifene within one week prior to registration
Patients with tumors with the following molecular alterations must submit testing results via Medidata Rave to determine eligibility to Arm T; the study chair, co-chair, biology co-chair, or a delegate must review the molecular testing and agree that the testing meets eligibility outlined below:\r\n* ROS1 gene rearrangement by fluorescence in situ hybridization (FISH) or deoxyribonucleic acid (DNA) analysis (may have progressed on prior crizotinib therapy)\r\n* MET exon 14 splice mutations on DNA analysis (may have progressed on prior crizotinib therapy)\r\n* MET high amplification by FISH or DNA analysis or other MET mutations predicted to be sensitive to MET inhibitor (no prior targeted therapy allowed)\r\n* RET gene rearrangement by FISH or DNA analysis (no prior targeted therapy allowed)\r\n** Institutions will be notified of the patient’s eligibility status for Arm T within two (2) business days of submission of the molecular testing reports\r\n** If patients do not have tumors with the above molecular alterations noted proceed directly to step 1
Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound [HIFU]) for prostate cancer is allowed; prior focal HIFU or treatment for benign prostatic hypertrophy is allowed
No waiting period for patients who relapse while receiving standard maintenance therapy
With the exception of intrathecal chemotherapy (methotrexate strongly preferred; cytarabine is permissible) administered at the time of the required diagnostic lumbar puncture to establish baseline CNS status, patient has not received prior relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of first relapse)
Treatment with hydroxyurea, corticosteroids (any route) and intrathecal cytarabine prior to beginning protocol directed therapy is allowed; however, it should be noted that lumbar puncture and intrathecal therapy at initial diagnosis of APL is not recommended
With the exception of steroid pretreatment or the administration of intrathecal methotrexate or intrathecal cytarabine, receipt of any other prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL15P1
Prior therapy\r\n* Patients =< 30 days from the last dose of cytarabine used for treatment of TMD
Prior whole gland ablative therapy (i.e. cryoablation or high intensity focused ultrasound [HIFU]) for prostate cancer is not allowed
No prior therapy for ALL except for limited treatment (=< 7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine; however, patients who are being treated with chronic steroids for other reasons (for example, to treat asthma, autoimmune disorders, lupus, etc.) are eligible
No prior therapy for acute leukemia except emergency therapy (corticosteroids or hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange transfusion is recommended to reduce the WBC
Single-dose intrathecal cytarabine is allowed prior to registration or prior to initiation of systematic therapy for patient convenience; systemic chemotherapy must begin within 72 hours of this intrathecal therapy
Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen therapy is allowable).
Prior chemotherapy or tumor directed therapy (i.e. radiation therapy, biologic agents, local therapy (embolization, radiofrequency ablation, and laser); therefore, patients with a pre-disposition syndrome who have a prior malignancy are not eligible
Part B: More than 6 cycles of prior therapy with carboplatin
Parts B1, B3, and C: During prior platinum therapy, requirement for dose reduction or discontinuation of carboplatin or cisplatin for toxicity or lack of tolerability
No prior chemotherapy, radiation therapy, or surgery for this malignancy will be allowed; prior endoscopic procedures for superficial disease (endoscopic mucosal resection, cryotherapy, photodynamic therapy, etc.) will not exclude a patient; prior dilatation is also allowed
Corticosteroid therapy and endocrine replacement therapy (L-thyroxine, testosterone, estrogen, desmopressin acetate [DDAVP]) are permissible; any patient already receiving human growth replacement therapy should discontinue this prior to commencing chemotherapy, and should not restart until 3 years from diagnosis
Prior therapy with a toll-like receptor (TLR) agonist, excluding topical agents.
Prior CAR T-cell or other genetically-modified T-cell therapy
Disease Characteristics and allowable prior therapy:
Prior medical therapy is allowed but not required
Refractory/relapsed disease following DNMTi failure; refractory disease defined as either 1) failure to achieve an objective response after at least 4 cycles of DNMTi therapy, or 2) failure to achieve an objective response with clear progressive disease on bone marrow biopsy after at least 2 cycles of DNMTi therapy; relapsed disease is defined as having progressive disease after achieving an objective response after at least 2 cycles of DNMTi therapy; previous DNMTi therapy may include 5’azacitidine, decitabine, or DNMTi therapy currently in clinical trials (e.g. SGI-110 [guadecitabine], ASTX727 or CC-486); to be considered DNMTi treatment failure, during each prior treatment cycle, patients must have received minimum dosing of:\r\n* Decitabine 15 mg/m^2 daily x 5 days, or\r\n* 5’azacitidine 50 mg/m^2 IV/SC daily x 5 days,\r\n* SGI-110 (guadecitabine) 60 mg/m^2 SC daily x 5 days, or\r\n* Oral DNMTi therapy with ASTX727 20/100 mg daily x 5 days, or\r\n* Oral DNMTi therapy with CC-486 200 mg daily x 14 days
For prior cytotoxic therapy, treatment for 1 full cycle or less will not be considered as prior therapy unless the patient experienced progression of disease while on that therapy.
Received other recent antitumor therapy including any standard chemotherapy or radiation within 14 days (or have not yet recovered from any actual toxicities of the most recent therapy) prior to the first scheduled dose of MM-310
All hematologic, gastrointestinal, and genitourinary chemotherapy toxicities must be less than Grade 2 at the time study therapy is to begin. (Note: Transfusions may be used to correct hemoglobin for patients experiencing anemia from therapy who otherwise would be eligible for the study.
Cutaneous, subcutaneous soft tissue, or superficial lymphatic metastasis that is amenable to injection and irradiation and > 10 mm in longest dimension\r\n* Cutaneous metastasis in a region of previous radiation therapy is amenable to radiation therapy as part of this protocol if at least 6 months has elapsed since prior radiotherapy and the dose of radiotherapy previously administered did not exceed an equivalent dose of 60 Gy in 2 Gy equivalent fractions at the skin surface (using linear-quadratic modeling with alpha/beta = 11.5)
Prior cytoreductive therapy.
Patients who progressed after initial therapy\r\n* Subjects whose therapy changed due to suboptimal response, intolerance, etc., remain eligible, provided they do not meet criteria for progression\r\n* No more than two regimens will be allowed excluding dexamethasone alone
Prior therapy with abemaciclib
Prior radioisotope therapy
Patients must not have received prior systemic therapy for PTCL (except for corticosteroids for 10 or fewer days at any dose, no washout period required as long as they discontinue prior to starting study therapy); NOTE: topical treatment may have been given for prior existence of cutaneous lymphoma that has since become systemic PTCL; however, these topical therapies should be stopped at time of registration
For Part E (LY2835219 + exemestane + everolimus): The participant must have received prior systemic endocrine therapy with at least one nonsteroidal aromatase inhibitor (anastrozole, letrozole) for metastatic disease and may be receiving ongoing therapy with either exemestane or exemestane + everolimus.
Concurrent non-protocol-specified anti-tumor therapy (e.g., chemotherapy, other targeted therapy, topical therapy such as 5-fluorouracil or imiquimod, radiation therapy, surgery, or photodynamic therapy\r\n* For patients with multiple cutaneous BCCs at baseline that are not designated by the investigator as target lesions, treatment of these non-target BCCs with surgery may be permitted but must be discussed with data coordinator prior to any surgical procedure
For patients with LABC, no prior therapy is allowed
Glucocorticoid therapy allowed.
Subjects must have recovered from all toxicity associated with previous chemotherapy, targeted therapy, experimental therapy, biological therapy, immuno-oncology therapy, surgery, radiotherapy, or other locoregional therapy. (Exception: Subjects may enter with continuing alopecia.) The following intervals must elapse between end of last treatment and receiving the first dose of SM08502:
Require concomitant chemotherapy, radiation therapy, or immunotherapy. Hydroxyurea is allowed up to the evening before starting (but not within 12 hours) of starting Induction therapy.
At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives\r\n* Exceptions:\r\n** There is no time restriction with regard to prior intrathecal chemotherapy (including [incl.] steroids) provided there is complete recovery from any acute toxic effects of such\r\n** Subjects receiving hydroxyurea may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis\r\n** Subjects who are on standard ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy is discontinued at least 1 week prior to apheresis\r\n** Subjects receiving steroid therapy at physiologic replacement doses (=< 5 mg/day of prednisone or equivalent doses of other corticosteroids) only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis\r\n** For radiation therapy: radiation therapy must have been completed at least 3 weeks prior to enrollment, with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation port
more than one sequential second generation AR-directed therapy
No prior Y90 radioembolization for HCC is permitted; therapies below are allowed but must be completed 4 weeks prior to baseline scan:\r\n* Prior transarterial embolization (TAE) or transarterial chemoembolization (TACE)\r\n* One treatment of stereotactic body radiation therapy (SBRT)\r\n* Liver resection\r\n* Ablation therapy
Patients who are candidates for local salvage therapy must have had this option pursued or discussed; and the patient must have either declined salvage therapy or was deemed not to be a candidate for salvage therapy
Prior radiation therapy to the liver including 90Y , I131 based loco regional therapy. Prior loco regional therapy, including resection, based on other technology for ICC, if any, must have been completed at least 4 weeks prior to baseline imaging.
Prior isotope therapy with strontium-89, samarium or RAD223
Patients must be receiving optimal therapy for their extracranial disease according to local practice at each center. Patients may continue on systemic therapy while receiving TTFields.
Duration of prior HMA therapy ? 9 months and/or total ? 9 cycles of prior HMA therapy in ? 12 months
Limited prior therapy, including hydroxyurea for 72 hours or less, systemic glucocorticoids for one week or less, one dose of vincristine, and one dose of intrathecal chemotherapy
Patients must be weaned off prednisone and be off therapy for >= 1 week prior to starting therapy
Any therapy including chemotherapy (e.g., docetaxel) or biological therapy (e.g., vaccine, immunotherapy) for the treatment of castration-resistant prostate cancer. Previous treatment with flutamide, steroidal anti-androgens, androgens, estrogens, bicalutamide, nilutamide, or 5-? reductase inhibitor is permitted.
Subject must be non-refractory to bortezomib (Refractory is defined: progression of disease while receiving bortezomib therapy or within 60 days of ending bortezomib therapy).
Failed at least one trial of immunosuppressive therapy (IST) by being refractory or having relapsed. IST could have included ATG based regimens, calcineurin inhibitors and/or other higher dose therapy directed at the treatment of primary SAA.
Participants who have had prior local regional therapy including radiation therapy, transarterial therapy, or ablative therapy
Receiving glucocorticoid therapy and calcineurin therapy or glucocorticoid therapy alone for cGVHD at study entry. Subjects on calcineurin therapy only, without glucocorticoid therapy, are not eligible. Subjects also receiving other therapies thought not to be immunosuppressive (such as extracorporeal photopheresis; ECP), will be considered for enrollment in this study on a case-by-case basis.
For patients who have received prior radiation, cryotherapy, radiofrequency ablation, TheraSphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:\r\n* 28 days have elapsed since that therapy\r\n* Lesions that have not been treated with local therapy must be present and measureable
Prior infusion of a genetically modified therapy
Prior MRI results dated within 120 days prior to ablation.
Prior therapy with afatinib
Biopsy-proven, measurable, stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy (Note: extracorporeal photopheresis will be considered a systemic therapy for this study)
Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 14 days should have elapsed from the last day of radiation; NOTE: prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
There is no waiting period for participants who relapse while receiving frontline therapy and are free from side effects attributable to such therapy
Prior anti-angiogenic therapy, including thalidomide and oral cyclophosphamide, is permitted
Patients receiving full dose anticoagulative therapy
Prior radiation therapy is allowed but there should not be overlap with the prior high dose regions unless approved by the protocol directors
No prior purine analog therapy except up to 1 prior course of either cladribine or pentostatin
ALL patients refractory to liposomal vincristine as defined by progression while on therapy or relapse within 3 months of completion of therapy with liposomal vincristine
Prior immuno-oncology therapy
Prior systemic therapy is allowed after diagnosis of brain metastases provided that restaging MRI shows measurable intracranial disease
Must receive optimal therapy for extracranial disease and may continue on systemic therapy during TTF administration
Prior therapy with etoposide and cyclophosphamide is allowed
Prior therapy with LMB-100
Recipient of CAR-T cell therapy outside of this protocol.
Failure to recover to grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, immunotherapy, and/or experimental therapy, with the exception of: alopecia, grade =< 2 peripheral neuropathy, grade =< 2 cetuximab-related rash or other skin changes, hypomagnesemia (acceptable values detailed below), hypokalemia (acceptable values detailed below), and the acceptable hematologic values summarized above; a washout period of 2 weeks from prior cetuximab is required; a washout period of 3 weeks from any prior cytotoxic chemotherapy, targeted therapy, immunotherapy or investigational drug is required
Hepatic intra-arterial embolization or peptide receptor radionuclide therapy (PRRT) within 4-8 weeks; cryoablation, radiofrequency ablation or trans-arterial chemoembolization of hepatic metastases within ? 4 weeks of study enrollment
Biopsy-proven, measurable, stage IB-IVB relapsed or refractory cutaneous T-cell lymphoma after 2 lines of skin-directed therapy or one prior line of systemic therapy\r\n* Note: extracorporeal photopheresis will be considered a systemic therapy for this study
Patients with high-risk MDS, and chronic myelomonocytic leukemia (CMML) with bone marrow blasts between 10% and 20%, relapsed or refractory to prior hypomethylating agent (HMA) therapy, defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or relapse after prior response to HMA therapy
Subjects receiving systemic steroids, nitrogen mustard, psoralen UVA radiation therapy (PUVA), narrow band UVB light therapy (NB-UVB) or carmustine (BCNU) or other systemic therapies for CTCL within 3 weeks of enrollment.
There is no limitation of amount or the type of prior therapy or drugs
Chimeric Antigen Receptor (CAR)-T cell therapy.
At least 4 weeks away from any previous antineoplastic or investigational agent; patients may receive hydroxyurea or glucocorticoids for suppression of leukocytosis, but these must be stopped at least 24 hours (h) prior to initiation of therapy
No prior cytotoxic regimens are allowed for this malignancy. Patients may not have had prior chemotherapy or prior radiation therapy to the ipsilateral breast for this malignancy. Prior bis-phosphonate therapy is allowed
(Arm B only): Subject must be relapsed or refractory to prior hypomethylating agent therapy, defined as prior receipt of 6 cycles of HMA therapy with failure to attain a response, or relapse after prior response to HMA therapy
No prior genetically modified cell therapy that is still detectable or virotherapy allowed
Hormone replacement therapy or vaginal estrogen therapy, DHEA, or biosynthetics within 6 weeks prior to enrollment
Receiving, or previously received, any systemic chemotherapy, or investigational agent for HCC\r\n* Note: prior surgical resection with recurrence, or palliative local therapy (including transcatheter arterial chemoembolization [TACE], Y-90 resin microspheres, etc.) would not exclude trial participation, but must have been performed at least 6 months prior to enrollment
Prior therapy with a compound of the same mechanism as PF-05082566 (immunomodulation of 4-1BB)
Candidate for potentially curative antibiotic therapy for gastric mucosa-associated lymphoid tissue (MALT); (gastric MALT lymphoma patients with stage I/II helicobacter [H.] pylori positive lymphoma must fail therapy with H.-pylori directed therapy before being considered for this study)
No prior genetically modified cell therapy that is still detectable >= 5% in the peripheral blood
No prior virotherapy allowed
At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives\r\n* Exceptions:\r\n** There is no time restriction with regard to prior intrathecal chemotherapy (including [incl.] steroids) provided there is complete recovery from any acute toxic effects\r\n** Subjects receiving hydroxyurea may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis\r\n** Subjects who are on standard ALL maintenance type chemotherapy (vincristine, 6-mercaptopurine or oral methotrexate) may be enrolled provided that chemotherapy is discontinued at least 1 week prior to apheresis\r\n** Subjects receiving steroid therapy at physiologic replacement doses (>= 5 mg/day of prednisone or equivalent doses of other corticosteroids) only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis\r\n** For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to enrollment, with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the subject has measurable/evaluable disease outside the radiation port
Received at least one prior line of cancer therapy for the treatment of NSCLC; this should include at least one of the following: platinum (carboplatin or cisplatin) doublet chemotherapy (acceptable combinations include: paclitaxel, docetaxel, abraxane, pemetrexed, gemcitabine, vinorelbine, or etoposide), anti-PD1/PDL1 therapy (pembrolizumab, nivolumab, or atezolizumab), or appropriate targeted therapy in patients with activating EGFR (osimertinib, erlotinib, gefitinib, or afatinib), ALK (alectinib, crizotinib, ceritinib, brigatinib, or loralatinib), or ROS-1 (crizotininb or entrectinib) alterations; therapy may be given as monotherapy or in combination with other cancer therapy (e.g. bevacizumab, ipilumimab)
No prior MM-directed therapy except for dexamethasone (up to 160 mg) and/or bortezomib (up to 5.2 mg/m^2) and/or cyclophosphamide up to 1000 mg/m^2 administered for management of acute manifestations of MM (hypercalcemia, renal impairment, pain) for no longer than 4 weeks prior to enrollment. If subject received any prior therapy, pretreatment parameters necessary for disease characterization and response assessment must be available
Participants may have had prior chemotherapy, targeted biological therapy (i.e. sorafenib), surgery, transarterial chemoembolization (TACE), radiofrequency ablation, or cryosurgery for their disease as long as the prior therapy occurred more than 3 weeks before the first radiation treatment; patients may not have had prior liver directed radiation, including radioembolization
131I therapy < 6 months prior to initiation of therapy on this protocol; a diagnostic study using < 10 mCi of 131I is not considered 131I therapy
Currently on therapy for active chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria); prophylactic therapy is allowed
Prior anti-tumoral radionuclide therapy with unsealed sources; prior therapy with sealed radioactive sources such as brachytherapy will be allowed
Patients may be on somatostatin analogue therapy (e.g. but not only limited to sandostatin or lanreotide therapy); however, therapy with somatostatin analogues should not be initiated or altered within 3 months of study enrollment; patients on short term octreotide may have dose held for 24 hours prior to Lu-177-DOTATATE therapy; those on long acting octreotide therapy will receive treatment at 1 to 5 days prior to their next cold octreotide dose, in order to prevent competition for the receptor
Allowed prior therapy:\r\n* Newly diagnosed DLBCL and low grade B cell lymphoma: No prior therapy is allowed except steroids equivalent to maximum of prednisone 20 mg once daily for maximum of seven days prior to registration\r\n* Relapsed/refractory low grade B cell lymphoma (only allowed in phase I): A minimum and maximum of one line of prior non-anthracycline containing therapy is allowed; prior localized radiation therapy is not considered a line\r\n* For patients who have had prior chemotherapy or immunotherapy, at least 2 weeks must have elapsed between last dose and initial dose of RCHOP-selinexor; for patients treated with radio-immunotherapy, at least 12 weeks
Patients must not have had leukemia therapy for 14 days prior to starting palbociclib. However, patients with rapidly proliferative disease may receive hydroxyurea as needed until 24 hours prior to starting therapy on this protocol and during the first cycle of study
Must have received at least one but not more than two prior anti-angiogenic therapy regimens (including, but not limited to, sunitinib, sorafenib, pazopanib, axitinib, tivozanib, and bevacizumab) in the advanced or metastatic RCC setting; prior cytokine therapy (eg, IL-2, IFN-alpha), vaccine therapy, or treatment with cytotoxics is also allowed
No prior therapy, or limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy (e.g., to the mediastinum, head and neck, orbit, etc.) and one dose of intrathecal chemotherapy
Patients with prior known toxicity attributed to PD-1 or PDL-1 directed therapy, which led to discontinuation of these agents, will be excluded from the PDR001 containing arms of the study.
Patients with prior known toxicity from IL-17A directed therapy, which led to discontinuation of the study treatment, will be excluded from CJM112 containing arms of the study.
Patients with plans to receive other concomitant local therapy (including standard fractionated radiotherapy and surgery) or other systemic therapy (including chemotherapy, target therapy and other type of immunotherapy or investigative agents) while on this protocol, except at disease progression, are not eligible
Treatment with the following within the 4 weeks prior to the screening visit: radiotherapy, intralesional therapy; laser therapy surgery (other than biopsy) to the target area, local hyperthermia, levulinic acid, 5-fluorouracil, high potency corticosteroids (including systemic steroids), retinoids, diclofenac, hyaluronic acid, imiquimod;
>= 2 months since last therapy for HSIL
Prior or ongoing systemic therapy for prostate cancer including, but not limited to:\r\n* Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)\r\n* CYP-17 inhibitors (e.g. ketoconazole)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. enzalutamide, ARN-509)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)\r\n* Note: may be enrolled if has recently initiated hormone therapy (< 90 days duration); in the event that hormone therapy was initiated prior to study enrollment, the clock for 1 year of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment
Non-resectable, recurrent, or metastatic well- or moderately-differentiated gastroenteropancreatic neuroendocrine tumor (GEP-NETs) with disease progression within the last 12 months; (patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of > 20% in the size; prior local therapy must be completed at least 4 weeks prior to the baseline scan)
Patients receiving prior therapy with HCQ
Patients must have failed at least one regimen of chemo or radiation therapy; NOTE: There is no limit to the number or types of prior therapy
Use of experimental drug therapy for myelofibrosis, or any other standard drug (eg, danazol, hydroxyurea, etc) with the exception of ruxolitinib within 6 months of starting study (combination) therapy and/or lack of recovery from all toxicities from previous therapy (except ruxolitinib) to Grade 1 or better
Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JCAR017 treatment in this protocol for subjects receiving retreatment
Patients must discontinue antiandrogen therapy (i.e., flutamide, bicalutamide, nilutamide) for at least 4 weeks prior to registration with no evidence of a falling PSA after washout
Completion of major surgery, chemotherapy, targeted therapy (such as everolimus or experimental agents or radiation within 14 days prior to starting investigational drug or has not recovered from major side effects; there is no required washout period from completion of prior anti-estrogen therapy (either scenario) or prior CDK 4/6 inhibitor (if scenario 2) to initiation of ribociclib/placebo and anti-estrogen on trial
Prior treatment\r\n* Phase I: exposure to 2-3 prior lines of therapy or no therapeutic options\r\n* Phase II: previously untreated for symptomatic MM\r\n* EXCEPTION: =< 7 days with pulse steroids or localized radiation therapy, without curative intent, for a myeloma-related complication prior to registration is allowed, as considered necessary by the treating physician
Previously untreated for myeloma or have received no more than one cycle of any treatment regimen; NOTE: Prior radiation therapy for the treatment of solitary plasmacytoma is permitted; prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
Chemotherapy/systemic therapy, radiotherapy, immunotherapy or surgery =< 21 days prior to registration or kinase inhibitor therapy =< 14 days prior to registration or failure to recover from toxicities (to grade 1 or below) from treatment; NOTE: concurrent therapy with octreotide is allowed providing that tumor progression on this therapy has been demonstrated; concurrent therapy with bisphosphonates (e.g. zoledronic acid) or denosumab is also allowed; NOTE: an unlimited number of prior chemotherapeutic or biologic therapies for malignant pheochromocytoma or paraganglioma is permitted; this includes prior anti-angiogenesis therapies such as tyrosine kinase inhibitors
Completion of local therapy, such as radiation, surgical resection, injectable immunebased therapy, or topical pro-inflammatory agent, 21 days prior to first dose of protocol therapy.
Prior interferon or interleukin-2 therapy is NOT allowed
Must have completed any systemic therapy at least one week prior to planned start of SBRT (two weeks preferred), and must have no plans to initiate systemic therapy for at least one week following end of SBRT (two weeks preferred)
Time interval for last local therapy (radiofrequency ablation, percutaneous ethanol injection, radiotherapy, transarterial chemoembolization) more than 4 weeks prior to registration
Prior antiestrogen therapy
Patient must have failed at least one prior therapy
Patients are excluded if they have had prior hepatic arterial embolization therapy
Patients must have either:\r\n* Symptomatic multiple myeloma who have responded to prior induction or salvage chemotherapy (i.e. chemosensitive disease): patients who are receiving high-dose melphalan and AHCT as part of their initial therapy require at least a partial response (PR) as defined by the International Myeloma Working Group uniform response criteria for MM; patients who are receiving high-dose melphalan and AHCT as part of salvage therapy require at least a minor response to their last line of therapy to document chemosensitive disease; there is no limit on the number of prior regimens received by the patient; OR\r\n* Light chain (AL) amyloidosis who may be newly diagnosed or previously treated
Prior thermal ablative therapy for prostate cancer (e.g. high-intensity focused ultrasound [HIFU] or cryoablation)
Patients receiving cytotoxic agent as immunomodulatory therapy for a non neoplastic indication (e.g. methotrexate for rheumatoid arthritis) and who are unable to discontinue such agents within 2 weeks prior to starting treatment
Need or plans for concomitant antineoplastic therapy (including surgery, cryotherapy, radiofrequency ablation, chemo-embolization, conventionally fractionated radiotherapy, stereotactic body radiation therapy, and hepatic artery chemotherapy) for the protocol treated lesions except at progression; adjuvant systemic therapy before and after the protocol therapy, and surgery or other ablative therapy is allowed for lesions appearing after enrollment to this protocol is allowed; at least 4 weeks must have passed since the last directed intervention to the protocol-treated lesion
Patients have a history of prior therapy with carboplatin
Prior conventional antitumor therapy, other than steroids, radiation therapy (RT) or TMZ therapy given for glioblastoma
Prior or ongoing systemic therapy for prostate cancer including, but not limited to:\r\n* Hormonal therapy (for example [e.g.] leuprolide, goserelin, triptorelin, degarelix)\r\n* Cytochrome P450 (CYP)-17 inhibitors (e.g. ketoconazole)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. enzalutamide, apalutamide)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)
Any of the disease stages listed below\r\n* Stage IB disease that meets ALL of the following criteria:\r\n** Plaque disease (ie,T2b staging)\r\n** Diffuse skin involvement with indication for TSEB (plaque disease with or without patches)\r\n** Not appropriate for treatment with focal therapies\r\n** One prior course of low-dose TSEB or one prior course of systemic chemotherapy regimens (excluding brentuximab)\r\n* Stage IIA, IIB, or IIIA that meets ONE or BOTH of the following criteria:\r\n** Patient is a candidate for treatment with low-dose TSEB\r\n** Patient is a candidate for systemic therapy\r\n* IIIB or IVA disease requiring systemic therapy\r\n* Transformed cutaneous T-cell lymphoma (CTCL)
No prior antineoplastic drug therapy for at least 14 days, with the exception of hydroxyurea, prior to starting OTS167. Patients with rapidly proliferative disease may continue to receive hydroxyurea.
No prior antineoplastic drug therapy for at least 14 days, with the exception of hydroxyurea, prior to starting OTS167. Patients with rapidly proliferative disease may continue to receive hydroxyurea.
Patients should have discontinued therapy with imatinib, dasatinib, nilotinib, ponatinib, omacetaxine or other anti-leukemia therapy (except hydroxyurea) >= 48 hours prior to start of study therapy and recovered from any toxicity due to these therapies to grade =< 1; hydroxyurea may be received up to the time of enrollment and for the first 6 weeks of study treatment if necessary
Receipt of any anti-cancer therapy within 14 days prior to C1D1, with the exception of hydroxyurea or anagrelide (within 24 hours), TKI (within 1days), or a single dose of cytarabine (for proliferative disease)
Must have received at least one prior anti-angiogenic therapy (or inability to tolerate, as above) in the advanced or metastatic setting; prior cytokine therapy (eg, IL-2, IFN-alpha), vaccine therapy, or treatment with cytotoxics is also allowed but not any other drug specifically targeting T-cell co-stimulation or checkpoint pathways
Not pregnant, or taking effective contraception before rapamycin therapy, during therapy and for 12 weeks after discontinuation of therapy
Patients having prior therapy with Laser Induced Thermal Therapy (LITT) is allowed, but at least 21 days must have elapsed from last LITT, with recovery from all LITT-related toxicities to Grade 1 or less and subsequent histologic documentation of recurrence
Prior therapy with lomustine
Prior systemic therapy for prostate cancer including, but not limited to:\r\n* Hormonal therapy (e.g. leuprolide, goserelin, triptorelin, degarelix)\r\n* CYP-17 inhibitors (e.g. ketoconazole)\r\n* Antiandrogens (e.g. bicalutamide, nilutamide)\r\n* Second generation antiandrogens (e.g. abiraterone, enzalutamide)\r\n* Immunotherapy (e.g. sipuleucel-T, ipilimumab)\r\n* Chemotherapy (e.g. docetaxel, cabazitaxel)\r\n* Note: may be enrolled if hormone therapy was recently initiated of any kind (< 90 days duration); in the event that hormone therapy was initiated prior to study enrollment, the clock for 1 year of androgen deprivation would begin at the time of therapy initiation, rather than at study enrollment
Subjects must be willing to refrain from blood donations during study drug therapy and for 8 weeks after therapy
For patients who have received prior radiation, cryotherapy, radiofrequency ablation, therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met:\r\n* 28 days have elapsed since that therapy\r\n* Lesions that have not been treated with local therapy must be present and measurable
Prior therapy with TAS-102
Any prior arterial liver-directed therapy, including transarterial chemoembolization (TACE), arterial embolization (TAE), and 90Y radioembolization
Patients with malignant solid tumors must have relapsed after or failed to respond to frontline therapy and there must be no other known curative therapies available. Patients with desmoid fibromatosis must have relapsed after or failed to respond to at least one prior line of therapy, and in the opinion of the treating physician surgical resection of the tumor must not be possible without an amputation or other surgery predicted to result in an unacceptable functional deficit.
Chemotherapy, immunotherapy, hormonal therapy, biologic therapy, or any other anticancer therapy or investigational medicinal product (IMP) within 28 days of first trial drug intake for Phase Ia subjects, and any prior therapy for Phase Ib subjects. For subjects with rapidly growing tumors localized in the head and neck region or thorax where the treating physician cannot wait for 28 days, inclusion may take place if there is no residual toxicity from previous treatment (maximum CTCAE Grade 1)
Completing SoC adjuvant therapy per NCCN guidelines to include chemotherapy, radiation therapy, and/or biologic therapy as clinically indicated. (Consent #2 should be signed as close to completion of SoC as possible but may overlap completion by up to one month.)
Maintenance therapy during the first platinum-free interval is allowed; however, the last dose must have been at least 21 days prior to Randomization. No cancer vaccine therapy is allowed.
Prior CAR therapy or other genetically modified T cells
CAR-T infusion or other cellular therapy within 30 days
Unable to tolerate gastrointestinal prophylaxis therapy with sucralfate while on pre-phase and remission induction therapy; or severe pre-existing gastrointestinal (GI) disorder that requires peptidylprolyl isomerase (PPI) or histamine H2 (H2) receptor antagonist therapy be uninterrupted
For patients with type II diabetes receiving only oral anti-hyperglycemic therapy (patients receiving insulin are not eligible), the following are required at screening:\r\n* HbA1c < 8.5 % or IFCC < 69.4 mmol/mol\r\n* Stable regimen of oral anti-hyperglycemic therapy without insulin usage for at least 3 weeks prior to first study treatment\r\n* Fasting plasma glucose levels =< 160 mg/dL (8.88 mmol/L) and no hypoglycemia (blood sugar [BS] < 60) during home monitoring for at least 1 week prior to study entry
ARM 1 AND 2 FRONT LINE OLDER COHORT: Patients age 65 years and above with previously untreated AML (>= 20% blasts) who are unfit for or decline standard induction therapy; prior therapy with hydroxyurea, biological or targeted therapy (e.g. FLT3 inhibitors, other kinase inhibitors), or hematopoietic growth factors is allowed, however prior therapy with chemotherapy agents for the disease under study is not allowed; patients may have received one dose of cytarabine (up to 2 g/m2 administered at presentation for control) of hyperleucocytosis; the frontline cohort of vidaza+nivolumab+ipilimumab and vidaza+nivolumab will be open simultaneously and we will enroll alternately to these two frontline protocols with close monitoring for futility and as specified in the predefined statistical futility and toxicity stopping rules
Patients for whom busulfan/melphalan consolidation therapy following treatment with 131I-MIBG is planned
Patients for who CEM (carboplatin, etoposide, melphalan) therapy is administered within 30 days prior to 131I-MIBG therapy or for whom this therapy is planned within 30 days following administration of 131I-MIBG
Prior treatment of B-NHL with radiation therapy, non-standard systemic therapy, or antibiotics (in cases of MZL) within 21 days of the first dose of ixazomib
Patients receiving prior therapy with RGF, VOR, and/or HCQ
No prior genetically modified cell therapy that is still detectable or prior virotherapy
Prior local therapy, such as surgery, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment; local therapy must have been completed at least 4 weeks prior to the baseline scan
Persistent or recurrent adenovirus infection or disease despite at least 7 days of standard therapy or failure of therapy as described below or if unable to tolerate standard therapy. Standard therapy is defined as antiviral therapy with cidofovir or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function. i. Adenovirus infection: defined as the presence of adenoviral positivity as detected by polymerase chain reaction (PCR) or culture from ONE site, such as stool or blood or urine or nasopharynx. ii. Adenovirus disease: defined as the presence of adenoviral positivity as detected by PCR, Direct fluorescent assay (DFA) or culture from two or more sites such as stool or blood or urine or nasopharynx. iii. Failure of therapy: defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease as measured by PCR (or any other quantitative assay) after 7 days of antiviral therapy.
Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration unless the patient has recovered from the nadir of the previous treatment to a level that meets the inclusion eligibility criteria of this protocol
Prior therapy with neural stem cells
Prior treatment with fractionated radiation therapy (up to 60 Gy) is an eligibility criterion, however there should not have been a second course of fractionated radiotherapy to the supratentorial area
Persistent disease after at least a partial response to frontline therapy (i.e. patient has had at least a partial response to frontline therapy but still has residual disease by MIBG, CT/MRI, or bone marrow)
Prior therapy with fenretinide and/or fenretinide + ketoconazole is allowed if no DLT's were experienced. Prior therapy with other retinoids
Cytoreduction therapy with plasmapheresis or hydroxyurea acceptable
Adenovirus: Treatment of persistent adenovirus infection or disease despite standard therapy; standard therapy is defined as antiviral therapy with cidofovir^13 or an alternative antiviral agent if patient will not tolerate cidofovir therapy because of poor renal function\r\n* Adenovirus infection: defined as the presence of adenoviral positivity as detected by PCR or culture from ONE site such as stool or blood or urine or nasopharynx\r\n* Adenovirus disease: defined as the presence of adenoviral positivity as detected by PCR, direct fluorescent antibody (DFA) or culture from two or more sites such as stool or blood or urine or nasopharynx\r\n* Failure of therapy: defined as a rise or a fall of less than 50% in viral load in peripheral blood or any site of disease (as measured by PCR or any other quantitative assay) after 7 days of antiviral therapy
PHASE I and II -- Administration of any antineoplastic therapy within at least 4 weeks (cytotoxic chemotherapy) or 2 weeks (biological and targeted therapy; hypomethylating agents are considered to be biological therapy) of that therapy of the first MEK 162/MEK 162 dose; except the use of hydroxyurea which can be administered up to 5 g/day up to 24 hours before the initiation of the study drug
Inclusion Criteria\n\n        -Male or female patients ?18 years of age who present with one of the following:\n\n        LGH447 monotherapy arm\n\n          -  Refractory/Relapsed AML following no more than 2 prior therapies, or in previously\n             untreated AML patients who are not candidates for standard therapy.\n\n          -  High and very high risk MDS according to the revised International Prognostic Scoring\n             System (rIPSS) who have failed prior therapies, such as azacitidine and decitabine\n\n          -  Patients with rIPSS score of > 4.5\n\n        LGH447 and midostaurin combination arm\n\n          -  Refractory/Relapsed AML following no more than 2 prior therapies, or in previously\n             untreated AML patients who are not candidates for standard therapy. AML patients may\n             have either FLT3 wild type or FLT3-ITD/TKD mutant disease, and FLT3 mutation status\n             needs to be defined at study entry.\n\n               -  For AML patients, peripheral blast counts < 50,000 blasts/mm3\n\n               -  For MDS patients;\n\n          -  Platelet count > 25,000/mm3\n\n          -  Neutrophils > 500/mm3\n\n          -  Blood transfusions are allowed to maintain clinically adequate hemoglobin and\n             hematocrit levels\n\n               -  Patients with active central nervous system (CNS) disease are eligible to\n                  participate and may be treated concurrently with intrathecal (or intra Ommaya)\n                  chemotherapy\n\n               -  Patients who are maintained on prophylactic antibiotics are eligible to\n                  participate as long as agents comply with the list of approved concomitant\n                  medications\n\n               -  Performance status ? 2\n\n               -  Meet other lab criteria\n\n        Exclusion Criteria\n\n          -  Systemic antineoplastic therapy (including unconjugated therapeutic antibodies and\n             toxin immunoconjugates) or any experimental therapy within 7 days or 5 half-lives,\n             whichever is longer, before the first dose of LGH447 monotherapy or LGH447 in\n             combination with midostaurin\n\n          -  Radiotherapy with a wide field of radiation within 28 days or radiotherapy with a\n             limited field of radiation for palliation within 7 days of the first dose of LGH447\n             monotherapy or LGH447 in combination with midostaurin\n\n          -  Patients who received CNS irradiation for meningeal leukemia, except if radiotherapy\n             occurred > 3 months previously\n\n          -  Major surgery within 4 weeks before the first dose of LGH447 monotherapy or LGH447 in\n             combination with midostaurin\n\n          -  Ongoing therapy with corticosteroids greater than 10 mg of prednisone or its\n             equivalent per day. Inhaled and topical steroids are permitted\n\n          -  Patients who are currently receiving hydroxyurea to control peripheral blood leukemic\n             blasts and cannot be discontinued for at least 48 hours prior to obtaining PD\n             biomarkers at screening/baseline and during the study\n\n          -  Patients who are currently receiving treatment with prohibited medication and that\n             cannot be discontinued at least one week prior to the start of treatment with LGH447\n             monotherapy or LGH447 in combination with midostaurin\n\n          -  Active infection requiring systemic therapy or other severe infection, including\n             pneumonia, within 2 weeks before the first dose of LGH447 monotherapy or LGH447 in\n             combination with midostaurin\n\n          -  Known human immunodeficiency virus (HIV) positive\n\n          -  Corrected QT interval (QTc) of > 450 milliseconds (ms) in males and > 470 milliseconds\n             (ms) in females on baseline electrocardiogram (ECG) (using corrected QT interval using\n             Fridericia [QTcF] or local standards).\n\n          -  Uncontrolled cardiovascular condition, including ongoing cardiac arrhythmias,\n             congestive heart failure, angina, or myocardial infarction within the past 6 months\n\n          -  Pregnant or nursing
Receipt of Gliadel therapy
Patients who have a history of listeriosis prior ADXS11-001 therapy
If prior therapy with gamma knife or other focal high-dose radiation, must have subsequent histologic documentation of local relapse, or relapse with new lesion outside the irradiated field
All prior therapy must have been completed at least 21 days prior to enrollment; no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
RANDOMIZED PHASE II (ARMS K AND L): All prior therapy must have been completed at least 21 days prior to enrollment (6 weeks for nitrosoureas or mitomycin C); no concomitant anti lymphoma therapy, including systemic corticosteroids for the purpose of treatment of lymphoma are allowed; topical steroids are allowed
For Phase I and II: Patients must have been off chemotherapy for 2 weeks prior to entering this study, unless there is evidence of rapidly progressive disease, and must have recovered from the toxic effects of that therapy to at least grade 1. Use of hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and for the first four weeks on therapy. The additional days of Hydrea after 28 is permitted as clinically indicated, on case by case basis after discussion with the PI. Other agents given transiently with the intention to control rapid proliferation such as 1-2 doses of single agent ara-C or few doses of sorafenib are also allowed.
INCLUSIONS FOR CAR-T CELL THERAPY
EXCLUSIONS FOR CAR-T CELL THERAPY
Patients with previously untreated AML (by the World Health Organization [WHO] criteria, i.e. >= 20% blasts); prior biologic therapies (such as growth factors) and targeted therapies administered for the treatment of prior myelodysplastic syndrome are allowed, with the exception of hypomethylating agents 5-azacytidine or decitabine; patients must have been off such therapy for 1 week prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease; hydroxyurea, and a single dose of cytarabine up to 3 g/m^2, is permitted for control of counts prior to treatment
Stage IIIB/C patients must have refused, be ineligible for, or have failed at least one standard of care regional therapy (isolated limb perfusion or infusion) or one non-vaccine based systemic therapy (such as, high dose interleukin [IL]-2, dacarbazine/temozolomide, ipilimumab, or participation in a clinical trial); patients who are BRAF V600E mutation positive need to have failed, refused, or be ineligible for at least 2 lines of therapy (vemurafenib plus one other regimen)
For cohort of patients that are already on ruxolitinib therapy: on therapy with ruxolitinib for at least for 6 months, and on stable dose for last 2 months, before starting therapy with sotatercept
Prior therapy with any hypoxic cytotoxin (hypoxia-targeting drugs).
PHASE I: Patients may have had treatment for any number of prior relapses; relapse is defined as progression following initial therapy (i.e. surgery and radiation +/- chemotherapy [chemo] if that was used as initial therapy)
PHASE II: Patients may have had treatment for no more than 1 prior relapse (i.e. failed 2 lines of treatment-initial therapy and therapy for first relapse) at 2nd relapse, treatment per BTTC09-01 is an option; relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy); the intent therefore is that patients had no more than 2 prior therapies (initial and treatment for 1 relapse); if the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered as 1 relapse; for patients who had prior therapy for a low-grade glioma, the surgical diagnosis of a high-grade glioma will be considered the first relapse
Recent prior therapy: systematic chemotherapy less than 2 weeks prior to infusion; exceptions:\r\n* There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such\r\n* Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment\r\n* Subjects receiving steroid therapy at physiological replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to subject starting apheresis or treatment\r\n* Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met; cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion
Phase II IMT naive cohorts: Patients have not received systemic cytotoxic or immune-based therapy for advanced melanoma. BRAF and/or MEK inhibition therapy is acceptable before immunotherapy where clinically indicated. Other systemic cytotoxic or targeted therapy in the advanced setting is not permitted in this subset
RAI-avid lesion on a radioiodine scan (a diagnostic, post-therapy, or post-ablation scans) performed =< 24 months prior to registration, which suggests that therapy with 131I is justifiable in the judgment of the investigator
131I therapy =< 6 months prior to registration; Note: 131I administered solely for diagnostic purposes is not considered 131I therapy
Prior therapy with romidepsin
Prior intrapleural therapy (except pleurodesis) or intrapleural therapy at the time of P/D (i.e.: intrapleural chemotherapy, photodynamic therapy, intrapleural betadine)
Previous systemic chemotherapy or non-radiation local therapy (such as surgery, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) is allowed; the lesion must however have shown criteria of progression based on RECIST; local therapy must be completed at least 4 weeks prior to the baseline scan; this is to create a safer treatment environment and to help determine the effect of treatment by SBRT alone; patients will be allowed to go onto appropriate systemic therapy, as determined by their medical oncologist, 2 weeks following delivery of SBRT
Patients can have extra-hepatic disease, provided the hepatic disease is the highest burden, the extra-hepatic disease is low burden and potentially treatable with surgery, ablative radiation therapy, or United States (US) Food and Drug Administration–approved first- or second-line systemic therapy regimens
Corticosteroid therapy and endocrine replacement therapy (L-thyroxine, testosterone, estrogen, desmopressin acetate [DDAVP]) are permissible; any patient already receiving human growth replacement therapy should discontinue this prior to commencing chemotherapy, and should not restart until 3 years from diagnosis
Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation
Radiopharmaceutical therapy (eg, radiolabeled antibody, 131I-metaiodobenzylguanidine): ?42 days after systemically administered radiopharmaceutical therapy.
Have documented evidence of progressive disease (PD) on or after their last regimen as defined by IMWG criteria. All participants must have received between 1 to 3 prior therapies for MM (a prior therapy is defined as 2 or more cycles of therapy given as a treatment plan for MM [eg, a single-agent or combination therapy or a sequence of planned treatments such as induction therapy followed by autologous stem cell transplant (SCT) and then consolidation and/or maintenance therapy]).
Patients with intermediate-1 or higher risk MDS who have failed therapy with a hypomethylating agent, or have failed lenalidomide therapy if harboring a 5q-chromosomal deletion.
Plans for the patient to receive other concomitant antineoplastic therapy (including standard fractionated radiotherapy, chemotherapy, biological therapy, vaccine therapy, and surgery) while on this protocol except at disease progression
Oral treatment with anti-infective therapy that has been administered less than one week prior to first dose in this trial.
Prophylactic anti-infective therapy, which is given without clinical symptoms is allowed.
thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) or aspirin over 165 mg daily or dual antiplatelet therapy;
are in relapse following an initial response and no more than 1 prior salvage therapy
failed primary induction therapy with no complete remission and for whom no other approved therapy is available, and no more than 1 prior salvage therapy
Subject has no prior anti-myeloma treatment therapy within 14 days prior to initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may have received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care, or radiation therapy as palliation for pain and/or spinal cord compression.
Patients with MF/SS must have failed at least 1 prior topical therapy (including steroids, nitrogen mustard, retinoids, phototherapy, photochemotherapy, radiation, and total skin electron beam); there is no upper limit for prior therapies
Prior TCN-PM therapy
Currently benefiting from the treatment with ruxolitinib alone, ruxolitinib plus background cancer therapy, or background cancer therapy alone, as determined by the investigator.
Able to access ruxolitinib and/or background cancer therapy outside of the clinical study.
202 Prior anti-cancer therapy as specified below: At least 3 half-lives from first dose of AMG 562 must have elapsed from any prior systemic inhibitory/stimulatory immune checkpoint molecule therapy (eg, ipilimumab, nivolumab, pembrolizumab, atezolizumab, OX40 agonists, 4-1BB agonists, etc). Other targeted anti-cancer therapy (chemotherapy, antibody therapy,molecular targeted therapy, steroids) within 14 days or 5 half lives (which ever is longer) prior to first dose of AMG 562. Patients requiring continued treatment due to aggressive disease may only be included if there is agreement by both the investigator and the Amgen Medical Monitor. Radiation therapy completed within 28 days prior to first dose of AMG 562. Autologous HSCT within six weeks prior to start of AMG 562 treatment.
207 Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy. Patient may be included if the treatment is discontinued more than 3 months prior to the first dose of AMG 562 at a low likelihood of relapse AND if there is agreement by both the investigator and the Amgen Medical Monitor.
Patients must have had at least one prior platinum-based chemotherapeutic regimen for management of primary disease; unlimited prior hormonal therapy, targeted therapy or antiangiogenic therapy will be permitted
Any local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed ? 4 weeks before first dose of study medication. Note: patients who received sole intrahepatic intra-arterial chemotherapy, without lipiodol or embolizing agents are not eligible.
Subjects with proven or suspected persistent bacteremia despite 72 hours of both systemic antibiotic therapy and lock therapy to which the infecting organism is susceptible;
Cancer-directed therapy within 2 weeks prior to starting treatment, with the exception of hydroxyurea, which is allowed to control white blood cell count. Hydroxyurea will be weaned as soon as clinically feasible.
Symptomatic metastatic brain or meningeal tumors unless the patient is >6 months from definitive therapy, has no evidence of tumor growth on an imaging study and is clinically stable with respect to the tumor at the start of study treatment. Also the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies).
Prior anti-GD2 therapy is not otherwise an exclusionary criteria unless it was given in combination with therapeutic 131I-MIBG.
The patient has no ongoing requirement for corticosteroids as therapy for CNS disease. Anti-convulsant therapy at a stable dose is permitted.
Has received prior therapy with IL-2 or other investigational systemic cytokine therapy signaling through a common gamma-chain cytokine receptor including IL-7, IL-15 or IL-21
Prior 131 I-MIBG therapy is excluded
Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) and have available TIL cultures for therapy
Patients who have received at least two cycles of initial systemic therapy and are within 2 to 12 months of the first dose. Mobilization therapy is not considered initial therapy.
Any skin-directed therapy within 14 days prior to day 1 of protocol therapy
Patients must not have received chemotherapy within 14 days of enrollment, with the two following exceptions: \r\n* Routine systemic maintenance therapy (e.g., Abelson murine leukemia viral oncogene homolog 1 [ABL] kinase inhibitor, methotrexate, 6-mercaptopurine, vincristine, etc.) and intrathecal/intraventricular therapy\r\n* Systemic therapy for the acute management of hyperleukocytosis or acute symptoms (e.g., corticosteroids, cytarabine, etc.)
No prior targeted treatment (tx) or anti-angiogenic therapy; patients may have received one line of prior therapy with octreotide, locoregional therapy; continuation of concurrent octreotide is allowed; patients will be maintained on octreotide (sandostatin) for the duration of their treatment
No prior therapy for this malignancy except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine (100-200 mg/m^2 per day for one week or less for hyperleukocytosis), and
To be performed within 28 days prior to day 1 of protocol therapy: Normal eye examination
Prior therapy with elotuzumab
Subjects must have completed their most recent drug therapy directed at multiple myeloma in the following timeframes:\r\n* Antitumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, retinoid therapy, hormonal therapy, or investigational agent) at least 21 days prior to cycle 1 day 1 (C1D1) AMG 232 + KRd\r\n* Corticosteroids at least 3 weeks prior to starting AMG-232 + KRd, except for a dose equivalent to dexamethasone of =< 4 mg/day\r\n* Autologous stem cell transplantation at least 12 weeks prior to starting AMG-232 + KRd\r\n* Allogeneic stem cell transplantation at least 24 weeks prior to starting AMG-232 + KRd, and these subjects must also NOT have moderate to severe active acute or chronic graft versus host disease (GVHD)
Patients who have received prior anti-GD2 therapy, including chimeric antigen receptor (CAR) T cells directed against GD2 antigen
Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-L-Ly or for any cancer diagnosis prior to the initiation of protocol therapy on AALL1231, with the exception of:\r\n* Steroid pretreatment: prednisone or methylprednisolone for =< 120 hours (5 days) in the 7 days prior to initiating induction chemotherapy or for =< 336 hours (14 days) in the 28 days prior to initiating induction chemotherapy; prior exposure to ANY steroids that occurred > 28 days before the initiation of protocol therapy does not affect eligibility; the dose of prednisone or methylprednisolone does not affect eligibility\r\n* Intrathecal cytarabine (the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment) system chemotherapy must begin with 72 hours of this IT therapy; or\r\n* 600 cGy of chest irradiation, if medically necessary\r\n** Pre-treatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone use during sedation to prevent or treat airway edema; inhalation steroids and topical steroids are not considered pretreatment
Subjects must have ended hormone replacement therapy (HRT) (e.g., conjugated estrogens tablets, USP, [Premarin]), at least 1 month (30 days) prior to receiving the first dose of randomized therapy
Concomitant chemotherapy, radiation therapy\r\n* For patients with hyperleukocytosis with > 50,000 blasts/uL; leukapheresis or hydroxyurea may be used prior to study drug administration for cytoreduction at the discretion of the treating physician; hydroxyurea must be stopped 24 hours prior to initiation of protocol defined therapy
Intrathecal cytotoxic therapy:\r\n* No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone\r\n* At least 14 days must have elapsed since receiving liposomal cytarabine (DepoCyte) by intrathecal injection
Patients must have recovered from the acute effects of prior liver-directed therapy (e.g. RT, radiofrequency ablation [RFA], or transarterial chemoembolization [TACE]), and a minimum of 4 weeks must have passed since the last procedure and protocol therapy
Patients already using topical sirolimus therapy
Therapy with myelosuppressive chemotherapy or biologic therapy < 21 days prior to registration; NOTE: patients who have recovered from cytopenia related to previous treatment and meet criteria of this protocol will be eligible
Prior therapy for the treatment of solitary plasmacytoma is permitted, but > 7 days should have elapsed from the last day of radiation\r\n* NOTE: Prior therapy with clarithromycin, dehydroepiandrosterone (DHEA), anakinra, pamidronate, or zoledronic acid is permitted; any additional agents not listed must be approved by the principal investigator
Prior therapy requirements:\r\n* At least one prior therapy using an agent with the potential for prolonged remission (generally includes interleukin-2, checkpoint-blocking antibodies, or adoptive cell therapy)\r\n* At least 4 weeks from last dose of prior chemotherapy or immunomodulator therapy with resolution of the acute toxicities; for patients coming off molecularly-targeted therapy, at least 2 weeks since last dose and recovery from laboratory and constitutional toxicities; patients must meet entry eligibility criteria\r\n* At least 2 weeks from completion of prior radiation therapy with no residual radiation toxicities\r\n* At least 4 weeks from last dose of prior investigational therapy with recovery to meet baseline eligibility criteria\r\n* Not receiving any current anticancer therapy\r\n* Note: any patient whose tumors carry a B-Raf proto-oncogene, serine/threonine kinase (BRAF) v600 mutation should either be excluded, or may be included after experiencing progression following treatment with BRAF inhibitor regimen or if they consent and agree to forgo Food and Drug Administration (FDA)-approved therapies that increase median survival
Liver-directed therapy (chemoembolization, radioembolization, bland embolization, ablative therapy) within 4 weeks of DEB-TACE
For stage 1 (all patients) and dose expansion (stage 2) endometrial and ovarian cancer cohorts, participants are allowed following unlimited prior therapy; for stage 2 GBM participants, no more than 2 prior relapses are allowed; for these patients, relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy) or a subsequent therapy; the intent therefore is that GBM patients enrolling onto stage 2 had no more than 3 prior therapies (initial and treatment for 2 relapses); if the patient had a surgical resection for relapsed disease and no anti-cancer therapy was instituted for up to 12 weeks, and the patient undergoes another surgical resection, this is considered to constitute 1 relapse\r\n* NOTE: for participants who had prior therapy for a low-grade glioma, the surgical diagnosis of glioblastoma will be considered the first relapse; therefore, these participants may have had more than 3 prior therapies
Patient may have had any prior topical or systemic therapy except for total electron beam irradiation; patients must be a minimum of 2 weeks from topical therapy and 3 weeks from systemic therapies, phototherapy, or local radiation therapy before initiating protocol specific therapy except for HDACI if they are in Arm B; patients are allowed to take weak potency topical corticosteroids if patient has been on a stable dose for more than a month
Prior therapy with other human or humanized monoclonal antibodies, unless HAHA tested\n             and negative
Women diagnosed with osteoporosis may participate in this trial provided they are receiving appropriate therapy or if they have declined therapy
Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy:\r\n* Myelosuppressive chemotherapy:\r\n** Solid tumors: Patients with solid tumors must not have received chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)\r\n** Lymphoma: Patients with lymphoma who relapse during standard maintenance therapy are eligible at time of relapse; for patients with ALCL who relapse while they are receiving cytotoxic therapy, at least 14 days must have elapsed since the completion of cytotoxic therapy; Note: cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of PF-02341066
Prior therapy with LMB-2
Participant treated with any prior systemic therapy for myeloma; treatment by localized radiotherapy is not an exclusion criterion if an interval of at least 7 days between the end of radiotherapy and initiation of protocol therapy is observed; intervals of less than 7 days between radiotherapy and initiation of protocol therapy will be considered on a case by case basis with the lead principal investigator (PI), provided toxicity is not a concern; similarly, the dose of corticosteroids received by the participant as part of initial therapy for myeloma should not exceed the equivalent of 160 mg of dexamethasone over a two-week period before initiation of protocol therapy
Has received locoregional therapy to liver (transcatheter chemoembolization [TACE], transcatheter embolization [TAE], hepatic arterial infusion [HAI], radiation, radioembolization, or ablation) within 4 weeks prior to the first dose of study drug.
Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to frontline therapy frontline therapy with > 3 residual lesions on end-induction MIBG scan.
Prior therapy with any antibody or drug targeting T-cell coregulatory proteins
Prior radio- or toxin-conjugated antibody therapy.
Prior treatment with any adoptive T cell therapy
Prior intra-arterial liver directed therapy, including transcatheter arterial chemoembolization (TACE) or Y-90 microsphere therapy
< 6 months between completion of prior RT and initiation of reirradiation using proton therapy
Prior therapy criteria must be met
Recovery from the effects of previous chemotherapy, with a minimum of 21 days from initiation of last therapy; hydroxyurea or anagrelide may be used to manage elevated cell counts in patients up to the time they begin therapy under this protocol
No prior therapy with IL-15 or IL-15 analog
Hepatic artery embolization or ablation of hepatic metastasis within 3 months of enrollment, prior peptide receptor radionuclide therapy (PRRT) within 4 months or any other cancer therapy within 4 weeks (as long as all toxicities are resolved)
CRLX101 or with any topoisomerase I therapy;
All forms of prior local therapy are allowed as long as patients have either a target lesion, which has not been treated with local therapy and/or the target lesion(s) within the field of the local-regional therapy has shown an increase of ? 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy.
Contraception is recommended for 28 days prior to starting therapy, while participating in this study, during dose interruptions, and for at least 3 days after discontinuation of ibrutinib, 28 days after discontinuation of lenalidomide, and 12 months after discontinuation of rituximab
EXCLUSION FOR TREATMENT: Recent prior therapy: systemic chemotherapy less than 2 weeks prior to infusion or apheresis (6 weeks for clofarabine or nitrosoureas for apheresis) or radiation therapy less than or equal to 3 weeks prior to apheresis; exceptions:\r\n* There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such\r\n* Subjects receiving hydroxyurea or oral maintenance chemotherapy may be enrolled provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment\r\n* Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis or treatment\r\n* Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met; cytopenias deemed to be disease-related and not therapy-related are exempt from this exclusion
Must not have received systemic antineoplastic therapy, including radiotherapy within 7 days of study treatment, with the exception of hydroxyurea or 6-mercaptopurine for the purposes of cytoreduction
Patients must have newly diagnosed active multiple myeloma (MM); except where otherwise indicated below that assessment is required within 14 days, all tests for establishing baseline disease status must be completed within 28 days prior to registration for patients with no prior therapy, or within 28 days prior to initiation of first Induction course for patients with prior therapy
Patients must have been treated with 1-2 courses of therapy as first therapy for AML, commonly described as remission induction; examples include, but are not limited to:\r\n* Anthracycline containing regimens\r\n* Nucleoside analogs as monotherapy or in combination\r\n* Deoxyribonucleic acid (DNA) methyltransferase inhibitors
Limited prior therapy, including systemic glucocorticoids for 1 week or less, 1 dose of vincristine, emergency radiation therapy to the mediastinum, and 1 dose of IT chemotherapy; other circumstances must be cleared by principal investigator (PI) or co-PI
Stable dose of glucocorticoids pre-therapy. If patients are receiving glucocorticoids, the dose should not increase during the 96 hours prior to initiation of therapy.
With the exception of steroid pretreatment (defined below) or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL0932\r\n* Patients receiving prior steroid therapy may be eligible for AALL0932
Patients who have received prior progestin or anti-estrogen therapy during the 3 months before the diagnosis of endometrioid adenocarcinoma of the uterine corpus is established; estrogen therapy alone is allowed
Participant must have received prior treatment with at least one, but no more than three, prior lines of therapy for multiple myeloma. A line of therapy consists of greater than or equal to 1 complete cycle of a single agent, a regimen consisting of combination of several drugs, or a planned sequential therapy of various regimens.
For patients with GIST, patients will have progressed on at least one prior tyrosine kinase inhibitor therapy or be intolerant. If documented to have SDH deficient or PDGFRA-D842V GIST, no prior therapy is required for study entry. Other patients with KIT positive cancers will have progressed on at least one prior therapy.
Any medical contraindications or previous therapy that would preclude treatment with either IRX 2 Regimen 1 or 2 or the surgery, reconstruction or adjuvant therapy required to treat the oral tumor appropriately
Patients must discontinue treatment with H2-blockers (cimetidine, ranitidine, etc.) prior to beginning protocol therapy
Prior systemic antitumour therapy within 28 days before Screening Visit. However, local radiation therapy to any area except for the abdominal/retroperitoneal area including the kidney tumour is allowed
In the absence of rapidly progressing disease, the interval from prior treatment to time of initiation of 5-azacytidine and lirilumab will be at least 2 weeks OR at least 5 half-lives for cytotoxic/noncytotoxic agents; use of one dose of cytarabine (up to 2 g/m^2) is allowed prior to the start of study therapy or hydroxyurea for patients with rapidly proliferative disease is allowed before the start of study therapy and while the patient is on active study treatment, as needed, for clinical benefit and after discussion with the principal investigator (PI); concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted
For phase II, any receipt of cytotoxic, biologic, or immune therapy aimed to treat GIST except for adjuvant imatinib systemic therapy that concluded at least 90 days prior to registration; for phase I, patients are eligible regardless of prior therapy
Patients must have been off therapy for MDS for 2 weeks prior to entering this study, and must have recovered from the toxic effects of that therapy to at least grade 1, unless there is evidence of rapidly progressive disease; use of hydroxyurea (any dose) or cytarabine (ara-C) (up to 1 g/m^2 x 2 doses) for patients with rapidly proliferative disease is allowed before the start of study therapy; these should be stopped for 24 hours prior to the initiation of azacitidine and sorafenib
Prior therapy for NHL
Patients who have received any local therapy (radiotherapy, high-potency corticosteroids, intralesional therapy, laser therapy or surgery) other than biopsy to the target area within 4 weeks prior to first dosing of study agent
Who have received at least two cycles of initial systemic therapy and are within 2 to 12 months of the first dose; mobilization therapy is not considered initial therapy
Prior therapy with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids (any route), and IT cytarabine given at diagnosis is allowed; hydroxyurea and ATRA must be discontinued prior to initiation of protocol therapy; patients who have previously received any other chemotherapy, radiation therapy or any other antileukemic therapy are not eligible for this protocol
Patients that have been previously treated with chemotherapy for hepatoblastoma or other hepatoblastoma-directed therapy (eg, radiation therapy, biologic agents, local therapy [embolization, radiofrequency ablation, laser]) are not eligible
Corticosteroids given with antineoplastic intent within 7 days, or chemotherapy given with antineoplastic intent, targeted therapy, or radiation therapy within 3 weeks, or antibody-based therapy within 4 weeks of the start of study drug
Prior therapy with ruxolitinib
Hormone replacement therapies (estrogens, megestrol acetate) within 14 days prior to day 1 of protocol therapy
If considered for combination therapy:
Hormone replacement therapy of any type, megestrol acetate, or raloxifene within four weeks prior to first study treatment
Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 30 days before first BTCT4465A (Mosunetuzumab) administration
No plans for concomitant antineoplastic therapy (including standard fractionated RT, chemotherapy [chemo], biologic, vaccine therapy or surgery) while on this protocol except at disease progression
Limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy to the mediastinum and one dose of intrathecal chemotherapy; other circumstances must be cleared by principal investigator (PI) or co-PI
Participants with prior therapy, other than therapy including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy to the mediastinum and one dose of intrathecal chemotherapy
Prior systemic fluoropyrimidine therapy (unless given in an adjuvant setting and at least six months earlier); prior topical fluoropyrimidine use is allowed
Prior therapy with Laser-Induced Thermal Therapy (LITT) is allowed but at least 21 days must have elapsed from last LITT, with recovery from all LITT-related toxicities to Grade 1 or less and subsequent histologic documentation of recurrence.
Patients with chronic myeloid leukemia (CML) in chronic phase who have resistance and/or intolerance to frontline TKI therapy; resistance is defined as lack (lack defined as response not achieved or lost by the given dates mentioned hereafter) of CHR (complete hematologic response) within 3 months, lack of major cytogenetic response (MCyR) within 6 months, and lack of CCyR within 12 months of therapy with frontline TKIs; in addition, loss of MCyR, CCyR or MMR at any time during the course of therapy is also considered resistance to therapy; intolerance is defined as persistent or severe toxicity that is unacceptable to the patient
Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational; prior therapy with bisphosphonate is allowed; prior therapy for smoldering myeloma MM may not be an exclusion criterion, discussion with principal investigator must occur before enrolling patients with prior treatments; prior radiation therapy to a solitary plasmacytoma is allowed; patients who received prior therapy due to being incorrectly diagnosed as having overt multiple myeloma may not be excluded after discussion with the overall PI
Completed any systemic therapy (excluding endocrine therapy, which may be ongoing) at least one week prior to planned start of SBRT (two weeks preferred) and must have no plans to initiate systemic therapy for at least one week following end of SBRT (two weeks preferred)
Allowed prior therapies include:\r\n* Surgery (major surgery at least more than four weeks prior to baseline assessment)\r\n* Locoregional therapy such as: chemoembolization, radio-embolization, radiofrequency ablation, radiotherapy as long as there is progressive measurable disease outside the area of locoregional therapy or there is progression in the previously treated areas\r\n* Any number of previous lines of systemic therapy; last treatment before enrollment must have occurred more than 4 weeks for chemotherapy, 6 weeks for antibodies or more than 5 half-lives of prior tyrosine kinase inhibitors (TKIs) or small molecules
No prior therapy with the exception of prior radiation therapy and/or prednisone alone, at the discretion of the investigator based on current diagnosis and clinical condition; this prednisone treatment will not count toward the 6 cycles of treatment given in the study
Subject had previous local therapy (e.g., surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation) within 14 days prior to Day 1, has not recovered from toxicities from prior local therapy or may require major surgical procedure during the course of the study.
Prior history of any viral-based therapy
For patients who have received prior cryotherapy, radiofrequency ablation, radioembolization, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, at least 28 days must have elapsed since that therapy, and lesions that have not been treated with local therapy must be present and measurable.
Ineligible for cisplatin therapy
Failure to recover to grade 1 or baseline from all toxic effects of previous chemotherapy, radiation therapy, biologic therapy, and/or experimental therapy, with the exception of: alopecia, grade =< 2 peripheral neuropathy, grade =< 2 cetuximab-related rash or other skin changes, hypomagnesemia (acceptable values detailed below), hypokalemia (acceptable values detailed below), and the acceptable hematologic values summarized above; a washout period of 2 weeks from prior cetuximab is required; a washout period of 3 weeks from any prior cytotoxic chemotherapy or investigational drug is required
Prior therapy with all choices of active comparator
Intraocular retinoblastoma not previously treated with systemic chemotherapy, radiation therapy, or IA therapy; local retinal therapy such as laser photocoagulation and cryotherapy will be permitted
For unilateral retinoblastoma\r\n* Group A eye that has failed local therapy\r\n* Group B eye that has failed local therapy\r\n* Group C eye that has failed local therapy\r\n* Group D eye\r\n* Group E eye that is not buphthalmic, is not planned for enucleation after first cycle of chemotherapy, and is in a child less than 1 year of age
Patients who have previously been treated with chemotherapy (with the exception of local retinal therapy such as laser photocoagulation and cryotherapy) radiation therapy, or intra-arterial therapy
For patients who have received prior cryotherapy, radiofrequency ablation, Therasphere, ethanol injection, transarterial chemoembolization (TACE) or photodynamic therapy, the following criteria must be met: 28 days have elapsed since that therapy (lesions that have not been treated with local therapy must be present and measurable)
Treatment with any of the following medications or interventions concomitantly or within 28 days of starting ipilimumab: a) systemic corticosteroids; use of inhaled, intranasal, intra-articular and topical steroids is acceptable, as is a short course (i.e. =< 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans; b) external beam radiation therapy or major surgery requiring general anesthetic; c) any systemic therapy for prostate cancer (with the exception of bisphosphonates and receptor activator of nuclear factor kappa [RANK]-ligand inhibitors for bone metastases which are allowed) including chemotherapy, secondary hormonal therapies, (such as megestrol acetate, diethylstilbestrol, ketoconazole, abiraterone, enzalutamide) and non-steroidal anti-androgens (such as bicalutamide, flutamide or nilutamide); d) immune modulators, cytokines or vaccines for the management of cancer or non-cancer-related illnesses; e) any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month before any dose of ipilimumab); f) any other investigational product
If not receiving myelofibrosis therapy, must remain off therapy for at least 2 weeks prior to screen date and through the screening period
Histologically confirmed prostate adenocarcinoma with metastasis either starting or recently started on LHRH analogue therapy; (late induction permitted within 3 months of starting LHRH analogue therapy or antiandrogen); no minimum PSA requirement for patients with measurable disease
Prior therapy with AA
Prior therapy restrictions:
No particle therapy such as but not limited to proton therapy is allowed
Radiopharmaceutical therapy: ?42 days after systemically administered therapy.
Prior treatment with four or more cycles of hypomethylator therapy
The target lesion(s) has not been previously treated with local therapy (such as surgery, radiation therapy, hepatic arterial therapy, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation)
Patients who have received local therapy, such as surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection or cryoablation are eligible if the previously treated lesions have progressed or recurred can be identified as target lesions; local therapy must have been completed at least 4 weeks prior to the baseline scan
Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months from definitive therapy, has a negative imaging study within 4 weeks of irinotecan initiation, and is clinically stable with respect to the tumor at the time of study entry; also, the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to day 1 [D1] of treatment under this study)
Patients may have been treated with locoregional liver directed therapies such as embolization, chemo-embolization including drug-eluting beads doxorubicin chemoembolization (prior non drug eluting beads chemoembolization with doxorubicin is excluded), radiation, radioactive microspheres, etc., provided that they either have a target lesion that has not been subjected to local therapy and/or the target lesion(s) within the field of the local therapy has shown an increase of >= 25% in the size since last treatment; such therapy must be completed at least 4 weeks prior to treatment initiation; patients that have received palliative radiation therapy to the bone need not wait 4 weeks to begin protocol therapy
Prior loco-regional therapy including drug-eluting beads doxorubicin chemoembolization (prior non drug eluting beads chemoembolization with doxorubicin is excluded) is allowed
Prior treatment with 5-azacytidine followed immediately by HiDAC and mitoxantrone as proposed in this study (NOTE: prior therapy with 5-azacytidine or decitabine or HiDAC or mitoxantrone would be allowed-in patients with relapsed/refractory disease- unless the prior therapy was identical to the schema/schedule proposed in this study)
Patients who have had any prior line of systemic therapy including cytotoxic agents or molecularly targeted agents for advanced/unresectable disease; any number of prior regional therapies with transarterial chemoembolization (TACE), brachytherapy with yttrium-90 microsphere, intra-arterial chemotherapy, surgery, or ablative therapy are allowed
Patients who have received prior local therapy, including but not limited to embolization, chemoembolization, radiofrequency ablation, radiation therapy, are eligible provided that measurable disease falls outside the treatment field or within the field but has shown an increase of >= 20% in the size; prior local therapy must be completed at least 4 weeks prior to the baseline scan
Patients with a prior history of liver directed therapy for their HCC (chemoembolization, radioembolization, bland embolization, radiation therapy, radiofrequency ablation, microwave ablation) can participate in the study if the liver-directed therapy was performed more than 4 weeks prior to their first dose of sorafenib and measurable lesions present outside of previously treated field
Hypercalcemia >2.9 mmol/L, unresponsive to standard therapy (e.g., I.V. hydration, diuretics, calcitonin and/or bisphosphate therapy).
Liver function status Child-Pugh Class A. Child Pugh status should be calculated based on clinical findings and laboratory results during the screening period. Local or loco-regional therapy of intrahepatic tumor lesions (e.g. surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >/=4 weeks before first dose of study medication. Note: patients who received sole intrahepatic intraarterial chemotherapy, without lipiodol or embolizing agents are not eligible.
Refractory to prior Bortezomib-containing therapy under the 1.3 mg/m2 dose twice weekly dosing schedule.
ONLY APPLIES TO PATIENTS IN GROUP B (COMBINATION THERAPY)
Prior ADT is allowed if it was an adjunct to definite local therapy, was given for =< 1 year, and was completed at least 12 months before initiating therapy for metastatic disease
Malignancy has failed curative therapy and has no reasonable expectation of cure with available alternative salvage therapy
Prior nitrosurea therapy (including lomustine or Gliadel)
Achieved at least a PR (and not progressed) after ABVD therapy
Patients who have received any systemic corticosteroid therapy within 3 weeks prior to the start of therapy with the exception of physiological replacement doses of cortisone acetate or equivalent
Patients on continuous steroid therapy for at least 72 hours (hrs) (or other continuous immunosuppressives such as azathioprine or cyclosporine A) are excluded on the basis of potential immune suppression; patients must have had 6 weeks of discontinuation of any continuous steroid therapy (taken for at least 72hrs duration) prior to enrollment (except steroids used for allergic reactions or as anti-emetics for systemic chemotherapy which are permitted)
No prior therapy for recurrent ALL is allowed prior to study entry with the exception of intrathecal (IT) chemotherapy; participants who have relapsed while receiving up-front therapy are eligible, but must have recovered from adverse effects from any previously administered agents
Received treatment with chemotherapy, radiation, antibody therapy or other immunotherapy, gene therapy, vaccine therapy, angiogenesis inhibitors, or experimental drugs 14 days prior to first dose of rucaparib and/or ongoing adverse effects from such treatment > NCI CTCAE Grade 1 (Grade 2 non-hematologic toxicity to most recent treatment may be permitted with prior advanced approval from Sponsor).
All patients may have had prior surgery, chemotherapy, and radiation therapy; prior biologic therapy is permitted only for bevacizumab-exposed patients (groups 2 and 4); prior treatment with Gliadel is permitted for all groups
Subjects must have discontinued hormone replacement therapy (HRT) (e.g., conjugated estrogens tablets, United States Pharmacopeia [USP] or premarin), at least 28 days prior to receiving the first dose of randomized therapy
pc-ALCL and MF patients must have progressed or relapsed after treatment with local radiation therapy, phototherapy, topical chemotherapy, or have failed systemic therapy of at least one single agent (e.g., methotrexate or bexarotene or other non-CD30 antibody) or one multi-agent chemotherapy (e.g. CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone); pc-ALCL classified patients are required to have one or more cutaneous tumors that by history have been present for at least 3 months
One prior cytotoxic therapy for the treatment of metastatic disease is allowed. Unlimited regimens using biological agents (vaccines), immunotherapy, or targeted agents is permitted. For example, BRAF inhibitors and ipilimumab are permitted. Patients must have fully recovered from the acute toxicities related to any prior therapy. Prior therapy must be completed ?28 days before the first dose of cyclophosphamide.
Additional Exclusion Criteria for dabrafenib and trametinib combination therapy (Cohort B and C as well as subjects that crossover from monotherapy to combination therapy):
Symptomatic metastatic brain or meningeal tumors unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of FOLFIRI initiation, and is clinically stable with respect to the tumor at the time of study entry; also, the patient must not be undergoing acute steroid therapy or taper (chronic steroid therapy is acceptable provided that the dose is stable for one month prior to and following screening radiographic studies)
Patients with castrate resistant prostate cancer (CRPC) must have no standard options for therapy; prior to registration on the study, patients with CRPC must be at least 3 weeks from their last treatment, such as ketoconazole, abiraterone, low-dose dexamethasone, anti-androgens, or cytotoxic therapy, (excluding ongoing therapy to suppress testosterone, which must also be continued during this trial)
Concurrent therapy with any excluded medications that cannot be safely discontinued prior to initiation of combination therapy; discontinuation prior to enrollment is not required, but discontinuation prior to combination therapy must be possible
Baseline studies must be performed 8 weeks prior to the start of systemic therapy, and must document the extent of disease in the breast; the specifics of this are at physician discretion, but must address clinical signs and symptoms; if pre-therapy scans were not performed, scans performed within the first 4 weeks of systemic therapy, but prior to registration, will be accepted; radiology reports documenting status of disease must be available
Patients must have completed at least 16 weeks of optimal systemic therapy (appropriate to the tumor biological profile and the patient’s age and menopausal status)\r\n* NOTE: The patient will be considered eligible if the last day of the treatment cycle meets the 16 weeks criteria\r\n* If systemic therapy is discontinued for toxicity, there is no distant progression and at least 12 weeks of therapy have been delivered, then the patient remains eligible; if systemic therapy is changed for reasons other than progression of disease (e.g. from chemotherapy to endocrine therapy), the patient remains eligible
Initial therapy must have included total/near-total thyroidectomy and RAI ablation therapy
Have not received anti-cancer therapy for at least 2 weeks prior to study entry, with the exception of low dose ara-C (LDAC) given as subcutaneous injections (no less than 15 days prior), hydroxyurea or anagrelide (no less than 24 hours prior), TKI (no less than 5 days prior), and interferon (no less than 2 weeks prior)
Subjects who received less than four weeks of therapy and were unable to continue therapy due to toxicity will be allowed to participate
The participant is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills, hormone replacement therapy, or megestrol acetate).
Endocrinopathies, unless on stable hormone replacement therapy;
Patients in this trial may receive ovarian estrogen +/- progestin replacement therapy as indicated at the lowest effective dose(s) for control of menopausal symptoms at any time, but not progestins for management of anorexia while on protocol directed therapy.
Any prior therapies such as surgery, chemoembolization, radiofrequency ablation, and alcohol injection are allowed as long as toxicity from such prior therapy is =< grade 1
Prior therapy with Dasatinib
subjects with initial presentation of organ confined recurrent prostate cancer (Stages T1c and T2 only) who have been treated with EBRT (conventional, 3D conformal, or IMRT) or proton therapy, two or more years prior, and currently have biopsy proven local recurrence. Previous radiation therapy must be a documented therapeutic dose of 60 to 81Gy or GyE (gray equivalent) for proton therapy;
No prior therapy for this malignancy except for one dose of intrathecal therapy and the use of hydroxyurea or low-dose cytarabine (100-200 mg/m^2 per day for one week or less) for hyperleukocytosis
Prior therapy with E7389 Halichondrin analog (eribulin)
Prior therapy with modulators of monocyte or TAM function.
Prior therapy:\r\n* There is no waiting period for participants who relapse while receiving therapy if they are free from side effects attributable to such therapy\r\n* Emergent radiation therapy, one dose of intrathecal chemotherapy and up to 7 days of steroids or hydroxyurea are permitted before start of treatment in participants who relapse after completion of frontline therapy; other circumstances must be cleared by principal investigator (PI) or medical designee\r\n* At least 90 days have elapsed since bone marrow transplant and participant is off immune suppression for >= 2 weeks, if applicable
Prior therapy with pemetrexed
Patients may be enrolled on study regardless of the timing of prior Intrathecal therapy; however, they MAY NOT BEGIN TREATMENT ON THIS PROTOCOL UNTIL A MINIMUM OF 7 DAYS HAS ELAPSED SINCE PRIOR INTRATHECAL THERAPY.
Patients should have finished their prior systemic therapy or radiation therapy, at least 3 weeks before cyclophosphamide or granulocyte colony-stimulating factor (G-CSF)/plerixafor mobilization, and should have finished dexamethasone at least 7 days prior to Plerixafor priming; administration of bisphosphonates needs to be completed at least 2 weeks before cyclophosphamide priming; bisphosphonates can be resumed or started after day 30
Naïve to targeted therapy (e.g., BRAFi, MEKi) for advanced disease; prior immune-based therapy in the adjuvant setting or for advanced disease (e.g. interferon alfa, ipilimumab, anti-programmed cell death protein 1 [PD-1], vaccine) will be allowed if > 2 weeks from study entry; prior adjuvant treatment with BRAFi or MEKi will not be allowed
Intrathecal therapy with cytarabine is allowed prior to registration for patient convenience; systemic chemotherapy must begin within 72 hours of the first intrathecal treatment
History of prior therapy with belinostat or AZD1775
Patients who are actively receiving other cytotoxic or antibiologic chemotherapies; for patients with Her-2/neu positive disease, trastuzumab (Herceptin) is NOT ALLOWED on this study, and should be withheld during the 8 weeks of therapy, and can be resumed no sooner than 14 days following completion of protocol therapy
At least 1-4 weeks since prior myelofibrosis therapy, including any erythropoietic or thrombopoietic agent
Receipt of other cancer therapy, immunomodulatory drug therapy or immunosuppressive therapy within 4 weeks prior to 1st dose.
Subject has attempted \best\ medical therapy and has tried and failed at least three documented medically supervised treatments (including, but not limited to physical therapy, acupuncture, etc.) and has failed medication treatment from at least two different classes
Evidence of continuing adverse effect of prior therapy
Meets the requirements for HD IL-2 therapy per Institutional guidelines
Meets the requirements for ipilimumab therapy per Institutional guidelines
The last dose of previous therapy targeting RET kinase must be given at least 4 weeks prior to the first dose of ponatinib
Patients must be clinically suitable for cryoablation therapy
Because patients with immune deficiency are at increased risk of lethal infections when treated with bone marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with bevacizumab, vemurafenib and cobimetinib.
Documented completion of at least 6 cycles of CHOP-based therapy:
Phase I:\r\n* Patients with prior therapy who do not have alternative treatment of higher priority will be eligible\r\nPhase II:\r\n* Patients should not have been previously treated with cytotoxic drugs or drugs included in IPI-biochemotherapy or regional therapy for metastatic malignant melanoma; prior adjuvant interferon is permitted; prior adjuvant Ipilimumab therapy is not permitted; prior therapy with targeted therapy including but not limited to v-raf murine sarcoma viral oncogene homolog B1 (B-RAF), mitogen-activated protein kinases (MAPK)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors etc. is allowed; at least three weeks should have passed since the last dose of prior adjuvant interferon therapy and prior targeted therapies and patient has fully recovered from toxicities of drugs; prior radiation therapy for metastatic melanoma is permitted provided the patient has unirradiated metastatic sites for response evaluation and has fully recovered from its toxicity
Prior cytotoxic therapy for at least 4 weeks before treatment on study; treatment within this 4 week window with corticosteroids is permitted as long as the dose is stable or decreasing; radiotherapy within this 4 week window is permitted as long as it is completed prior to initiating therapy and as long as there is assessable disease for response outside of the radiation field
Stage IIIc or IV histologically proven melanoma (confirmed by Vanderbilt pathologists), that is not curable by standard surgery, radiation therapy, or chemotherapy; no available effective therapy (i.e.; therapy known to be curative); non-biopsied (resected) tumor sites must be measurable for therapy
Willingness to discontinue LHRH analogue therapy and for the duration of the study
Patients receiving full dose anticoagulative therapy
No response to last line of therapy i. PD as best response to most recent therapy regimen ii. SD as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
Prior CAR therapy or other genetically modified T cell therapy
Thiazide (e.g HCTZ, Hydrochoirthiazide) or digoxin therapy (e.g Lanoxicaps, Lanoxin)
Patients who have received antiandrogens or progestational agents as therapy for prostate cancer must discontinue therapy and demonstrate a rising PSA >= 28 days following discontinuation (antiandrogen withdrawal- AAW) (>= 42 days for bicalutamide or nilutamide); patients who receive megestrol acetate as therapy for \hot flashes\ at a dose of =< 40 mg per day may continue this therapy during this trial; the dose of the megestrol acetate should not be changed during protocol treatment; patients undergoing androgen deprivation using LHRH analogues must continue such agents or undergo orchiectomy to maintain castrate levels of testosterone
Prior therapy with belinostat
The study will be limited to patients who are chemotherapy naive; patients may have received prior systemic or liver-directed local therapies for advanced uveal melanoma as long as those treatments do not involve chemotherapy; this includes, but is not limited to: immunotherapy, targeted therapy, transarterial embolization, radiofrequency ablation, or cryoablation; treatment must be completed at least 28 days prior to initiation of study therapy; radiation therapy is also allowed and must be completed at least 28 days prior to initiation of study therapy; lesions treated via radiation or liver-directed therapy may not be used as target lesions unless they demonstrate growth over a minimum of 3 months on subsequent imaging
First-line therapy for AGC, including adenocarcinoma of the GEJ, must have included a\n             combination of at least a platinum- and a fluoropyrimidine-based treatment given\n             concurrently; prior therapy does not need to have included a HER2-directed therapy.
Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period, excluding CNS directed therapy upfront for AML patients and continuing for CNS positive patients as described in Section 4.1. Cyto-reduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start or protocol therapy.
Prior therapy with a conjugated or unconjugated auristatin derivative.
Concurrent chemotherapy, or targeted anti-cancer agents, other than hydroxyurea, low-dose cytarabine, intrathecal therapy and/or low dose maintenance therapy such as vincristine, mercaptopurine, methotrexate or glucocorticoids
Must have completed any systemic therapy at least one week prior to planned start of SBRT (two weeks preferred), and must have no plans to initiate systemic therapy for at least one week following end of SBRT (two weeks preferred)
Prior therapy with radium-223 is allowed
At least 21 days since receipt of chimeric antigen receptor therapy or other modified T cell therapy
Measurable disease using RECIST 1.1 criteria (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapy such as (but not limited to) chemoembolization, embolization, cryoablation, hepatic artery therapy, percutaneous ethanol injection, radiation therapy, radiofrequency ablation or surgery are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ? 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan. Local therapies including chemoembolization do not count as prior systemic therapy.
Radiation therapy, local therapy (except for surgical re-resection), or systemic therapy following first recurrence/progressive disease. Excluded local therapies include stereotactic radiation boost, implantation of carmustine biodegradable wafers (Gliadel), intratumoral or convection-enhanced delivery administered agents, etc.
Hepatic radiation, chemoembolization, and radiofrequency ablation < 4 weeks prior to study day 1.
Last received ONT-10 a maximum of 6 months (unless approved by the medical monitor) prior to receiving the first dose of maintenance or retreatment cohort therapy
Patients can either have had no prior anticancer therapy, multiple lines of either prior chemotherapy/biologic therapy/experimental therapy or, if the patient has anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), prior crizotinib.
NOTE: prior therapy with decitabine, clofarabine, idarubicin (idarubicin hydrochloride), or cytarabine is allowed, unless the prior therapy is identical to the schema/schedule proposed in this study
Local or loco-regional therapy (i.e., surgery, radiation therapy, hepatic arterial embolization, chemoembolization, radiofrequency ablation, percutaneous ethanol injection, or cryoablation) must have been completed >= 4 weeks prior to randomization
No prior systemic therapy, immunotherapy, investigational agent, chemoembolization, radioembolization or radiation therapy within the last 4 weeks.
Prior unanticipated severe reaction to fluoropyrimidine therapy
Progressive disease under last palliative therapy with a history of prior ifosfamide, doxorubicin or taxane therapy for angiosarcoma; up to 4 prior therapies are allowed
Patients may have failed ablative therapy
Patients cannot be receiving HAART (highly active anti-retroviral therapy) therapy
CAR-T infusion or other cellular therapy within 30 days
Prior therapy with Velcade is allowed as long as the patient had at least a PR to prior Velcade therapy, was not removed from Velcade therapy due to toxicity, and will have at least a 6 month Velcade treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month Velcade treatment-free interval).
The participant’s target lesion must be limited to a single biopsy-confirmed tumor; presence of other pulmonary nodules, which may represent synchronous early lung cancer, is allowed as long as no additional therapy is anticipated within 3 months following protocol therapy
Previous cancer therapy for DLBCL other than anthracycline- or anthracenedione based chemoimmunotherapy, monotherapy rituximab prior to first line therapy and/or as a maintenance therapy, or limited field radiotherapy
No prior bortezomib is allowed
b. ?1 prior therapy and one of the following abnormalities: 17p del, p53, 1q amp, 1p del, t(4;14)
Patients must not have received any systemic corticosteroid therapy for 3 weeks prior to the start of therapy with the exception of physiological replacement doses of cortisone acetate or equivalent
Subject must have progressive disease after therapy consisting of one of the Food and Drug Administration (FDA)-approved agents for therapy of metastatic renal cell carcinoma, including but not limited to: sorafenib, sunitinib, or temsirolimus
Patients must have completed standard frontline therapy for newly diagnosed metastatic disease; lung, bone, bone marrow or other metastases are sufficient to qualify as metastatic disease; standard frontline therapy is comprised of a regimen that includes (but is not limited to) multiple cycles of vincristine, adriamycin, ifosfamide, and etoposide; local therapy as dictated by the treating institutions; patients may have received autologous stem cell transplantation or other investigational agents as part of their primary therapy
At the time of enrollment, at least 3 weeks and no more than 8 weeks should have elapsed since the last cycle of cytotoxic therapy or since the last dose of radiation therapy, and patients should have recovered from toxic side effects of previous therapy to a grade 1 or less, with the exception of the following:\r\n* Hematological toxicity: recovery to required levels\r\n* Low electrolyte levels (such individuals should receive appropriate supplementation)\r\n* For patients on anticoagulant therapy or with pre-existing coagulation abnormalities, PT, PTT must return to baseline\r\n* Liver function tests must resolve to required values\r\n* Grade 3 hypoalbuminemia is permitted\r\n* Alopecia is permitted\r\n* Sterility is permitted
No prior radiation therapy to the liver including Y90-, I131-based loco-regional therapy. Prior loco-regional therapy based on other technology for HCC, if any, must have been completed at least 4 weeks prior to baseline imaging
Patients must have recovered from the acute effects of prior liver-directed therapy (e.g., radiation therapy [RT], radiofrequency ablation [RFA], MWA or transarterial chemoembolization [TACE]) and a minimum of 4 weeks must have passed since the last procedure and protocol therapy
Corticosteroids should not be used as anti-emetic therapy; corticosteroid therapy is not permissible except for the following indications: \r\n* As treatment or prophylaxis for anaphylactic reactions\r\n* As a treatment for symptoms of cytarabine (Ara-C) syndrome (including fever, rash, or conjunctivitis)\r\n* Physiologic replacement stress-dosing as indicated for suspected or confirmed adrenal insufficiency
For transplant-ineligible patients, salvage therapy just prior to MDV9300 treatment must have resulted in a PR or stable disease;
Have received between 1-2 prior cytotoxic treatments, not to include belinostat, RDHAP, or autologous or allogeneic stem cell transplant; radiation which was pre-planned to occur at the conclusion of systemic cytotoxic therapy will not be considered a separate prior therapy; radiation administered for potential recurrent or relapsed disease will be considered a separate prior therapy
Liver-directed therapy (hepatic artery chemoembolization [HACE], hepatic artery embolization [HAE], selective internal radiation therapy [SIRT]) or peptide receptor radionuclide therapy (PRRT) =< 56 days of first dose of study drug
Has the ability to stop anticoagulant and anti-platelet therapy for seven days prior to and seven days post procedure,
Oral or transdermal estrogen therapy is not allowed
Not be receiving treatment with another antipsychotic agent such as risperidone, quetiapine, clozapine, phenothiazine or butyrophenone for =< 30 days prior to registration or planned during protocol therapy (patients may have received prochloperazine and other phenothiazines as prior anti-emetic therapy)
A self-reported current practice of yoga or any other mind-body therapy, including but not limited to meditation or hypnosis therapy in the past 30 days prior to study enrollment
Prior hepatic arterial therapy or hepatic radiation therapy; prior surgical resection or ablation of liver metastases is acceptable; patients must be at least one month beyond prior radiotherapy or surgery, and 6 months beyond chemotherapy and have recovered from all therapy-associated toxicities
No therapy restrictions
Patients’ post-operative treatment must have included at least 80% of standard radiation and concomitant temozolomide; patients may not have received any other prior chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, tumor infiltrating lymphocytes [TIL], lymphokine-activated killer [LAK] or gene therapy), or hormonal therapy for their brain tumor; prior Gliadel wafers are allowed; glucocorticoid therapy is allowed
Patients being treated with antibacterial agents, other than any of the following:\r\n* Cotrimoxazole or other agents including dapsone, atovaquone, and pentamidine administered for Pneumocystitis jiroveci (PCP) prophylaxis\r\n* Topical antibiotics\r\n* Central venous catheter antibiotic lock therapy\r\n* Note: prophylactic antifungal therapy is NOT an exclusion criterion
Patients on hormone-replacement therapy (HRT) =< 4 weeks prior to registration; this includes the use of vaginal estrogen therapy
Participants must be receiving systemic glucocorticoid therapy for cGVHD; all immunosuppressive therapy may include but not be limited to tacrolimus, sirolimus, CellCept, cyclosporine, and systemic corticosteroid must be at stable doses for 28 days prior to the first cell infusion
The following patient-related situations are allowed: prior surgery, concurrent treatment, homecare, residing in assisted living or a skilled nursing facility, and hospitalization during radiation therapy
Pilot: Patients having been treated for stage III ovarian cancer, and received either intraperitoneal therapy/intravenous therapy or Intravenous therapy only
Abnormal global longitudinal strain (< 19%, or a % decrease of >= 11% from baseline) prior to initiation of planned anti-HER2 therapy
Patients must not have received prior regional therapy such as ablation, embolization, or radiation therapy for at least 2 weeks prior to the first dose of study treatment; patients who receive such therapy should have evidence of radiologic progression at this site or other progressing measurable disease
Have a major contraindication to methylphenidate (MP) (e.g., allergy/hypersensitivity to study medications or their constituents), light therapy (e.g., currently receiving ultraviolet A [UVA]/ultraviolet B [UVB] therapy), cognitive behavioral therapy (e.g., schizophrenia), or conditions making adherence difficult as determined by the attending physician
Patients must not have received or implemented any other medical therapy, alternative therapy, or physical therapy for the treatment of joint pain/stiffness within 28 days prior to registration; therapeutic massage is allowed
Prior therapy with romidepsin
No limitations exist for type or amount of prior therapy
Patients who have never utilized art therapy at Maroone Cancer Center
Clinically suitable for cryoablation therapy
Need for intravenous therapy more frequently than every 3 weeks or inability to time intravenous therapy treatment before and after the study
Any prior therapy with radium-223, samarium, or strontium
Receipt of intravenous immunoglobulin therapy (IVIG) < 27 days prior to calendar day of vaccination
Timing from prior therapy: Stratum 1: Enrollment no later than 60 days after completion of upfront therapy, (last dose of cis-retinoic acid) with a maximum of 6 cycles of cis-retinoic acid maintenance therapy. Stratum 2, 3 and 4: Enrollment no later than 60 days from last dose of the most recent therapy.
Receipt of intravenous immunoglobulin therapy (IVIG) < 27 days prior to vaccination
No cancer therapy in the prior 3 months (excluding chemoprevention agents)
No future cancer therapy planned
Receipt of locoregional therapy (LRT) with verification of complete response at least 30 days following treatment
Receiving maintenance therapy with mesalamine for at least 3 months
Prior endoscopic therapy for BE
Prior therapy with anthracyclines
No prior systemic therapy EXCEPT patients may be consented and enrolled if they have already started mFOLFIRINOX for up to four cycles
Patients must be willing to complete a bilateral mammogram at baseline with repeat exam after 12 cycles of protocol therapy; patients who have had a mammogram within 1 month prior to registration to protocol therapy will not need to repeat the exam
Hormone therapy, including vaginal estrogen creams
If not receiving antiretroviral therapy:                \r\n* CD4-cell count >= 350 cells/mm³ within 90 days prior to study entry\r\n* No plans to start antiretroviral therapy prior to week 28
Individuals can have a prior history of cancer; these individuals must be in stable remission and at least 6 months out from the completion of surgery/radiation therapy/chemotherapy; individual cases can be reviewed with the institutional principal investigator
Individuals can have a prior history of cancer; these individuals must be in stable remission and at least 6 months out from the completion of surgery/ radiation therapy/ chemotherapy; individual cases can be reviewed with the institutional principal investigator
Has a plan for cystoscopic surveillance (adjuvant intravesical therapy allowed)
There will be no therapy restrictions
Neoadjuvant chemotherapy or radiation therapy prior to prostatectomy including focal ablation techniques (high-intensity focused ultrasound ablation [HiFu])
Any surgical therapy in the area of the oral cavity or pharynx within the last 2 weeks
Neoadjuvant chemotherapy or radiation therapy prior to prostatectomy\r\n* Including focal ablation techniques (high-intensity focused ultrasound therapy [HiFu])
Patients should not have begun therapy, or, needed research imaging can be performed within 2-5 days of starting therapy
Any types and amounts of prior therapy will be allowed for this study
Surgical resection, chemotherapy, radiation therapy, or biologic therapy since last Octreoscan + CT; continuation of the same dose of Sandostatin-LAR or subcutaneous Sandostatin is allowed
Patients are deemed suitable for therapy with ADT and EBRT
Prior MAGE-A3/A6-targeting therapy
Any history of radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy (except paliative care outside of the chest).
Residual side effects to previous therapy over specific grade prior to initiation of therapy
Any types and amounts of prior therapy will be allowed for this study
Prior therapy is not a consideration for protocol entry and prior therapy is not an exclusion criteria
Being considered for salvage therapy
Documented normal LVEF for at least 6 months after the initiation of recommended HF therapy
Received any systemic therapy within 21 days prior to planned B-WARM therapy\r\n* Patients may be enrolled on study but at least 21 days should elapse prior to date of B-WARM therapy
Prior therapy with crizotinib.
Prior CAR therapy or other genetically modified T cell therapy
Prior treatment with any therapy targeting mutant IDH1 (including BAY1436032)
Prior therapy with CD123- or IL-3R-directed immunotherapies, including monospecific and bsAbs, immunoconjugates, or chimeric antigen receptor- modified T-cell therapy
STEP I: Patients must have received no more than one cycle (4 weeks or less) of prior chemotherapy and no more than 160 mg of prior dexamethasone (or equivalent dose of prednisone) for treatment of symptomatic myeloma; they should not have been exposed to lenalidomide, bortezomib or carfilzomib for treatment of symptomatic myeloma; prior radiation therapy to symptomatic lesions is allowed provided there are no residual toxicity related to radiation and blood counts that meet the study requirements
Prior breast or thoracic radiation therapy (RT) for any condition
Patients cannot have had prior chemotherapy or biologic therapy for small cell lung cancer for front line treatment; patients receiving prior whole brain radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1
Patients may have received prior radiation therapy, but must have measurable disease outside the radiation port; at least 14 days must have elapsed since completion of prior radiation therapy; patients must have recovered from all associated toxicities at the time of registration
No treatment with radiation therapy =< 28 days before study registration
Participants may not have had radiation to the lung fields within four weeks (28 days) of starting treatment; for patients receiving palliative radiation to thoracic vertebrae, ribs or other sites where the radiation field includes the lungs, radiation must be completed at least two weeks before starting treatment; for all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting to treatment; at least six months (180 days) must have elapsed from radiation given with curative intent
At least one site of metastatic disease or primary disease must be determined by radiation oncologist to be treatable with radiation.
Patients planning to receive EPP must also be evaluated for appropriateness of radiation therapy (RT) by a radiation oncologist within 14 days prior to step 2 registration
Prior radiation therapy (RT) (any site) with concurrent lapatinib defined as 1 or more days on which the patient received both radiation therapy and lapatinib on the same day
Prior treatment\r\n* Cohort A: No prior therapy received other than surgery\r\n* Cohort B: Prior radiation therapy required (any type of prior radiation is allowed)\r\n** For patients treated with external beam radiation therapy, interstitial brachytherapy or radiosurgery, an interval of >= 3 months must have elapsed from completion of radiation therapy to registration\r\n** Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity attributed to radiation with exception of alopecia, fatigue\r\n* For patients enrolling on Cohort A or Cohort B:\r\n** For patients treated with surgery, an interval of >= 21 days must have elapsed prior to registration\r\n** No prior treatment with BRAF or MEK inhibitors\r\n** Steroid dosing stable for at least 4 days prior to registration
Prior radiation therapy within 28 days of starting the study treatment
Patients must have histologic proof of malignancy suitable for thoracic radiation therapy
Patients who received radiation therapy > 5 years ago for malignancies other than breast cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry
Prior radiation therapy or radionuclide therapy for the treatment of metastasis
Receipt of radiation therapy within 3 weeks of scheduled C1D1 dosing, unless the radiation comprised a limited field to non-visceral structures (e.g., limb bone metastasis).
Meningioma that have resulted from prior radiation therapy are allowed
Patients must have histologically confirmed glioblastoma that is progressive or recurrent following radiation therapy and temozolomide according to the Response Assessment in Neuro-Oncology (RANO) criteria with:\r\n* New contrast-enhancing lesion outside of radiation field on decreasing, stable, or increasing doses of corticosteroids\r\n* Increase by >= 25% in the sum of the products of perpendicular diameters between the postradiotherapy scan with the smallest tumor measurement and a scan at least 12 weeks from completion of radiation therapy (RT) + temozolomide (TMZ), on stable or increasing doses of corticosteroids\r\n** Note: clinical deterioration not attributable to concurrent medication or comorbid conditions is sufficient to declare progression on current treatment but not for entry onto a clinical trial for recurrence
Patients with a history of prior cranial radiation are ineligible
Prior radiation therapy to the chest [Period 2]
Prior radiation therapy:\r\n* Patients may have received prior radiation therapy in either the metastatic or early-stage setting\r\n* Radiation therapy must be completed at least 14 days prior to registration
Previous radiation in the current area of disease requiring radiation
Prior radiation therapy (RT) of greater dose intensity than 100 Gy2 based on a biological effective dose (BED) calculation
Must have failed previous radiation treatment or combined treatment with temozolomide and radiation.
If progression of disease occurs within three months of conformal radiation, it must be outside of the radiation field or proven by biopsy/resection.
Patient has completed chemo-radiation within the last three months, unless new contrast enhancement is outside of radiation field, or there is tissue proven recurrence or progression.
Prior therapy:\r\n* There is no limit on the number of prior surgeries, radiation therapy, radiosurgery treatments or systemically administered therapeutic agents\r\n* Patients may have been treated with standard external beam radiation or radiosurgery in any combination, however, an interval of >= 12 weeks (84 days) must have elapsed from the completion of the radiation therapy to start of study therapy unless there is histopathologic confirmation of recurrent tumor or there is new enhancing tumor outside the radiation field (beyond the high dose region or the 80% isodose line)\r\n** In addition, there must be subsequent evidence of tumor progression after completion of radiation therapy\r\n* An interval of >= 28 days and full recovery (no ongoing safety issues) from surgical resection (>= 7 days from stereotactic biopsy)\r\n* For prior systemic agents, participants must be at least 4 weeks (or 5 half-lives, whichever is shorter) from other prior cytotoxic chemotherapy (6 weeks from nitrosoureas) or biologic therapies
Radiation therapy
Participants must have developed progressive disease after receiving prior radiation therapy and must have an interval of at least 12 weeks from the completion of any radiation therapy to study entry (unless progressive tumor growth is outside the radiation field or there is histopathological confirmation of recurrent tumor)
Radiation therapy within 7 days before the first dose of cabozantinib; subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible
Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol; consolidative radiation therapy (RT) after completion of planned course and/or concurrent intrathecal chemotherapy for central nervous system (CNS) disease prophylaxis is permissible
Prior radiation therapy is acceptable but there cannot be major overlap of the previously irradiated tissues with the new radiation treatment volumes anticipated to be delivered for the purposes of this protocol, in such a way that curative intent with radiation cannot be met; furthermore, the total dose from all radiation delivered and expected to be delivered should not exceed the suggested dose constraints given for normal structures
Patients with widespread superficial multifocal BCC who are considered unresectable due to breadth of involvement and do not have a single definable area of disease amenable to radiation therapy targeting\r\n* Note: if an area including one or more lesions is definable for radiation therapy targeting, the patient may be eligible for treatment on study using the designated target lesion(s) identified by the investigator
Prior treatment with radiation to the thoracic region
Radiation therapy within 14 days prior to first dose
Prior radiation therapy encompassing >25% of skeleton
Prior liver radiation therapy (RT) is an exclusion unless subject participation is approved by the principal investigator (PI)
Deemed a suitable candidate for radiation therapy by the treating radiation oncologist as documented in a standard pretreatment visit per standard practice at each participating institution
Patients must have least 1 non-central nervous system (CNS) based lesion; palliative radiation must be potentially indicated for at least one lesion, and this lesion must be a reasonable candidate for radiation to a dose of 8 Gy in 3-5 fractions as deemed by a treating radiation oncologist in terms of the ability to meet standardly accepted radiation dose constraints; any unirradiated lesions must not require urgent palliative local treatment
Prior radiation therapy:\r\n* Patients must be at least 3 months from prior radiation therapy\r\n* Re-irradiation of the same field is not allowed
Received more than one course of radiation therapy or more than a total dose of 75 Gy.
Patients may have received prior radiation therapy in either the metastatic or early-stage setting; radiation therapy must be completed at least 14 days prior to study participation and patients should have recovered from adverse effects of radiation to grade =< 1
Prior adjuvant or salvage radiation or not a candidate for radiation based upon clinical assessment of disease characteristics and patient co-morbidities.
Not recovered from radiation and chemotherapy-induced AEs
Prior radiation therapy allowed
Prior radiation therapy within 30 days prior to study Cycle 1 Day 1 and/or persistence of radiation-related adverse effects
No prior radiation therapy to the region for separate cancer
Treatment includes localized radiation therapy with or without chemotherapy
Not pregnant per radiation oncology standard procedures
Prior radiation therapy to the larynx area or involved neck.
?14 days for chemotherapy, targeted small molecule therapy, or radiation therapy. Subjects must also not have had radiation pneumonitis as a result of treatment, and cannot participate in the study if they are on chronic corticosteroids for radiation pneumonitis. A 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval. Note: Bisphosphonates and denosumab are permitted medications.
Recent chemotherapy or radiation therapy (within 14 days before first dose of lenzilumab)
Patients may not have received prior radiation therapy to a site of recurrence which would require overlap of appreciable radiation dose
Radiation w/in 4 wks, or limited field radiation w/in 2 wks, prior to study drug, or w/unresolved Grade ?1 side effects
For patients following definitive radiation therapy or cryotherapy: a rise in PSA of > 2 ng/mL above the nadir (per Radiation Therapy Oncology Group [RTOG]-American Society of Therapeutic Radiation Oncology [ASTRO] consensus criteria)
Patients with a history of prior cranial radiation are ineligible
Prior radiation is permitted; however, at least 2 weeks must have elapsed since the completion of prior radiation therapy and patients must have recovered from all radiation-associated toxicities to no greater than grade 1 at the time of registration
Prior radiation dose of at least 50 gray (Gy)
Prior radiation to the breast or thorax.
Prior radiation therapy and/or chemotherapy, including cyclophosphamide, are permitted
Has a known contraindication to radiation therapy, including inherited syndromes associated with hypersensitivity to ionizing radiation such as ataxia-telangiectasia and Nijmegen breakage syndrome.
Prior radiation allowed
Patients should have discontinued all previous intensive therapy, chemotherapy or radiotherapy for 2 weeks prior to commencing therapy on this study\r\n* NOTE: low dose chemotherapy or maintenance chemotherapy given within 7 days of planned study enrollment is permitted; these include hydroxyurea, 6-meraptopurine, oral methotrexate, vincristine, oral etoposide, and tyrosine kinase inhibitors (TKIs); FLT-3 inhibitors can also be given up to 3 days before conditioning regimen\r\n* All patients with prior radiation treatment to the lung, liver, and kidney will be excluded; for other scenarios of prior radiation treatment, up to 2000 centigray (cGY) at 2 gray (Gy) per day will be allowed; inclusion of patients with previous radiation exposure will be determined based on the radiation oncologist medical doctor (MD) evaluation and judgment
Prior history of radiation to the mediastinum
History of prior whole brain radiotherapy (WBRT) other than prophylactic cranial radiation. Prophylactic cranial radiation with a maximum dose of 25 Gy delivered as 10 fractions is allowed. WBRT in excess of 25 Gy (anything over 25 Gy) is not allowed
Prior thoracic radiation is allowable if degree of overlap with the esophageal radiotherapy treatment is deemed to be safe by the treating radiation oncologist
Concurrent therapy considered investigational\r\n* NOTE: patients must not be planning to receive any radiation therapy (except localized radiation for palliative care that must be completed prior to starting cycle 1, day 1)
Concomitant use of any other anti-cancer therapy or radiation therapy. Palliative radiation therapy to non-target lesions is permitted
Previous radiation therapy with anything other than standard radiation therapy (i.e., focally directed radiation) administered as first line therapy.
Participants must not have had prior radiation therapy (defined as > 10% of prior prescription dose) to the area planning to be treated with SBRT
Agreeable to consider radiation therapy (RT) for the urothelial cancer: patients have to be evaluated by a radiation oncologist and deemed to be candidates for RT
Previous radiation therapy to lesion to be resected
Radiation
Prior radiation therapy to the abdomen that would overlap with treatment field
Prior radiation to affected area
Prior radiation treatment to the upper abdomen
Patients who have received maximally allowed doses (given in 2 Gy fractionations, or equivalent) of previous radiation therapy to various organs; patients who previously have received a higher than allowed dose of radiation to a small lung, liver and brain volume, will be evaluated by the radiation oncologist to determine if the patient is eligible for study
Recovery to baseline from acute toxicity related to prior therapy, including surgery and radiation; (28 days removed from last systemic therapy, 14 days removed from last radiation therapy)
Eligible for treatment with radiation therapy
Received definitive chemotherapy and radiotherapy prior to recurrence/progression or who are unable to receive radiation therapy due to genetic disorders that put them at significant risk for radiation-induced secondary malignancies (i.e. Gorlin’s syndrome or NF1 mutation)
Patients who have had radiation to the lung fields within four weeks of starting treatment; for patients receiving palliative radiation to thoracic vertebrae, ribs or other sites where the radiation field includes the lungs, radiation must be completed at least two weeks before starting treatment; for all palliative radiation to all other sites, at least 7 days must have elapsed prior to starting to treatment; at least six months must have elapsed from radiation given with curative intent
Radiation therapy within 14 days of starting study treatment
Participants must otherwise be indicated for proton radiation therapy
Prior radiation to the same site deemed to be too high of level of radiation for retreatment
Lactation and a radiation field which would include the breast or nipple or deemed to place the mother or child at elevated risk of radiation exposure (evaluated by MRP, ARM, WR, WW)
Candidate for radiotherapy (as determined by treatment physician); these patients can have symptomatic disease and/or asymptomatic disease; a minimum of one site of radiation is required to any osseous and/or any extra-osseous disease; radiation to any bony parts of the head and neck, skull, spine, ribs, and/or extremities are allowed; radiation to any bony part for documented lytic disease is allowed; radiation to any soft tissue plasmacytoma (including osseous and extra-osseous plasmacytoma) is allowed; the only exclusion criteria for radiation, is central nervous system (CNS) metastases
Prior radiation therapy of any type within 7 days of first dose of study medication
Prior history of scalp radiation or intolerance to standard course of radiation treatment
Patients with a history of prior thoracic radiation > 30 gray (Gy)
Participants who have had prior liver directed radiation treatment, including selective internal radiation (SIRspheres or Theraspheres)
Has had prior radiation therapy (defined as > 10% of prior prescription dose) to the area planning to be treated with SBRT
Has had prior radiation therapy within the past 3 months where the high dose area of the prior radiation would overlap with the high dose area of the intended radiation based on the judgement of the treatment oncologist.
Has had prior radiation therapy to the potential radiation target such that additional radiation therapy is considered unsafe by the treating radiation oncologist
Patient who underwent chemotherapy, radiation therapy within 15 days before the screening period
Has at least one extracranial tumor safely treatable with radical-dose radiation therapy
Prior radiation therapy within the last 14 days
Patients with prior chemotherapy or radiation therapy for their diagnosis of esophageal or gastric cancer. Patients with prior radiation therapy to same site for another diagnosis of cancer. Note: Patients may receive palliative radiation to their symptomatic sites of metastases but not definitive local therapy to esophageal or gastric primary prior to randomization. All patients may be enrolled on protocol then start systemic therapy; if they do not have evidence of disease progression at re-staging following initial therapy, they may be randomized
Patients with prior radiation therapy to the same bronchopulmonary segment
Patients may have received prior radiation therapy in either the metastatic or early-stage setting; radiation therapy must be completed at least 14 days prior to study registration
No prior mediastinal or thoracic radiation
Treatment plan for bladder must include at least 4 weeks of daily radiation treatment (most patients will receive chemotherapy concurrent with radiation, but this is not required for trial enrollment)
Ongoing radiation therapy, chemotherapy, or hormonal therapy. Point radiation to a site of bone pain will be allowed.
History of symptomatic CTCAEv4 grade >= 3 pneumonitis following the initial course of definitive radiation therapy
Patients who received radiation therapy > 5 years ago for malignancies other than pancreatic cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry
Patients must be planning to undergo standard radiation/chemotherapy
Prior radiation therapy will be allowed if active measurable disease was not previously treated with radiation therapy
Radiation therapy within 14 days of enrollment
Prior salvage or adjuvant radiation therapy is allowed but not mandated; radiation therapy must have been completed for at least 6 months
If during treatment planning, the target dose of radiation cannot be achieved within published limits of dose limiting organs in the opinion of the treating radiation oncologist, the patient will be ruled ineligible and treated off protocol
PRE-SCREENING: If prior radiation, measurable lesion outside radiation portal
An interval of >= 12 weeks from the end of prior radiation therapy is required unless there is either:\r\n* Histopathologic confirmation of recurrent tumor, or\r\n* New enhancement on MRI outside of the radiation treatment field
Radiation therapy (XRT) >= 6 months from involved field radiation to index plexiform neurofibroma(s); >= 6 weeks must have elapsed if patient has received radiation to areas outside index plexiform neurofibroma(s)
Craniotomy site must be adequately healed and free of drainage or cellulitis, and the underlying cranioplasty must appear intact at the time of radiation; radiation must start within 6 weeks of surgery
Concurrent therapy considered to be investigational; NOTE: patients must not be planning to receive any radiation therapy (except localized radiation for palliative care that must be completed prior to starting cycle 1, day 1)
Prior radiation therapy to the prostate
Prior history of HNSCC receiving radiation or chemo-radiation.
Subjects must have a least one site of disease that is accessible to radiation and multiple biopsies; subjects may have disease that is encompassed within the radiation field or may have known disease both inside and outside of the radiation field
Prior radiation resulting in overlapping radiation fields
cSCC that is curable via radiation or surgery; palliative radiation is allowed as long as measurable disease outside radiation field is present for study
Patients must be assessed to be a suitable candidate for hemithoracic radiation therapy per the treating radiation oncologist; if the patient undergoes pleurectomy/decortication, they must initiate hemithoracic radiation therapy within 4 months of the surgery date; patients that do not meet the dose constraints outlined below will be removed from the study prior to radiation therapy
Patients must be assessed to be a suitable candidate for radiation therapy by the treating radiation oncologist; patients that do not meet the dose constraints outlined below will be removed from the study prior to radiation therapy
Patients in which hemithoracic radiation therapy is planned
Prior radiation therapy allowed as long as completed in the following times prior to initiation of trial treatment:\r\n* Definitive curative intent radiation >= 3 weeks prior to trial treatment\r\n* Palliative body radiation >= 1 week prior to trial treatment\r\n* Stereotactic brain radiation >= 1 week prior to trial treatment\r\n* Whole brain radiation >= 2 weeks prior to trial treatment
Prior chest wall radiation
Radiation oncologist recommends radiation treatment to the supraclavicular and infraclavicular fossa (i.e. RNI)
History of urological surgery or procedures predisposing to genitourinary (GU) complications after radiation, i.e., anastomoses, stricture repair, transurethral resection, etc. (will be determined by radiation oncologist)
At least 6 weeks must have elapsed prior to enrollment since the patient received any prior radiation therapy, and the target cutaneous neurofibromas have to be in areas outside of a prior radiation field
Radiation therapy is not permitted within 14 days of registration
Prior radiation therapy within the field of the target lesion that in the opinion of the treating radiation oncologist would preclude further palliative radiation to a dose of 30 gray (Gy)
Patient is considered low-risk and would not have received adjuvant radiation therapy (RT) outside of this study
Prior history of fractionated radiation therapy
History of prior radiation therapy to the upper abdomen
Subjects who have had radiation therapy within 1 week prior to first dose of drug
Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder\r\n* NOTE: No radiation therapy within 28 days prior to being registered for protocol therapy; laboratory values must be obtained within 14 days prior to being registered for protocol therapy
Plan for chemotherapy or targeted therapies during whole brain radiation or within 1 week of completing radiation therapy
Prior radiation therapy is allowed
Patients who have received prior radiation therapy must have recovered from toxicity of the prior radiation therapy prior to registration, and must have disease evaluable for response outside of the radiation fields or have evidence of post-radiation progression of previously irradiated sites of disease
Planned stereotactic body radiation therapy (SBRT) for the pulmonary metastases
Radiation oncology consultation at enrolling site to confirm that disease can be encompassed in a radiotherapy field =< 56 days prior to registration\r\n* NOTE: Radiotherapy quality assurance rapid review must be performed before the first fraction of radiation therapy (RT) is administered; if RT constraints cannot be met, the patient will be removed from the protocol prior to treatment
Active cancer that requires therapy in the form of chemotherapy or radiation
Progressive disease via Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) on prior study or standard of care therapy utilizing an immunotherapy agent OR a clinical status that requires salvage radiation treatment (e.g.: palliative radiation therapy [RT]) at the discretion of treating physician and/or principal investigator (PI)
We will allow prior radiation to other sites, with no washout period, prior to study entry as long as the high dose regions of the prior and proposed radiation fields do not overlap
Has had prior radiation therapy within the past 3 months where the high dose area of the prior radiation would overlap with the high dose area of the intended radiation based on the judgment of the treating radiation oncologist
Prior standard radiation therapy to a dose ranging from 50 to 60 Gy at 1.8 to 2 Gy per fraction
We will allow prior radiation to other sites, with no washout period, prior to study entry as long as the high dose regions of the prior and proposed radiation fields do not overlap; in patients where the prior high dose area would overlap with the high dose area of the intended radiation, a 4 month washout period will be required; the safety of such treatment will be at discretion of the treating radiation oncologist
Prior central nervous system (CNS) radiation is allowed as long as cumulative radiation doses do not exceed tolerance of critical structures as judged by the treating radiation oncologist
History of prior mediastinal radiation
Prior radiation therapy within the last 14 days
Prior radiation is allowed prior to study start (1st dose of study medication) if at least 21 days must have elapsed since prior large-field radiation therapy and recovered from all treatment related toxicity; at least 3 months must have passed since radio-immunotherapy
Has had prior radiation therapy (defined as > 10% of prior prescription dose) to the area planning to be treated with SBRT
Evidence of potential delivery of\r\n* Greater than 30 Gy absorbed dose of radiation to the lungs during a single 90Y resin microsphere administration? or\r\n* Cumulative delivery of radiation to the lungs > 50 Gy over multiple treatments
Previous radiation therapy to the lungs and/or to the upper abdomen
Previous therapeutic radiation therapy (RT) that exceeds critical structure tolerance doses as determined by a radiation oncologist
Patients may have had radiation therapy, but must have progressive disease after radiation therapy if the lesions to be treated are within the radiation field. Radiation treatment must be completed ? 4 weeks prior to Cycle 1 Day 1.
Prior radiation therapy to the abdomen and/or lower thorax
Patients receiving intraoperative radiation therapy (IORT)
Patients are eligible to participate within 6 months of completion of therapy for their breast cancer; this includes prior radiation therapy if needed
Prior radiotherapy to the thorax such that composite radiation would significantly overdose critical structures, either per estimation of the treating radiation oncologist or defined by failure to meet normal tissue tolerance constraints
Patients may have received radiation therapy to painful bone metastases or areas of impending bone fracture as long as radiation therapy is completed >= 2 weeks prior to day 1 of cycle 1 of treatment; patients who have received prior radiotherapy must have recovered from toxicity (=< grade 2) induced by this treatment; baseline radiologic scans must be obtained after completion of radiation
Use of systemic chemotherapy and/or radiation therapy =< 14 days prior to first registration; palliative radiation therapy is permitted for irradiating small areas of painful bony metastases that cannot be managed adequately using systemic or local analgesics
Use of systemic chemotherapy and/or radiation therapy after first registration; palliative radiation therapy is permitted for irradiating small areas of painful bony metastases that cannot be managed adequately using systemic or local analgesics
The patient cannot have had prior radiation therapy to the thorax or upper abdomen
Has had prior radiation therapy to all available thoracic and liver lesions such that additional radiation therapy is unsafe by the opinion of the treating radiation oncologist
Radiation therapy in the last 14 days
Patients should have histologically confirmed chordoma by the Laboratory of Pathology, National Cancer Institute (NCI), which is advanced and not considered resectable; if the original tissue cannot be retrieved, diagnostic documentation at an outside institution will be acceptable; they must have planned radiation therapy to at least one targeted lesion with evidence of growth prior to enrollment; the tentative radiation plan at enrollment must be in compliance with the required radiation doses; this can be given in standard or hypofractionated dosing with any technique deemed most appropriate by the treating radiation oncologist if other requirements are met
Patients must have fully recovered from prior surgery before enrollment; prior radiation therapy is allowed provided the radiation field can safely be irradiated within the guidelines in the opinion of the treating radiation oncologist
No limit to number prior anti-cancer regimens, including chemotherapy, biologic agents, immunotherapy, vaccines, monoclonal antibodies or radiation therapy; patients who have received prior radiation therapy for this tumor are eligible; there should be at least 2 years time since the completion of radiation therapy
Radiation therapy (RT): patients must have had their last fraction of cranial or craniospinal radiation >= 24 months prior to study entry
Less than 2 years since completion of radiation therapy
Prior radiation therapy is not an exclusion however, patient must have documented progression at the radiation site
Prior abdominal radiation; any prior radiation must be approved by the radiation oncology principal investigator (PI)
No prior radiation therapy to the liver
History of previous radiation therapy which would result in overlapping radiation fields
Prior breast or thoracic radiation therapy (RT) for any condition
If post-transplant consolidation radiation therapy is given, the patient must be at least 14 days between last radiation treatment and 1st dose of rituximab
Patients with a history of treatment with radiation therapy are excluded
Interval from start of initial radiation therapy to enrollment > 9 months
Patients will be ineligible if chemotherapy was completed >= 1 year from the planned start date of radiation therapy or if the patient is referred for radiation therapy after a relapse following a regimen with chemotherapy alone
Patients may have received previous radiation therapy, but it must have been completed at least 21 days prior to enrollment and the patient should have recovered from all associated toxicities. Measurable or non-measurable disease must be present outside the previous radiation field or a new lesion inside the radiation port must be present.
Able to cooperate with radiation safety restrictions during therapy period
Radiation therapy within 14 days of screening
No prior radiation to the mediastinal structures
Prior therapeutic radiation to target tissues for protocol radiation
Patients should be at least four weeks from the last day of therapeutic radiation or cytotoxic chemotherapy or from antibody therapy, or at least five half-lives from non-cytotoxic targeted or biologic therapy; patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available
Prior thoracic radiation allowable only if there is minimal to no overlap with the treatment area estimated at the time of consultation
Patients must be at least 12 months from completion of radiation therapy (to be consistent with the \rechallenge\ group from Perry et al. Journal of Clinical Oncology [JCO] 2010 where the median time from completion of adjuvant radiation therapy to the time of progression was 19.69 months)
Patients must not have had any radiation therapy or chemotherapy for medulloblastoma prior to study enrollment
Prior thoracic radiation therapy preventing hemithoracic pleural IMRT
Prior radiation therapy to the upper abdomen or liver
Prior radiation to the index breast
Tumor types – tumor type/location:\r\n* Stratum A: newly diagnosed diffuse intrinsic pontine gliomas OR any biopsy proven high-grade glioma involving the brainstem; patients may not have received chemotherapy during or after radiation; patients must be registered within 4-12 weeks of completing radiation\r\n* Stratum B: newly diagnosed, non-brainstem high-grade glioma; patients may not have received chemotherapy during or after radiation; patients must be registered within 4-12 weeks of completing radiation\r\n* Stratum C: unresectable low-grade gliomas that have received at least two chemotherapy/biologic regimens; patients may not have received radiation to the index lesion within 1 year of enrollment \r\n* Stratum D: non-brainstem high-grade gliomas that have recurred following treatment\r\n* Stratum E: newly diagnosed high-grade gliomas or brain stem gliomas who received chemotherapy during radiation therapy; patients may not have received chemotherapy after radiation therapy was completed; patients must be registered within 4-12 weeks of completing radiation  \r\n* Stratum F: newly diagnosed high-grade gliomas with metastatic disease within the central nervous system (CNS) requiring craniospinal radiation therapy; patients may or may not have received chemotherapy during radiation, but cannot have received chemotherapy after radiation therapy was completed; patients must be registered within 4-12 weeks of completing radiation
Able to cooperate with radiation safety restrictions during therapy period
Documentation that either: 1) the patient’s medical insurance company has certified that they will pay for the cost of radiation therapy treatments, or 2) a letter from the patient indicating that they explicitly understand the costs of radiation therapy and that the sponsor (Principal Investigator) of this study will not be held responsible for these costs
Unacceptable radiation therapy quality assurance parameters
For patients treated with external beam boost, prior chemotherapy if administered less than 3 weeks from start of radiation therapy or chemotherapy < 3 weeks after finishing radiation therapy; for patients treated with brachytherapy intracavitary device, chemotherapy prior to start of radiation therapy (RT)
Patients with tylectomies so extensive that the cosmetic result is low or poor prior to radiation
Prior radiation therapy with 400c gray (Gy) or more of TBI
Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs on either: 1) first TheraSphere administration; or 2) cumulative delivery of radiation to the lungs over multiple treatments
Evidence of potential delivery of greater than 16.5 mCi (30 Gy absorbed dose) of radiation to the lungs on either: 1) first TheraSphere administration; or 2) cumulative delivery of radiation to the lungs over multiple treatments
Prior radiation therapy that prevents further TBI
If subject has not undergone radiation therapy, then subject must have undergone prior consultation with a radiation oncologist (who is not an investigator on this study); if the subject has undergone radiation therapy, then at least 14 days must have elapsed since completion of radiation
Prior radiation to the area of measurable or active tumor.
Subjects may have had prior focal or systemic radiation or chemotherapy; at least 14 days must have elapsed since radiation treatment and 28 days since prior chemotherapy
Tooth extraction prior to radiation
Previous inclusion in a research protocol involving nuclear medicine, positron emission tomography (PET) or radiological investigations with significant radiation burden (a significant radiation burden being defined as 10 mSv in addition to natural background radiation, in the previous 3 years). Exclusion Criteria for Group 1 Has any of the following:
Prior radiation therapy within 30 days prior to enrollment.
The patient should be off chemotherapy, biologic therapy and radiation for 28 days.
Active central nervous system (CNS) metastasis, which has not been treated with radiation therapy. If treated with radiation therapy, treatment must end before 14 days prior to starting study treatment.
Prior exposure to chemotherapy or radiation for the disease to be treated on this trial not allowed
Therapeutic radiation within 6 weeks of cycle 1 day 1; exceptions are palliative radiation and/or stereotactic radiation to non-target lesions
A maximum of one prior radiotherapy regimen, curative or palliative, to the head and neck is allowed; if the radiation is combined with chemotherapy and/or cetuximab, a minimum of 4 months must elapse between the end of radiotherapy and registration; if the radiation is given alone, a minimum of 8 weeks must elapse between the end of radiotherapy and registration; a minimum of 3 weeks must elapse between prior radiation to other areas and registration; treatment areas should be healed with no sequelae from radiation therapy (RT) that would predispose to fistula formation
Any radiation therapy within 21 days prior to day 1 of protocol therapy
All sites of disease must be targetable with intensity-modulated radiation therapy (IMRT) with acceptable morbidity and without exceeding normal tissue dose constraints as assessed by a radiation oncologist
Prior radiation or systemic therapy for the diagnosis of liposarcoma
Concurrent malignancy or malignancy within 3 years prior to starting study drug, with the exception of malignancies that have completed therapy and are considered by their physician to be at less than 30% risk of relapse; prior systemic therapy is allowed with the exception of prior eribulin; prior radiation therapy is allowed with the exception of any abdominal, pelvic or retroperitoneal radiation > 10 Gy
Recommendation for combined chemotherapy and radiation therapeutic treatment
The subject must have completed prior radiation therapy at least 28 days prior to registration for protocol therapy\r\n* NOTES: Subjects may have received prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy; chemotherapy used for radiation sensitization is allowed; chemotherapy used for radiation sensitization will not count as second chemotherapy regimen
Clinically safe to delay radiation for at least 2 weeks
An interval of at least 12 weeks from the completion of radiation therapy to start of study drug unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field (defined as the region outside the high-dose region or 80% isodose line) or there is unequivocal histologic confirmation of tumor progression
Prior treatment \r\n* Prior medical therapy is allowed but not required\r\n* No limit on number of prior therapies\r\n* No chemotherapy, other investigational agents within 28 days of study treatment\r\n* No other concurrent investigational agents or other meningioma-directed therapy (chemotherapy, radiation) while on study\r\n* For patients treated with external beam radiation, interstitial brachytherapy or radiosurgery, an interval > 24 weeks must have elapsed from completion of radiation therapy to registration\r\n* Steroid dosing stable for at least 4 days \r\n* Recovered to Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or less toxicity from other agents with exception of alopecia and fatigue\r\n* No craniotomy within 28 days of registration
Extensive prior therapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation as per the assessment of the radiation oncologist
Radiation therapy in the last 14 days; palliative radiation to a localized area without residual toxicity requires a washout of greater than 7 days
Any prior chemotherapy or radiation therapy for the current diagnosis
Has received re-radiation to recurrent disease (other than standard frontline adjuvant radiation therapy)
Patients may have received prior radiation therapy for treatment of endometrial cancer; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, intravaginal brachytherapy and/or palliative radiation therapy; all radiation therapy must be completed at least 4 weeks prior to registration
No prior intracranial radiation
No previous chemotherapy or radiation therapy
Prior therapy requirements:\r\n* Prior radiation, chemotherapy or biologics NOT allowed
Prior breast or thoracic radiation therapy (RT) for any condition
Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
Prior history of radiation to the chest
Prior radiation therapy (RT) > 20 Gray (Gy) to a critical organ within 1 year of enrollment
Patients may have received prior radiation presuming > 4 weeks since last dose and measurable disease outside the radiation field
Patients cannot have had prior chemotherapy or biologic therapy for SCLC or large cell neuroendocrine NSCLC, or small cell carcinoma of unknown primary or extrapulmonary origin; patients receiving prior radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
Patients receiving prior radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
PHASE II: Patients cannot have had prior chemotherapy or biologic therapy for small cell lung cancer; patients receiving prior radiation cannot register within 7 days after completion of radiation, and must have resolved adverse events attributed to radiation to =< grade 1; no previous irradiation to the only site of measurable or evaluable disease, unless that site had subsequent evidence of progression
Patients that have received prior radiation to the lung, excluding prior mediastinal radiation
No prior chemotherapy or radiation therapy for HGG or DIPG is permitted; prior chemotherapy or radiation therapy for treatment of other malignancies is permitted
Prior radiation therapy must have been completed > 2 weeks prior to randomization and the patient must be recovered from any acute toxicities associated with radiation therapy; previously irradiated lesions must not be the sole site of disease
Prior chemotherapy, and/or radiation therapy is allowed if it has been at least 3 years or longer since those therapies were given from the time of registration, with the exception of previous pelvic radiation which is NOT allowed under any circumstances
Patients who received prior radiation therapy (RT) for treatment of germ cell tumor are eligible for this study as long as there is evidence of progressive disease determined by tumor markers or other sites of metastases outside of the radiated site; radiation must be completed prior to starting chemotherapy with the exception of brain metastases where chemotherapy and radiation can be given concurrently; toxicity from radiation must have recovered to grade 1 or less prior to initiating chemotherapy
Patients may not have had radiation within 28 days prior to first dose
Patients may have received prior radiation therapy, including after the surgical resection; all adverse events associated with prior surgery and radiation therapy must have resolved to =< grade 1 prior to registration
PRIOR/CONCURRENT THERAPY CRITERIA: Patients may have had prior radiation therapy as long as it has not affected greater than 25% of the bone marrow and at least one measurable lesion is outside the area of prior radiation; at least 7 days must have elapsed since last radiation treatment; patients must have recovered from any adverse events from prior radiation therapy to =< CTCAE grade 1
Planned liver directed therapy or radiation therapy
Patients may have received prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy
Tumor mass(es) accessible for intratumoral injection and are being considered for local radiation therapy and at least one additional site of disease outside the radiation field for assessment of distal (abscopal) response
Prior radiation is allowed if the index lesion(s) remains outside of the treatment field or has progressed since prior treatment. Radiation therapy must have been completed at least 4 weeks prior to the baseline scan
Prior treatment:\r\n* Must have completed standard radiotherapy and concomitant TMZ therapy as defined and determined by the study oncologist\r\n* Besides concomitant TMZ with radiation, no other therapy (neo-adjuvant or adjuvant) can be given prior to study registration, including chemotherapy (also including Gliadel/carmustine [BCNU] wafers), biologics, immunotherapy, radiation therapy; the only exception is the Optune device (NovoTTF-100A), which may be started any time after end of radiation therapy up through the initiation of Cycle 1; intent to use Optune must be declared at registration for stratification\r\n* No prior allogeneic bone marrow transplant or double umbilical cord blood transplantation
The subject has had palliative radiation therapy to bone metastases within 14 days prior to the Day 1 visit (side effects from radiation must be resolved).
Prior radiation therapy within 28 days of starting the study treatment, except radiation therapy for bone metastases or radiosurgery is permitted up to 14 days of starting treatment
Prior radiation therapy within 30 days prior to enrollment.
Radiation therapy requirements
Timing of Radiation - radiation therapy must begin no later than 30 days after the date of radiographic diagnosis or definitive surgery, whichever is the later date.
Received a radiosensitizer or any additional adjuvant therapy during radiation therapy.
Previous definitive chemotherapy (chemo)-radiation is permitted for early stage tumors (cisplatin-based chemo-radiation is permitted but only if tumor progression/relapse occurs after 6 months from treatment completion)
The patient must have completed chemoradiation (all cohorts) within standards of care established by prior Radiation Therapy Oncology Group (RTOG)/Network Radiotherapy Group (NRG) Oncology studies as follows:\r\n* Radiation therapy\r\n** Modality: either 3-dimensional (3D) or intensity-modulated radiation therapy (IMRT), or proton therapy is allowed\r\n** Time to initiation: radiotherapy must be initiated within or equal to 42 days after surgery\r\n** Target volumes: target volume definition will be based upon postoperative-enhanced MRI; preoperative imaging should be used for correlation and improved identification, as necessary\r\n** Dose guidelines: the initial target volume will be treated to 46 Gray (Gy) in 23 fractions; after 46 Gy, the cone-down or boost volume will be treated to a total of 60 Gy, with seven additional fractions of 2 Gy each (14 Gy boost dose)\r\n* Temozolomide during concomitant radiation therapy\r\n** Temozolomide must have been administered continuously from day 1 of radiotherapy to the last day of radiation (+/- 3 days to take into consideration holidays) at a daily oral dose of 75 mg/m^2 for a maximum of 49 days (except missed doses due to toxicity)
Patient must have consulted with a radiation oncologist who is planning radiation; radiation should be completed within a 2-week window from start to finish
Patients may receive local palliative radiation therapy immediately before or during the treatment if the radiation therapy is not delivered to the sole target lesions
History of urological surgery or procedures predisposing to genitourinary (GU) complications after radiation (will be determined by radiation oncologist)
Prior radiation therapy (RT) that precludes the delivery of SBRT
Prior single modality radiation therapy is allowed
Prior radiation therapy (RT) > 20 gray (Gy) to a critical organ within 1 year of enrollment
History of urological surgery or procedures predisposing to genitourinary (GU) complications after radiation, i.e., anastomoses, stricture repair, etc. (will be determined by radiation oncologist)
No prior therapy for MCL, except: < 2 weeks of steroid therapy for symptom control or local radiation therapy for symptom control if there is measurable disease outside the radiation portal; patients may be on chronic steroids for non-malignant disease if on a stable dose equivalent to =< 20 mg prednisone per day
Patient must be considered able to tolerate systemic chemotherapy combined with pelvic radiation therapy, and a radical cystectomy (if necessary) by the joint agreement of the participating urologist, radiation oncologist, and medical oncologist
Prior radiation therapy of any kind is allowed.
In patients who have received prior radiation, at least 4 weeks should have elapsed since the completion of radiation therapy involving the whole pelvis or over 50% of the spine; if vaginal brachytherapy is planned with chemotherapy, it should be done before or after completion of chemotherapy treatment
Prior radiation or surgery is allowed, but should be finished at least 2 weeks prior to study enrollment; if a participant has prior radiation therapy, at least one measurable lesion outside of the radiation field should be available for the evaluation of response to chemotherapy
History of prior chest radiation therapy
Radiation therapy:
An interval of at least 12 weeks from the completion of radiation therapy to start of study drug unless there is a new area of enhancement consistent with recurrent tumor outside the radiation field or there is unequivocal histologic confirmation of tumor progression
Prior radiation is allowed
Patients with a history of prior radiation therapy to the thorax
No radiation within 4 weeks of mobilization attempt
Tumor progression or recurrence within 6 months of last dose of platinum therapy in the adjuvant (ie with radiation after surgery), primary (ie, with radiation), recurrent, or metastatic setting
Progressive disease if treated with chemotherapy, radiotherapy, surgery or immuno-therapy. If prior radiation was given, the measurable disease should be outside the radiation port.
Radiation therapy (XRT): >= 6 months from involved field radiation to index plexiform neurofibroma(s); >= 6 weeks must have elapsed if subject has received radiation to areas outside index plexiform neurofibroma(s); subjects who have received radiation to the orbit at any time are excluded
No prior chemotherapy, radiation, or biotherapy
COHORT A: Current or prior radiation therapy to the prostate; prior radiation to a metastatic site (e.g., palliative radiation) is allowed
Prior radiation to a target lesion is permitted only if there has been clear progression of the lesion since radiation was completed; if patient receives single dose radiation for palliation or radiation to non-target lesion, they may immediately proceed to registration without waiting; acute adverse events from radiation must have resolved to =< Common Terminology Criteria for Adverse Events (CTCAE) v 3.0 grade 1
Patients who received radiation therapy > 5 years ago for malignancies other than pancreatic cancer and whose radiation therapy field is not overlapping with the 20% isodose line of current radiation field are eligible, provided that radiation therapy was completed > 5 years ago and that there is no evidence of the second malignancy at the time of study entry
Primary treatment with radiation therapy
Previous radiotherapy to thorax (prior breast radiation therapy [RT] is permitted).
Prior radiation therapy precluding SBRT
No prior chemotherapy or radiation therapy; emergent radiotherapy to preserve vital organ function is permitted; participants who receive emergent radiation will not be eligible for window therapy
Study-specific exclusions:\r\n* History of prior radiation to the pelvis\r\n* History of uncontrolled inflammatory bowel disease\r\n* Unable to comply with radiation therapy procedures
Patients may have received prior radiation therapy; all adverse events associated with prior radiation therapy must have resolved to =< grade 1 prior to registration
Prior radiation therapy to the liver
No prior radiation above the clavicles
Patients who have undergone partial breast radiation (duration =< 7 days) prior to registration are eligible; partial breast radiation must be completed prior to 2 weeks before starting protocol therapy; patients who have undergone whole breast radiation are not eligible
Prior treatment with embolization (including bland embolization, chemoembolization, and selective internal radiation therapy) or ablative therapies is allowed if measurable disease remains outside of the treated area or there is documented disease progression in a treated site; there is no limit on the prior number of procedures; prior liver-directed or other ablative treatment must be completed at least 8 weeks prior to registration; index lesions for the purpose of RECIST 1.1 measurements will not be selected from within the radiation therapy treatment field; however, if there is evidence of disease progression within the radiation treatment field, measurement of the progressing lesions will be documented
Radiation therapy within the 14 days prior to Day 1.
Prior radiation therapy of any kind is allowed
Recipients of prior abdominal radiation therapy (focal splenic radiation is acceptable)
Endometrial cancer patients must be at least 3 months post-active chemotherapy and/or maintenance therapy treatment but not greater than 5 years post-active chemotherapy and/or maintenance therapy treatment; they must be at least 4 weeks post-radiation therapy (external beam radiation therapy [EBRT] or intravaginal radiation therapy [IVRT]) but not greater than 5 years post-radiation therapy
Prior history of standard dose CNS radiation of 60 Gy in 30 fractions or 59.4 Gy in 1.8 Gy fractions, or equivalent or lower doses\r\n* Patients who have received prior treatment with non-standard radiation therapy (RT) dose and fractionation, interstitial brachytherapy, stereotactic radiosurgery, etc. are eligible as long as the criterion is met or approved by a principal investigator
Currently receiving cancer therapy (chemotherapy, radiotherapy, immunotherapy, or biologic therapy) NOTE: palliative radiation therapy is permitted for non-target lesions that are either new or present at baseline provided total dose does not exceed 30 grays (Gy); however, radiation skin injury has been reported with concurrent use of dabrafenib and radiation
STEP 2 ENROLLMENT AND RANDOMIZATION: concurrent chemoradiation is permitted as consolidative therapy; the following concurrent therapies are permitted: tyrosine kinase inhibitors (i.e. erlotinib) - can be delivered with both hypofractionated (>= 3 Gray [Gy] per fraction) and standard fractionated radiation therapy (< 3 Gy per fraction); platinum-based chemotherapy - standard fractionated radiation therapy (< 3 Gy per fraction)
Patient must not have had radiation therapy within 14 days of enrollment
Prior radiation to the esophagus
Prior mediastinal radiation
Patients must be at least 28 days from last radiation therapy dose, surgery, or tumor embolization prior to the first dose of pazopanib/PCI-24781
Intraventricular chemotherapy or radiation therapy within 4 days of starting treatment
Current or prior radiation therapy to the prostate
Prior history of radiation or chemotherapy for MCL
Patients must have no prior chemotherapy or radiation therapy for lymphoma
Previous radiation treatment that includes the liver in the main radiation field
Previous therapeutic radiation therapy (XRT) to the liver as part of involved-field radiation
Information on previous radiation treatment, including total dose and fractionation must be available; additional information including radiation fields and dose-volume-histogram or isodose lines is preferable
Prior radiation of greater than 60 Gy to > 20% of brainstem
Patients who experience surgical complications which prevent radiation from starting for 3 months or more
History of urological surgery or procedures predisposing to genitourinary (GU) complications after radiation (will be determined by radiation oncologist)
Prior history of fractionated radiation therapy
DIPG patients only (enrollment plan 2 and 3)\r\n* Diagnosis of diffuse intrinsic pontine glioma (DIPG) by magnetic resonance imaging (MRI); biopsy will not be required for study enrollment\r\n* Completion of standard radiation therapy (not to exceed 5580 centigray [cGy]) with a post radiation therapy (RT) MRI that shows no disease progression when compared with pre-RT MRI; all patients must be treated with intensity modulated radiation therapy (IMRT) or an equivalent conformal technique; the clinical target volume will be defined as the gross tumor volume (full extent of tumor visible on MRI) plus 1 cm margin; patients from an outside institution who are referred after the start of radiation therapy may complete initial radiation therapy at their home institution as long as dosage guidelines are met and the total dose does not exceed 5580 cGy at the time of study registration\r\n* Able to begin vaccination 4 weeks (+/- 1 week) of completion of standard radiation therapy\r\n* Age 18 months and older
Prior radiation therapy to the abdominal area which would overlap with the proposed area of treatment
Patients with no prior treatment with intracranial radiation therapy (ICR) may be included unless ICR is emergently indicated (in consultation with a local therapist, i.e. neurosurgeon or radiation oncologist)
Patients must be judged to be candidates for complete resection with free margins followed by radiation therapy (if radiation therapy is indicated)
If radiation was previously received, the measurable disease must be outside the previous radiation field, unless this area has demonstrated evidence of radiographic growth
No prior radiation therapy or chemotherapy
Patients may receive concurrent radiation therapy to painful sites of bony disease or areas of impending fracture as long as the radiation therapy is initiated prior to study entry and sites of measurable and non-measurable disease outside the radiation therapy port are available to follow; patients who have received prior radiation therapy must have recovered from toxicity of the prior radiation therapy
Radiation within 14 days of starting study treatment
A history of radiation pneumonitis in the radiation field (fibrosis) is permitted provided that symptoms have resolved
Prior radiation therapy in excess of 20 Gy to the site of the current diagnosis of sarcoma. No overlap with prior radiation fields in excess of 20 Gy is allowed.
Patients should be at least four weeks from the last day of therapeutic radiation or cytotoxic chemotherapy or from antibody therapy, or at least five half-lives from non-cytotoxic targeted or biologic therapy; patients may have received palliative radiation immediately before (or during) treatment provided radiation is not to the only target lesion available
No prior radiation to the thorax that would overlap with the current treatment field, prior radiation to other areas is allowed
Patients with prior radiation therapy will be excluded
Patients will be ineligible if chemotherapy was completed >= 1 year from the planned start date of radiation therapy or if the patient is referred for radiation therapy after a relapse following a regimen with chemotherapy alone
History of radiation or chemotherapy
No previous radiation treatment to the head (unless the ports for that radiation entirely excluded the brain) for any condition
Patients who have already received > 45 gray (Gy) to the craniospinal radiation or > 72 Gy focal brain radiation
Radiation/chemotherapy within 21 days
Never received radiation therapy at index level(s) (following consult with radiation oncologist re: conventional treatment options) OR Received radiation therapy without adequate relief from metastatic bone pain as determined by the patient and treating physician, their treating physician would not prescribe additional radiation treatments, or refuse additional radiation therapy,
Ongoing radiation therapy, radiation therapy administered within 30 days of enrollment.
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
No prior radiation therapy to the chest, breast or supraclavicular fossa that would limit radiation delivery to the full prescription dose
Localized radiation therapy within the last 14 days
Patients who have previously received radiation therapy to the chest or abdomen such that there would be overlap between the previous and current radiation field
Prior radiotherapy to the thorax such that composite radiation would significantly over-dose critical structures, either per estimation of the treating radiation oncologist or defined by failure to meet normal tissue tolerance constraints
Carcinoma requiring systemic chemotherapy or radiation therapy
The time interval between CNS radiation, whole brain radiation, spinal cord radiation, or radiosurgery, and initiation of protocol specified chemotherapy must be at least 1 week
Previous radiation allowed provided that 2 weeks has passed since radiation and/or the patient has recovered from the side effects
Ongoing radiation therapy, radiation therapy administered within 30 days of enrollment
Prior radiation therapy to the prostate
Patients must be clinically suitable for radiation therapy
Patients who have undergone prior ablation treatment or radiation therapy of the index tumor
Received maximal radiation therapy
Prior breast radiation therapy
Prior radiation treatment to the HN region
Prior Therapy: \r\n* Prior Chemotherapy: Patients who have had a prior chemotherapy regimen for advanced or metastatic disease are excluded\r\n* Prior Radiation Therapy: Patients may have received prior radiation therapy for treatment of endometrial carcinoma; prior radiation therapy may have included pelvic radiation therapy, extended field pelvic/para-aortic radiation therapy, and/or intravaginal brachytherapy, alone or with chemotherapy as a radiation sensitizer; all radiation therapy must be completed at least 4 weeks prior to the first date of study therapy, the prior radiation field, radiation dose, number of fractions and prior radiation start and stop dates must be provided at registration
Has had prior chemotherapy or radiation.
Patients must have received prior radiation treatment to the chest; records of prior radiation treatment must be available
Patients must have received prior chest radiation at least 3 months prior to enrollment in this trial; radiation treatment to other body sites not overlapping with current radiation fields are allowed within the 3 months period (example, brain radiation is allowed)
Patients who received radiation to the chest within the past 3 months (in a region that overlaps with current radiation fields)
Receipt of radiation therapy within 3 weeks of scheduled dosing day 1, unless the radiation comprised a limited field to non-visceral structures (eg, a limb bone metastasis).
Prior radiation to the chest wall or mediastinum if the radiation field involves the heart
Prior chemotherapy or radiation (within 30 days prior to the procedure or the duration of the subject's enrollment);
After radiation therapy (e.g., external beam radiation, brachytherapy, or salvage/adjuvant radiation therapy after surgery), two post radiation PSA measurements level of nadir plus 2.0 ng/mL at least one week apart.;
At least 28 days since chemotherapy or radiation
Patient must have consulted with a radiation oncologist who is planning radiation; their radiation oncologist should have documented plans to administer a dose of at least 30 Gy in 5 or fewer fractions
Prior radiation therapy to the upper abdomen or liver at the discretion of the treating radiation oncologist could impair delivery of the prescribed radiation treatment
Radiation is integral to the primary treatment of glioma; all participants on this study must have had prior radiation to the brain; radiation must have been completed 14 days prior to first study treatment
Previous therapies: prior radiation therapies, immunotherapies, and investigational therapies are allowed as follows:\r\n* Radiation: prior radiation therapy is allowed with the following conditions:\r\n** Patients who have received minimal radiation therapy (=< 5% of their total marrow volume) must have completed it >= 2 weeks prior to the initiation of study treatment\r\n** Patients who have received radiation therapy that constituted > 5% but < 50% of their total marrow volume must have completed it >= 4 weeks prior to the initiation of study treatment\r\n** Patients who have received prior radiation to 50% or more of their total marrow volume will be excluded\r\n** Patients may be biopsied while undergoing radiation therapy as long as biopsy site is not in the radiation portal; however, they still have to wait the required amount of time from radiation to treatment even though the tumor board may have already occurred and a treatment plan assigned\r\n* Other therapies: prior investigational or targeted therapies and immunotherapies may be allowed following discussion with the principal investigator; if the principal investigator (PI) deems the prior treatment acceptable, patients must not have received these therapies for 28 days or five half-lives of the drug (whichever is lesser) prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies; prior therapy with mitogen-activated protein kinase (MEK) inhibitors will not be allowed
Received treatment with any systemic chemotherapy, experimental agent, or radiation therapy (with the exception of palliative localized radiation therapy) following completion of treatment on the ONT-10-001 study
Patients receiving palliative radiation to skeletal metastases may be registered as early as 1 week after completion of radiation therapy provided toxicities are =< CTC grade I at the time of registration
Ongoing radiation therapy and/or radiation therapy administered within 28 days of enrollment or ongoing radiotherapy-related toxicities.
History of radiation therapy to the chest
Patients must have histologic proof of a malignancy suitable for radiation therapy
Prior radiation therapy to the lungs
Patients must have had at least 1 prior systemic chemotherapy (not just steroids or local radiation); last chemotherapy or radiation must be at least 4 weeks prior to enrollment on this study; patients who decline other potentially curative therapy may be eligible; prior radiation therapy must not have been to more than 25% of the bone marrow; whole pelvic radiation is considered to be over 25%
Evaluation by a thoracic surgeon and a radiation oncologist within 2 months of registration
Patients may have had radiation therapy, but must have progressive disease after radiation therapy if the lesions to be treated are within the radiation field
Unlimited prior treatment with radiation or chemoradiotherapy
Patient who have received chemotherapy, immunomodulatory drugs (e.g., lenalidomide, thalidomide or pomalidomide), immunotherapy, radiation therapy, or any investigational drug(s) within 14 days before enrollment or who have not recovered from the side effects of the therapy to at least grade 1; localized radiation therapy to a single site within 7 days is acceptable
If GBM, greater than or equal to 12 weeks from radiotherapy, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field.
Prior radiation or surgery is allowed, but should be finished at least 2 weeks prior to study enrollment; if a participant has prior radiation therapy, at least one measurable lesion outside of the radiation field should be available for the evaluation of response to chemotherapy
Patients must not receive concomitant radiation with chemotherapy if they do not have any measurable lesions outside of the radiation field
Prior radiation therapy within the last 4 weeks; prior radiation therapy to indicator lesion (unless objective disease recurrence or progression within the radiation portal has been documented since completion of radiation)
Prior radiation for NHL, except for a single course of locally delimited radiation therapy with a radiation field not exceeding 2 adjacent lymph node regions
Must be planning to undergo standard radiation therapy.
Radiation therapy involving chest (axilla excluded), mediastinum, or abdomen (i.e., small or large bowel) completed within 10 weeks of transplant admission; radiation therapy shortly before the start of the preparative regimen is allowed
Prior radiation therapy for TCC
Has completed pre-RE angiogram up to 3 weeks prior to Y-90 therapy\r\n* Lung shunt fraction =< 20% and anatomy amenable to intra-arterial radiation delivery\r\n* Extrahepatic vessels deemed at risk for radiation injury were successfully embolized
Prior radiation of cholangiocarcinoma or gallbladder carcinoma; NOTE: adjuvant radiation therapy is allowed if completed > 6 months prior to the start of registration
Prior dose of radiation overlapping the treatment field determined by a study Radiation Oncologist to represent unacceptable risk for additional radiation to be targeted to the field
Radiation therapy within prior 6 months
Prior radiation therapy for lymphoma
Sarcomas where radiation is not planned preoperatively
Patients with prior radiation therapy to the treatment site
Men who have undergone radiation therapy alone will be excluded
those for whom their treating physician would not prescribe radiation or additional radiation treatments
patients who refuse additional radiation therapy.
Patients must be clinically stable and off treatment (e.g. radiation or chemotherapy) for >= 6 months
Participants may have received prior radiation therapy in either the metastatic or early-stage setting; radiation therapy must be completed at least =< 14 days prior to initiation of study therapy
Prior radiation is permitted, provided it does not limit the ability to deliver per-protocol radiation in the opinion of the treating radiation oncologist
Receipt of radiation to the abdomen for any reason during the planned 10-day treatment time
Have had cancer treatment that included a surgical procedure, radiation therapy (RT), and/or chemotherapy (CTX)
History of prior cranial radiation therapy
With prostatic cancer at least 2 months after the end of their radiation therapy
No history of radiation therapy to the tumor and/or surgical area prior to the current treatment being studied
History of radiation therapy to the tumor and/or surgical area prior to the current treatment being studied
Plan for post operative radiation therapy
Radiation plan consisting of regional nodal radiation
Patients who require immobilization with a thermoplastic mask for radiation treatment
Patients receiving radiation therapy with chemo?sensitization
Chemotherapy or radiation therapy within the last 60 days
The involved bone(s) is/are orthopedically stable and not in need of stabilization via either definitive radiation therapy (RT), surgical intervention, or both
Radiation therapy naive
Diagnosis of breast cancer, received chemotherapy, and scheduled to receive 4 to 6 weeks of radiation therapy (radiation protocol of 40 Gy+)
Previous radiation therapy to the area to be treated with radiation therapy
Radiation protocol of 3-dimensional conformal radiation therapy (3D-CRT)/intensity-modulated radiation therapy (IMRT)/image-guided radiation therapy (IGRT)/stereotactic/proton/electron/accelerated fractionation/hyperfractionation/hypofractionation
Patients must have CD4 =< 300 cells/mm^3 in the last week (7 days) of standard radiation + temozolomide treatment (58-60 Gy radiation with temozolomide 75 mg/m2 daily during radiation)
Patients who are receiving chemotherapy and radiation therapy
Neurologic deterioration (long tract signs, cranial nerve signs or ataxia) consistent with radiation necrosis or radiation induced injury
MR imaging (MRI) with findings considered consistent with radiation induced injury or radiation necrosis as confirmed by the study radiologist
Current chemotherapy or radiation therapy; participants in study may still be receiving hormone or Herceptin treatment
Must be referred to radiation oncology clinic
Patients suffering from dysphonia after radiation therapy for glottic carcinoma will be included in the study
Patients fewer than 1 year out from completion of radiation therapy will be excluded
Patients with lung or esophageal cancer stages I through IIIB who are going to receive at least 5 weeks of daily thoracic radiation therapy with or without chemotherapy in the department of radiation oncology at M. D. Anderson Cancer Center (MDACC) and have an eligible and consenting family caregiver living with the patient while he/she receives treatment (i.e., adult child, sibling, parent)
Prior radiation therapy is allowed provided that no radiation therapy was administered to the urinary bladder.
Prior radiation therapy above the umbilicus
Patient is not eligible if radiation was given to the only site of measurable disease unless there has been subsequent disease progression at that site, or a biopsy of that site showed viable tumor at least 4 weeks after radiation was completed. Patients must not have received small field (focal) radiation for a minimum of 2 weeks prior to study entry. A minimum of 6 weeks is required following prior large field radiation therapy (i.e. TBI, craniospinal therapy, whole abdomen, total lung, > 50% marrow space)
Plan to receive radiation therapy, or within 3 days of starting radiation therapy
For the esophagitis arm, any patient with thoracic malignancies, which will receive radiation alone or concurrent chemo/radiation; radiation dose must be >= 45 Gy; for the esophagitis arm, induction chemotherapy is allowed
Patients must not have had previous radiation therapy to the mediastinum or lungs
Planned stereotactic body radiation therapy (SBRT)
No prior history of radiation therapy
Prior history of radiation therapy
Have a plan to receive a continuous course of conventional external beam irradiation delivered by intensity-modulated radiotherapy (IMRT) as single daily fractions of 2.0 Gy to 2.2 Gy with a cumulative radiation dose ?55 Gy and ?72 Gy. Planned radiation treatment fields must include at least two oral sites (buccal mucosa, floor of mouth, ventral/lateral tongue, soft palate). [Note: the independent RTQA consultant must confirm that the planned radiation treatment meets the protocol criteria]
Has oral mucositis (of any severity) prior to initiation of radiation therapy
Were treated with ? 10 Gy of chest radiation therapy (RT) (recent revision with a lower dose threshold)
Radiation to both breasts
Women who have had radiation to both breasts
Patients must have a history of stage 0, I, II or III colon or rectal adenocarcinoma that has been treated per standard care with resection alone or in combination with radiation or chemotherapy; adjuvant chemotherapy and radiation therapy (RT) treatment must have been completed at least 30 days prior to registration
Women who have had radiation to both breasts
Prophylactic medication for the prevention of nausea and vomiting 24 hours prior to the start of radiation therapy through the full course of radiation therapy is prohibited, with the exception of the study drug; corticosteroids will be allowed for treatment of cerebral swelling
History of radiation therapy
Radiation within 14 days of starting study treatment
Clinical treatment plan calls for a minimum of 50 Gy cumulative radiation dose administered via continuous course of external beam irradiation to the oral cavity and/or oropharynx via intensity-modulated radiation therapy [IMRT] and/or image-guided radiation therapy [IGRT], combined with conventional or weekly/tri-weekly cisplatin or carboplatin chemotherapy regimen.
History of cranial radiation therapy
Prior radiation to the cranium
planned treatment course to include Cisplatin and radiation therapy, cumulative prescription dose between 50-70 Gy
Patients with any history of prior radiation therapy in the affected breast
Patients receiving stereotactic body radiation therapy
There are no limits on prior therapy; patients are allowed to have prior systemic therapy, radiation therapy, radiofrequency ablation, catheter-based therapies, and surgery; patients are allowed to have concurrent chemotherapy with radiation treatment
Participants must be evaluated by radiation oncology and deemed to be a candidate for stereotactic body radiation therapy for NSCLC
Patients who are offered radiotherapy using a 5-fraction stereotactic body radiation therapy course, at the recommendation of the treating radiation oncologist
Prior radiation therapy which would provide significant dose overlap with the planned target volume(s) delivered within 30 days of enrollment or registration
Contraindicated for radiation therapy
No prior history of chest wall radiation
Prior radiation therapy treatment in the target lobe
Histologic proof of malignancy suitable for thoracic radiation therapy
Patients should not have received chemotherapy or radiation therapy (localized radiation therapy is allowed to non-evaluable sites) between prior 123I-MIBG scan and 18F-MFBG administration
Study participants must have histologically confirmed primary malignant bone tumor in the sacrum for which surgery and radiation or radiation alone are planned
Pregnancy if the patient is receiving radiation therapy
Radiotherapy is planned as definitive therapy for prostate cancer; for patients not treated at NCI Radiation Oncology Branch (ROB) patients must have a radiation oncologist who is willing to collaborate with the ROB and provide documentation of treatment
Subjects must not have been treated with chemotherapy or radiation for another malignancy within the preceding 6 months
Prior radiation therapy to a symptomatic site of metastatic disease is allowed but patients must have discontinued/completed radiation therapy at least 2 weeks prior to entering the study, and have recovered from adverse events due to that treatment
May undergo radiation therapy
Patients expected to be treated with radiation therapy, chemo-radiation therapy, or chemotherapy
The subject has had preoperative radiation therapy
Previous radiation exposure precluding radiation therapy
No prior radiation to the same area
Prior chest radiation or radiation for esophageal cancer
Subjects who have been treated with radiation therapy on the chest
Untreated low grade gliomas will be imaging-defined gliomas that have not yet been exposed to radiation or systemic chemotherapy; those exposed to therapy will have had radiation and/or systemic chemotherapy more than 1 month prior to scans
Prior therapies including involved field radiation therapy
ARM II ONLY: For patients status post radiation therapy for prostate cancer, any PSA increase from post radiation therapy nadir OR
Patients must be planned for at least 45 Gy of thoracic radiation
There are no limits on prior therapy; patients are allowed to have prior chemotherapy, radiation therapy, and surgery; patients are allowed to have concurrent chemotherapy with radiation treatment; patients are allowed to have chemotherapy after radiation treatment; patients are not allowed to have planned lung resection after radiation
Patients will typically be enrolled on this trial prior to beginning the radiation treatment course; however, if a patient has had a SPECT/CT 99mTc-MAA and 99mTc-DTPA scan as part of routine medical care within 6 weeks prior to initiation of radiation treatment, he/she is eligible for trial enrollment up to the last day of the radiation treatment course
Patients receiving < 45 Gy radiation
History of radiation therapy for cancer treatment
No prior radiation therapy
The patients must have no prior chemotherapy or radiation therapy as treatment
Patients who will be treated with radiation therapy or concurrent chemoradiation therapy
Radiation therapy: may not have had radiation therapy to area of tumor planned to be resected w/in 28 days
Tumor progression or recurrence within 6 months of the last dose of platinum-based therapy in the adjuvant (that is, with radiation after surgery), primary (that is, with radiation), recurrent, or metastatic setting.
Subjects ADT naive or subjects who are already on ADT treatment and scheduled to receive radiation therapy for their adenocarcinoma of prostate are eligible. An 8-week course of ADT is required to be completed prior to NBTXR3 administration and initiation of radiation therapy .
Patients must have previously received at least one line of therapy for their advanced lung cancer; there are no restrictions on the maximum number of prior therapies allowed
Prior experimental (non-Food and Drug Administration [FDA] approved) therapies and immunotherapies are allowed; patients must not have received these therapies for 4 weeks prior to the initiation of study treatment and must have recovery =< grade 1 from any adverse events of these therapies (other than alopecia); prior treatment with any PARP inhibitor or any anti-PD-1/anti-PD-L1 antibody is NOT allowed
Patient has persistent toxicities from prior MDS therapies which are determined to be relevant by the Investigator.
Patients may have had 0-4 prior therapies\r\n* Prior chemoembolization or local ablative therapies are permitted if completed >= 6 weeks prior to study enrollment\r\n* Prior temozolomide is permitted
Receipt of treatment with immunotherapy, biological therapies, targeted small molecules, hormonal therapies within 3 weeks of scheduled C1D1 dosing.
Has receiving immunosuppressive or other contraindicated therapies within the excluded time frame from entry
No limit on number of prior therapies
Co-administration of anti-cancer therapies other than those administered in the study
Must have been treated with at least 2 prior systemic therapies.
Participants are permitted to have any number of prior therapies prior to enrollment
Patients are eligible for available approved standard therapies
Patient have received anti-cancer therapies within defined time frames prior to the first dose of study treatment
Requirement of active receipt of systemic therapies concurrent with SBRT (concurrent hormonal therapies are allowed)
Not amenable to approved therapies
Have discontinued all previous therapies for cancer.
Any number of prior chemotherapies and targeted therapies are allowed
Melanoma after failure of available therapies
Any number of prior systemic therapies.
Discontinuation of previous cancer therapies at least four (4) weeks prior to treatment in this study.
Other therapies: Prior experimental (non-Federal Drug Administration [FDA] approved) therapies (other than drugs that share the same target) and immunotherapies are allowed; patients must not have received these therapies for 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies
Active residual toxicity from prior therapies.
Treatment with any of the following prior therapies:
All subjects' cancer must have progressed after treatment with standard therapies or have no appropriate available therapies.
At least one line of prior systemic therapy for metastatic or recurrent breast cancer (there is no limit to the number of prior therapies)
Prior anti-cancer therapies for current malignancy
Patients with known oncogenic mutations for which there are approved therapies must have documented intolerance or disease progression for the approved therapies for their mutation. For Other Indications
two prior hormonal therapies;
No limit to number of prior therapies
There is no limit to number of prior therapies
Patients who have received other cell therapies
Part C) Triple-negative disease and received 2-4 prior non-hormonally-directed therapies in the MBC setting (not enrolling new patients);
Naive to prior systemic anti-cancer therapy for melanoma (example: chemotherapy, hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies) except adjuvant treatment with interferon (IFN), interleukin (IL)-2, or vaccine therapies or herbal therapies
Patients may not receive any other anti-cancer therapies, within 28 days prior to registration and throughout the duration of this trial
PHASE I: No limit on the number of prior systemic therapies for metastatic disease
Received anti-cancer therapies within the following time frames prior to the first dose of study treatment:
Patients are not eligible if they are using any other approved or investigational anti-neoplastic therapies or any other investigational therapies for any other reason.
Not amenable to approved therapies
There is no limit on the number of prior therapies
Must have received first line chemotherapy; no upper limit to number of prior therapies
Patients cannot have received any other immunomodulatory therapies (including vaccines) as treatment for this or any other cancer.
There is no limit on prior systemic or IT therapies
Patients with a history of prior adoptive cell therapies.
Received chemotherapy, radiotherapy, immunotherapy, or any investigational cancer therapies within 28 days prior to the first dose of enzalutamide and/or CORT125281, or treatment with such therapies is planned during protocol treatment
The participant may have no more than 2 prior lines of systemic therapies (neoadjuvant and adjuvant therapies will not be considered as a prior line of therapy) for advanced or metastatic disease and is suitable to receive gemcitabine and docetaxel therapy. All previous therapies must have completed ? 3 weeks (21 days) prior to first dose of study drug.
Any number of prior therapies are allowed
EXCLUDED THERAPIES AND MEDICATIONS FOR CANCER
There are no specific restrictions for therapies to treat cGVHD
Patients can have any number of prior therapies and any amount of time period from the last therapy as long as they have complete response as seen in PET/CT at the time of enrolment
Prior systemic, regional and radiation anticancer therapies must have been completed at least three months prior to enrollment; prior therapies (including anti-PD-1 inhibitors) is allowed provided three months have elapsed from last dose
Any number of prior therapies is allowed
Unlimited prior therapies allowed
Patients may have received an unlimited number of prior therapies
Relapse following first line immunotherapy or chemoimmunotherapy; there is no upper limit to the number of therapies received prior to study entry; prior therapies may include high-dose therapy with autologous stem cell rescue
Patients may or may not have received prior therapy for their recurrent/metastatic disease\r\n* NOTE: There is no limit to the number of prior therapies for stage IV disease\r\n* NOTE: Patients should not be a candidate for curative surgical treatment or radiation (palliative radiotherapy is permitted)
Patients on bisphosphonates or RANK-L inhibitors may continue receiving these therapies during study treatment; there is no washout period required between the last dose of these therapies and the start of abemaciclib
Ongoing or planned administration of anti-cancer therapies other than nivolumab
There is no limit on number of prior therapies
Hormonal tumor therapies should not be administered within 14 days of registration; exceptions may be discussed with the PI
PCSPES or PCx products; other herbal therapies or supplements will be considered by the principle investigator on a case-by-case basis based on their potential for hormonal or anticancer therapies
Subjects must have received no prior therapies for this disease
The number of prior therapies is restricted as follows:\r\n* Zero or one prior therapies during the preceding one year; this serves to limit the treatment cohort to patients with either only slowly progressive disease, or up to one prior therapy\r\n* No prior PD-1 or PD-L1 antibody therapies are allowed\r\n* Prior IL-2 is allowed, if it finished more than 1 year prior
Symptomatic subjects who accept treatment with approved palliative or life-prolonging systemic therapies, including docetaxel and cabazitaxel chemotherapy; (Note: subjects who refuse chemotherapy or are not symptomatic or in immediate need for standard systemic therapies may be included)
Subjects who have received anti-CD 19 targeted therapies, chimeric antigen receptor T-cell or other cellular therapies for the treatment of their lymphoma .
Any prior number of prior therapies, including prior immunotherapy, is allowed
Any number of prior therapies (including none) is permitted; the last dose of systemic therapy (include targeted therapies) must have been given at least 4 weeks prior to initiation of therapy; patients receiving carmustine (BCNU) or mitomycin C must have received their last dose of such therapy at least 6 weeks prior to initiation of therapy
Patients may be treatment naive or have received any number of prior therapies\r\n* NOTE: Prior immunotherapy is contraindicated and not permitted
Patients may not have received prior HER2 directed therapies
Receipt of therapies or procedures prior to first dose including:
Prior use of other retinoid therapies in the 3 months prior to enrollment in the study
Any number of prior therapies as long as patients have adequate performance status and meet all other eligibility criteria
Histiocytic disorder must be (a) multi-system disease or (b) disease that is recurrent or refractory to standard therapies, or (c) single-system disease that is unlikely to benefit from conventional and less toxic therapies, based on the best available evidence (for example, central nervous system [CNS] or cardiac infiltration, retroperitoneal fibrosis, prior chemotherapy, or other medical history or co-morbidities, etc)
Subject who received any therapies intended to treat malignancy within 21 days of first receipt of DS-3032b
Required washout period for prior therapies Topical therapy: 2 weeks
Co-administration of anti-cancer therapies other than those administered in this study
Any number of prior therapies as long as patients have adequate performance status and meet all other eligibility criteria
Patients may be previously untreated or have received up to 3 prior systemic therapies for metastatic disease; prior radiation therapy (any number) and interferon use in the adjuvant or metastatic disease settings is permitted (in this trial interferon is mainly used to enhance or initiate immune responses to MK-3475); vaccine therapy will not be counted as systemic therapy; all prior therapies must have been discontinued for at least 4 weeks; a 2 week washout for kinase inhibitors is acceptable
Patients may have had any number of prior systemic therapies; patients need not have exhausted standard therapy for their disease, but must be stable and must not have actively progressing
Any number of prior therapies is allowed
Prior therapies:\r\n* For patients stratified to the untreated arm:\r\n** Untreated patients should have received zero prior therapies for metastatic disease\r\n** They may have received prior adjuvant chemotherapy and/or radiation therapy, but not within 6 months prior to treatment\r\n** They may have received prior palliative radiation therapy for unresectable disease, but without any systemic chemotherapy, even as a radiosensitizer\r\n* For patients in the previously treated arm:\r\n** Previously treated patients may have received any number of prior therapies\r\n** Patients who received prior adjuvant chemotherapy and/or radiation therapy within 6 months of treatment will be considered previously treated\r\n*** Patients may have received any prior therapies EXCEPT prior therapy with a PARP inhibitor\r\n** Timing of prior therapies:\r\n*** At least 14 days must have passed since all prior anti-cancer therapy, including chemotherapy, biological therapy, or radiation therapy\r\n*** However, at least 28 days must have passed since any prior antibody-based therapies (such as, but not limited to cetuximab or bevacizumab)\r\n*** Additionally, at least 28 days must have passed since any prior investigational agent\r\n*** All patients must have completely recovered from all transient side effects related to prior therapies\r\n**** However, any side effects that are expected to be more durable or even permanent (e.g., neurotoxicity or ototoxicity) must have resolved to at least grade 1
No limitations on prior therapies
Arms B1-B6: Has undergone 1-3 previous regimens of cytoreductive chemo-therapies Arm B7: with no prior exposure to anti-PD-(L)1 therapies and have received no prior systemic treatment for RM SCCHN
MDS at any stage; prior therapies allowed
First or later relapse AND has received at least 2 prior therapies (one of which can be frontline therapy) or
Receipt of all standard therapies for the tumor type:
Refractory disease, having failed available therapies
Arm 1: Subjects must have received at least one prior therapy and a maximum of three prior therapies
Failed available therapies (pancreatic cancer may be treated without previous therapies)
Any previous antitumor therapies for the current cancer event
Failed >= 2 prior systemic therapies
Prior treatment within 21 days of the first dose of study drug with any other chemotherapy, immunotherapy, biologic therapy, vaccine therapy, or investigational treatment, or failure to recover from adverse effects of prior therapies administered over 4 weeks prior to study day 1; all toxicities from prior therapies must be =< grade 1 (or =< grade 2 for alopecia or peripheral neuropathy); prior systemic treatment in the adjuvant setting is allowed
Participants requiring the use of anti-tumor necrosis factor (anti-TNF) therapies, such as infliximab, or has received treatment with anti-TNF therapies within 5 half-lives of the drug
Any number of prior endocrine therapies is allowed and must be discontinued prior to randomization
Any number of biologic therapies (e.g., bevacizumab) or immunotherapies is allowed in the absence of co-administered chemotherapy and must have been completed >= 28 days prior to randomization
No more than two (2) prior anti-cancer therapies for aBC
All patients must have received, and be relapsed/refractory to at least one line of systemic therapy\r\n* NOTE: This does not include surgery or radiation alone; patients may have received any number of systemic therapies\r\n* NOTE: For patients with aggressive lymphoma, there should be no other standard therapies that would confer survival benefit
Subjects must have progressive cancer at the time of study entry; prior experimental (non-Food and Drug Administration [FDA] approved) therapies (other than drugs that share the same target) and immunotherapies are allowed; patients must not have received these therapies for 30 days or five half-lives of the drug (whichever is less) prior to the initiation of study treatment; toxicities from these therapies should have recovered to =< grade 1, with the exception of stable chronic grade 2 that is not overlapping with presumed toxicities of olaparib
There is no limit to number of prior therapies
Discontinuation of other therapies (except corticosteroids) for the treatment of NF2\n             and resolution of any acute toxic effects of prior therapies
Progression on, or intolerance of, or ineligibility for all standard therapies
There is no limit to the number of prior therapies
Patients treated with other secondary hormonal therapies
Patients with prior investigational therapies within 4 weeks before treatment with\n             APC-100
1c. Colorectal Cancer -Enrollment Completed Metastatic or recurrent; prior treatment progression during, after, or intolerant following the last administration of approved standard therapies (required therapies apply).
Must have received 1 or 2 prior anti-angiogenic therapies.
Any number of prior therapies (ie, chemotherapy and/or ROS inhibitor therapies).
at least 2 HER2-directed therapies for advanced disease
Inadequate response, relapse, and/or unacceptable toxicity with ? 1 prior systemic, surgical, or radiation cancer therapies.
Use of certain investigational therapies within 21 days prior to enrollment
Participants in Stage 1 (Safety Evaluation) receiving erlotinib: No limit to the number of prior therapies (except for EGFR TKIs).
Inadequate response, relapse, and/or unacceptable toxicity with one or more prior systemic, surgical, or radiation cancer therapies, and for whom curative standard therapy is not an option (except patients with NSCLC who must have experienced either an inadequate response, relapse, and/or unacceptable toxicity with two or more prior systemic, surgical, or radiation cancer therapies)
Any number of prior therapies is allowed
Prior experimental (non-Food and Drug Administration [FDA] approved) therapies and immunotherapies are allowed; patients must not have received these therapies for 4 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies
Any prior use of hormonal therapy, including:\r\n* Gonadotrophin releasing hormone (GNRH) agonists or GNRH antagonists (e.g., leuprorelin, degarelix)\r\n* Antiandrogens (e.g., bicalutamide, flutamide, nilutamide)\r\n* Novel androgen-directed therapies (e.g., abiraterone, enzalutamide)\r\n* Any estrogen containing compounds\r\n* 5-alpha reductase inhibitors (e.g., finasteride, dutasteride)\r\n* PC-SPES or PC-x products; other herbal therapies or supplements will be considered by the principle investigator on a case by case basis based on their potential for hormonal or anti-cancer therapies
Patients must have received at least 2 prior therapies.
Other investigational therapies
Any other previous antitumor therapies for the current cancer event
Have mCRC that has been treated with currently approved standard therapies
Failure, ineligible or intolerant of approved therapies; any number of prior systemic therapeutic regimens for unresectable stage III or stage IV melanoma; this includes chemotherapy, immunotherapy, pathway inhibitors, biochemotherapy, or investigational treatments; patients may also have received therapies in the adjuvant setting
Co-administration of anti-cancer therapies other than those administered in this study
Ongoing or planned administration of anti-cancer therapies other than those specified in this study
May have received prior therapies for advanced or metastatic disease
Received any of the following prescribed medications or therapies in the past:
Must have received at least 2 prior approved therapies
Any number of prior therapies other than oxaliplatin is allowed
Herbal therapies, with an antitumor effect.
Ongoing or planned administration of anti-cancer therapies other than those specified in this study
Patient must have received at least one, and no more than two prior systemic therapies for metastatic cancer
Patients who have received previous systemic therapies including TKI inhibitors are eligible.
Participants are permitted to have any number of prior therapies prior to enrollment
Other available therapies have failed to cure the cancer
Taking investigational or commercial agents or therapies with the intent to treat the subject's malignancy other than those therapies permitted
RESTRICTED THERAPIES:
At least 1 prior treatment (no restriction to number of prior therapies)
Participants may have received any number of prior therapies as long as they have adequate performance status and meet all other eligibility criteria
Patients may have received any number of prior CNS directed therapies - there are no limitations
Patients must have received at least one prior line of therapy for their advanced lung cancer but there is no restrictions on the maximum number of prior therapies allowed
Prior treatment with embolization of ablative therapies is allowed if measurable disease remains outside of the treated area or if there is definite progression of the treated lesions; there is no limit on the number of prior procedures
Must have received first line chemotherapy; no upper limit for the number of prior therapies
Participants may have received up to 2 prior cytotoxic chemotherapies; there is no limit to the number of lines of prior biologic or hormonal therapies they may have had; patients must be platinum resistant
Participants may have received any number of prior cytotoxic chemotherapies; there is no limit to the number of lines of prior biologic or hormonal therapies they may have had; patients may be platinum-sensitive or resistant or refractory
Received any of the following antitumor therapies
Prior therapies:
Received other therapies as follows:
Must have received at least 2 prior therapies approved for CRPC; including a prior AR inhibitor (e.g., enzalutamide or apalutamide). (Part 1 only)
Patients who have received more than two prior therapies
Receipt of any biological or immunological-based therapies (including experimental therapies) for leukemia, lymphoma, or myeloma (including, but not limited to, MAb therapy such as rituximab, or cancer vaccine therapies) within 28 days or 5 half-lives, whichever is shorter, prior to the first dose of MEDI-551
Patients may have received any number of prior therapies, including monotherapy with liposomal doxorubicin or bevacizumab
Patient have received anti-cancer therapies within the following time frames prior to the first dose of study treatment:
At least three weeks from any non-anti-EGFR therapy prior to start of study treatment; any number of prior therapies is permitted
Immunosuppressant therapies other than allowed background therapy
Most prior therapies and prior targeted therapy are allowed and these specific therapies are detailed in the protocol.
Patient must have received at least one line but less than three lines of prior systemic therapies and have either progressed or intolerant to prior therapies; patients who have received adjuvant/neoadjuvant therapy within last one year will be eligible as well
Must have received at least 4 prior therapies, including an alkylating agent (unless not clinically indicated), proteasome inhibitor, an immunomodulatory (IMiD) and CD38 targeted therapy. At least 3 prior therapies where CD38 targeted therapies are not approved, not commercially accessible, contraindicated or refused by subject. DLBCL Dose Expansion Arm:
1 to 2 prior therapies
Excluded previous therapies and medications:
At least 14 days between ibrutinib initiation and last cancer therapy; any number of prior cancer therapies is permitted; patients otherwise fit for blood or marrow transplantation (BMT) should receive second-line chemotherapy before considering enrollment
Prior treatment with any number of immunotherapies (e.g., IL2, ipilimumab), targeted therapies (e.g., vemurafenib) are permitted but no more than one 1 prior chemotherapy
For Phase Ib, there is no restriction on the number of prior therapies for recurrent or metastatic disease
Anticipated or ongoing administration of anti-cancer therapies other than those administered in this study
All subjects must have advanced solid tumors that have returned after treatment with established approved therapies or be intolerant of established therapies
For investigational anti-cancer therapies, the interval will be determined in consultation with the Medical Monitor.
< 28 days for any antibodies or biological therapies
Patient has persistent toxicities from prior anti-leukemic therapies which are determined to be relevant by the Investigator.
Use of antineoplastic therapies within 21 days before day 1.
Receipt of treatment with immunotherapy (including interferons, interleukins, immunoconjugates), biological therapies (including monoclonal antibodies or other engineered proteins), targeted small molecules (including but not limited to kinase inhibitors), hormonal therapies (except for gonadotropin releasing hormone agonists/antagonists for prostate cancer which may be continued while on study) within 3 weeks of scheduled dosing day 1.
Being treated with other anti-cancer therapies (approved or investigational).
Concurrent administration of any anti-cancer therapies other than those administered in this study
Discontinuation of all other therapies for treatment of iNHL ? 3 weeks before Visit 2
No limitations on prior systemic or intrathecal therapies
Subject has not discontinued all previous systemic therapies for cancer including chemotherapy, immunotherapy, or biological therapies for at least 14 days prior to the initiation of ASP4132.
Has received other anti-cancer therapies other than IMO-8400 since enrolling in Protocol 8400-401.
Being treated with other anti-cancer therapies (approved or investigational)
Ongoing adverse events from surgery or prior anti-cancer therapies, including radiation, targeted, or cytotoxic therapies
Co-administration of anti-cancer therapies other than those administered in this study
Received and failed all known effective therapies for their disease;
Anticipated or ongoing administration of anti-cancer therapies other than those administrated in this study
Parts A,B: The presence of a solid, malignant tumour, excluding lymphoma, that is resistance to standard therapies or for which no standard therapies exist.
Must not be receiving other anti-cancer therapies (except somatostatin analogues, which may be allowed)
Some prior cancer therapies are not consistent with eligibility; specifically:
May have up to three biological therapies
Patients planning on receiving other anti-cancer therapies while on this study
Patient has received any of the following therapies:
Patients receiving other investigational therapies
Part B: Candidate for experimental therapy after standard therapies used or non-eligible for standard therapies. Histological or cytological evidence of 1 of the 5 tumor types:
Received prior therapies including:
Less than 4 prior systemic cancer therapies (with the exception of hormonal agents), including experimental agents, prior HER-family TKI therapies, and prior docetaxel and other taxane therapy; there are no limits to the number of prior therapies for Part 1
6-60 months post-treatment (surgery, chemotherapy, radiation therapy, and/or maintenance therapies) for cancer; time frame applies to most recent completion of treatment if participant had a cancer recurrence; it is acceptable to be on hormonal therapies
COHORT A SPECIFIC INCLUSION: Histologically confirmed IDHwt, retinoblastoma (RB) intact, grade II or III glioma that has recurred after first line therapy (consisting of at least maximum feasible surgical resection and radiation therapy); there is no limit on the number of prior therapies or types of therapies patients can have received
No limit on number of prior therapies
Have received more than 2 prior therapies for ED-SCLC (including immunotherapy, targeted therapies, or chemotherapy)
Patients on anti-hormonal therapies (e.g., anti-estrogens for breast cancer) or other maintenance therapies will be eligible.
Any number of prior therapies are allowed
Completed treatment for breast cancer (except hormonal therapies) within 12 months.
Subject has not started any new systemic immunosuppressive therapies within 2 weeks prior to enrollment
Failure of previous HCV therapies
Prior experimental (non-Food and Drug Administration [FDA] approved) therapies and immunotherapies are allowed; patients must not have received these therapies for 3 weeks prior to the initiation of study treatment and must have full recovery from any acute effects of these therapies
Patients can have had any number of prior therapies, including but not limited to molecularly targeted therapies and anti-angiogenic therapies, however they must have had prior chemotherapy with either temozolomide or lomustine
Patients must not have received any study therapies prior to registration
Has undergone ? 2 prior standard therapies
There is no limit to the number of prior therapies
Prior sorafenib use > 60 days and/or grade 3 or 4 sorafenib related toxicity; note that prior chemotherapy for HCC or a different cancer is allowable
One prior line of therapy which must include sorafenib or participant must have progressed or been intolerant to sorafenib for participants not eligible for transarterial chemoembolization. Participants who had sorafenib for locally advanced disease or are intolerant to sorafenib are eligible. Participants may have had clinical progression only following sorafenib or local therapy.
Presence of at least one measurable lesion according to RECIST v1.1. c-i) FGF401 single agent-Phase I and Phase II, Group 3: Patients with HCC or advanced solid tumors, who have progressed despite standard therapy or are intolerant of standard therapy, or for whom no standard therapy exists. c-ii) FGF401 single agent-Phase II, Groups 1 and 2: HCC patients previously treated with sorafenib for advanced HCC with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment c-iii) FGF401 in combination with PDR001:Advanced HCC patients who have received up to 2 previous lines of systemic treatment and one treatment must have included sorafenib with documented disease progression during or after discontinuation of sorafenib treatment, or intolerance to sorafenib treatment
Previous treatment with vemurafenib or any other BRAF inhibitor (prior sorafenib is allowed)
Previous BRAF inhibitor use such as vemurafenib, GSK2118436 or sorafenib
For patients that have refused treatment with sorafenib, the benefits of sorafenib have been discussed in detail with the patient.
Immunotherapy-naive and have either progressed on, are intolerant to, or refused treatment with sorafenib. Subjects who receive treatment with systemic therapies other than sorafenib are not eligible.
Prior treatment with a BRAF inhibitor such as vemurafenib or dabrafenib (previous treatment with sorafenib is allowed)
Patients must be off sorafenib for at least four days prior to TACE treatment
Participants who have received prior sorafenib or anti-PD1 therapy for HCC
Inability to tolerate first-line treatment with sorafenib (e.g., unacceptable toxicity), tumor progression on sorafenib, patient preference to stop sorafenib and for alternative therapy/trial, or patient preference to forgo sorafenib for alternative therapy/trial
Patients who have received sorafenib or other systemic therapies for treatment of HCC in the past
Have documented objective radiographic progression after stopping treatment with sorafenib or else intolerance to sorafenib; intolerance to sorafenib is defined as: Common Terminology Criteria for Adverse Events (CTCAE) grade >= 2 drug-related adverse event(s) which both a) persisted in spite of comprehensive supportive therapy according to institutional standards and b) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level; patients treated on sorafenib as the last treatment may start pembrolizumab at least 14 days after the last dose of sorafenib
Had prior systemic therapy for HCC other than sorafenib, or intercurrent local therapy to the liver tumor between sorafenib and study drug
Has received sorafenib within 14 days of first dose of study medication
Documented progression or intolerance to sorafenib as demonstrated by:\r\n* Radiographic (by modified [m]RECIST) or symptomatic progression on/after sorafenib\r\n* Intolerance to sorafenib consisting of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater during drug-related adverse event which persisted in spite of comprehensive supportive therapy according to institutional standards AND persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily)
Patients may receive concurrent capecitabine or sorafenib at the discretion of the treating physicians
Known or presumed intolerance of pemetrexed or sorafenib
If sorafenib was previously administered, intolerance to sorafenib
Patients who have received sorafenib or other systemic therapies for treatment of HCC in the past
Prior 90Y TARE or sorafenib is not allowed
Known or suspected allergy or hypersensitivity to sorafenib
Inability to tolerate first-line treatment with sorafenib (e.g., unacceptable toxicity), tumor progression on sorafenib, patient preference to stop sorafenib and for alternative therapy/trial, or patient preference to forgo sorafenib for alternative therapy/trial\r\n* Note:\r\n** Unacceptable toxicities due to sorafenib include, but are not limited to, the following drug-induced adverse events including: hepatitis, skin rash (grade 3 or higher), hypertension (grade 3 or higher), hand-foot skin reaction (grade 3 or higher), QT prolongation (grade 3 or higher), and/or diarrhea (grade 3 or higher)\r\n** Patient preference to stop sorafenib for alternative therapy/trial will include the following indications: the aforementioned adverse events at lesser grades for which the patient is unwilling to continue therapy, as well as situations in which the patient deems the side effects to be intolerable with their quality of life; examples include, but are not limited to, intolerable nausea, vomiting, abdominal pain, fatigue, loss of appetite, and weight loss\r\n** Patient preference to forgo sorafenib for alternative therapy/trial is based upon the patients' right for autonomy; this allows them to refuse or choose their treatment; the practitioner will always act in the best interest of the patient and recommend that the patient start with known life-prolonging therapies before enrolling in a clinical trial of an investigational agent that has not been determined to be safe and effective in patients with liver cancer
Sorafenib\r\n* Creatinine (Crt) < 1.5 X ULN
History of hypersensitivity to sorafenib for vemurafenib/sorafenib arm
Patients must have received prior systemic sorafenib treatment for HCC with documented progression during or after discontinuation of sorafenib treatment (for France only: patients must have received at least 8 weeks of prior sorafenib treatment), or are intolerant to sorafenib (defined as documented Grade 3 or 4 adverse events that led to sorafenib discontinuation),.
Patient is receiving sorafenib (Nexavar) as a monotherapy in their originating protocol. Patients who were being treated with sorafenib (Nexavar) in combination with other chemotherapies in the original study, but continued on single agent sorafenib (Nexavar) after discontinuation of the combination agent will be eligible.
Patients who are receiving concurrent combination with sorafenib (Nexavar) and capecitabine in their originating Study 12444 (RESILIENCE) will be eligible.
Expansion cohort (HCC): histologically or cytologically confirmed diagnosis of hepatocellular carcinoma who are Child-Pugh class A and who were previously treated with sorafenib or refused sorafenib
Hepatocellular carcinoma cohort specific criteria:\r\n* Patients must have a histologically proven diagnosis of hepatocellular carcinoma that is not amenable to curative surgical therapeutic options\r\n* Patients must not be good candidates for locoregional therapy as determined by the investigator (ie diffuse multifocal disease, vascular involvement, etc)\r\n* Patients must have had evidence of radiologic progression on sorafenib or have had intolerance to sorafenib as defined by the recurrence of clinically significant toxicities despite a minimum of one dose reduction and appropriate supportive care; patients who refuse sorafenib are eligible with documentation of refusal by the treating physician\r\n* Patients may have received other treatment for HCC such as embolization, chemoembolization, intra-arterial chemotherapy, ethanol injection, ablative therapy, cryosurgery, or other locoregional or targeted therapy\r\n* Patients must have a Child Pugh score of 7 points or less \r\n* International normalized ratio (INR) =< 2.3 or prothrombin time =< 6 seconds above control\r\n* Patients with hepatitis B infection must be on appropriate anti-viral therapy
Systemic therapy with sorafenib or other systemic chemotherapeutic agent(s) less than 1 week prior to first planned DEB-TACE
No prior systemic cytotoxic chemotherapy or targeted therapy (including sorafenib) for HCC
Pretransplant treatment with sorafenib tosylate (sorafenib) not > 12 months (not exceeding 12 months of treatment, total)
Prior use of any systemic chemotherapy for HCC, with the exception of sorafenib
Has documented objective radiographic progression during or after treatment with sorafenib or intolerance to sorafenib.
Has received sorafenib within 14 days of first dose of study drug.
Has had prior systemic therapy for HCC in the advanced (incurable) setting other than sorafenib, prior to the start of study drug.
Must have progressed on, refused, or were intolerant of sorafenib.
Received prior sorafenib.
Subject must have received sorafenib treatment and either:
have had documented radiographic or symptomatic progression during or after sorafenib therapy; OR
be intolerant of sorafenib (defined as Grade 2 drug-related adverse event which 1) persisted in spite of comprehensive supportive therapy according to institutional standards AND 2) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily) AND/OR Grade 3 drug-related adverse event which 1) persisted in spite of comprehensive supportive therapy according to institutional standards OR 2) persisted or recurred after sorafenib treatment interruption of at least 7 days and dose reduction by one dose level (to 400 mg once daily); OR must have documented refusal of sorafenib;
Prior treatment with sorafenib or tivozanib.
Eligible to receive standard-of-care sorafenib
Prior systemic treatment for the treatment of HCC, including sorafenib
For Cohort 1: has documented objective radiographic progression after stopping treatment with sorafenib or else intolerance to sorafenib
For Cohort 1: has received sorafenib within 14 days of first dose of study drug
For Cohort 1: had prior systemic therapy for HCC other than sorafenib, or intercurrent local therapy to the liver tumor between sorafenib and study drug
Known intolerance to lenvatinib or sorafenib (or any of the excipients)
Has histopathologically or cytologically confirmed HCC, Child-Pugh Class A, with documented disease progression during or after discontinuation of sorafenib therapy, or intolerance of sorafenib therapy, and an ?-fetoprotein (AFP) ? 1.5x upper limit of normal
For patients in the sorafenib tosylate (sorafenib) cohort, no prior therapy with sorafenib is allowed and at least 1 line of prior therapy is required including prior: VEGF-targeting therapy (such as sunitinib, axitinib, tivozanib, bevacizumab), mTOR-targeting therapy (such as everolimus, temsirolimus), immunotherapy (such as anti-PD-1 or anti-PD-L1), cytokine therapy (such as interleukin-2, interferon-alpha [IFN-a]) or cytotoxic systemic chemotherapy allowed
Patients who have had prior anti-angiogenic therapy, including but not limited to sorafenib, brivanib, bevacizumab, or sunitinib; prior treatment with liver directed, ablative or surgical therapies will be permitted as long as there is documented progression justifying the need for starting sorafenib therapy
Patients with prior or current treatment of sorafenib are excluded
Histologically proven advanced MPM, advanced peritoneal mesothelioma (for dose escalation cohort only) or non-squamous NSCLC (stage IIIB/IV) who have not been treated with prior chemotherapy or immunotherapy, except that NSCLC subjects with EGFR mutant or ALK positive must have had an EGFR tyrosine kinase inhibitor (TKI) or ALK inhibitor and progressed or been shown to be intolerant of therapy prior to enrolling in this trial, if such ALK inhibitor and EGFR targeted therapy are approved and available in the country in which patients are being enrolled OR Histologically proven metastatic uveal melanoma who have not been treated with prior chemotherapy (MTD cohort only), OR Histologically proven HCC who have failed (PD and/or side effects-been intolerant of) treatment with sorafenib. Failure is defined as having progressed radiographically on, or been intolerant to prior systemic therapy. Intolerance is defined as discontinuation due to an AE(s) on prior systemic therapy that was unacceptable to the treating physician and / or patient, with or without dose interruption and modification. Failure requires at least 14 days of treatment with sorafenib, except for a subject that has had a severe allergic reaction to sorafenib at any time, even less than 14 days of treatment with sorafenib and thus it would be imprudent to re-challenge them with that agent. Cirrhotic status of Child-Pugh grade A-B7 must be present. Child-Pugh status should be determined based on clinical findings and laboratory data during the screening period (Appendix E). Subjects on anti-coagulants are to receive 1 point for their INR status, as they are presumed to have a <1.7 baseline PT/INR.\, OR Histologically proven high-grade glioma who have failed (PD and/or side effects) treatment with radiotherapy ± temozolomide, OR Sarcomatoid cancer of any line.
Prior systemic therapy for the treatment of HCC, including sorafenib
Prior use of sorafenib
Prior treatment with sorafenib as single agent or in combination, with no less than 200 mg once every other day dose of sorafenib, with radiologic evidence of progression of disease
The patient has received any investigational agents within 4 weeks prior to their first dose of sorafenib
Failure to prior treatment with sorafenib (defined as documented radiological progression according to the radiology charter). Randomization needs to be performed within 10 weeks after the last treatment with sorafenib.
Tolerability of prior treatment with sorafenib defined as not less than 20 days at a minimum daily dose of 400 mg QD within the last 28 days prior to withdrawal.
Sorafenib treatment within 2 weeks of randomization.
Prior systemic treatment for HCC, except sorafenib.
Permanent discontinuation of prior sorafenib therapy due to sorafenib related toxicity.
Intolerance of prior treatment with bevacizumab, pazopanib, sorafenib, or sunitinib; Note: subjects who required a dose reduction of pazopanib, sorafenib, or sunitinib during prior therapy MAY be eligible if they tolerated the agent after dose level reduction (to a minimum of dose level -2 as defined in this protocol)
Patients may have received any prior therapy deemed necessary for induction of remission except for patients whom have progressed while on sorafenib; patients who have responded to sorafenib previously are eligible for enrollment on the protocol
For Parts A & B: Have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment. For Part C: not received previous systemic treatment. For Part D: have received sorafenib and have progressed or were intolerant to sorafenib or are ineligible for sorafenib treatment or have not received prior systemic treatment.
For Parts A, B, and D: have discontinued sorafenib for at least 2 weeks
SORAFENIB ARM: platelets >= 75,000/mL
SORAFENIB ARM: history of hypersensitivity to sorafenib or any component of the formulation
Prior sorafenib is allowed as long as toxicity from ongoing is =< grade 2 and prior intolerance of 400 mg sorafenib PO daily is felt amenable, by the principal investigator, to supportive care measures or dose modifications
Documented progression on or after treatment with sorafenib, confirmed by the Investigator upon review of appropriate imaging documentation
Mandatory tumor biopsy at study entry (pre-randomization, unless already collected after sorafenib progression but within 3 months of enrollment and no systemic anticancer therapies received)
Prior systemic treatment for advanced liver cancer other than sorafenib-including therapy
Previous treatment with sorafenib for more than 4 weeks during the previous 2 months; prior sorafenib-related toxicity
For Part 1 and 2, the patient has unresectable disease and has been previously treated with sorafenib, has declined treatment with sorafenib, or does not have access to sorafenib.
Previously treated with sorafenib for greater than or equal to 4 weeks and discontinued sorafenib treatment at least 14 days prior to Day 1 due to either intolerance or radiographic progression
Prior systemic anticancer treatment for advanced HCC (except for sorafenib as described in the inclusion criteria)
Patients who have received prior treatment with sorafenib are eligible, as long as the sorafenib was not given in combination with cyclosphosphamide and/or topotecan. Patients with tumor relapse/progression while on sorafinib or having dose modifications or experiencing toxicity that required sorafenib to be discontinued are also ineligible to participate in this study.
Patients must be candidates for sorafenib
Previous treatment with sorafenib
Patients with known hypersensitivity to sorafenib or any other component of sorafenib.
Prior use of sorafenib
Contraindications to sorafenib
Known or suspected allergy or hypersensitivity to any component of TH-302, sorafenib, or any of the sorafenib excipients
Radioembolization within 8 weeks of day 1 dosing of sorafenib
PHASE I: Prior systemic therapy with sorafenib is allowed
PHASE II: Prior systemic therapy with sorafenib is allowed
Subjects must receive 1st dose of sorafenib 5-7 days prior to administration of SRS
Previously received mapatumumab or sorafenib.
Participants who have relapsed while on sorafenib therapy
Patients receiving sorafenib at the time of enrollment and those who are scheduled to receive sorafenib as part of a treatment plan are ineligible
No prior line of systemic therapy (includes participants who are sorafenib-naïve)
For patients who will receive enzalutamide monotherapy, failure or intolerance of prior sorafenib is required for enrollment; for patients who will receive combination therapy, prior sorafenib is excluded
Sorafenib was the only systemic therapy for HCC and was discontinued for disease progression or intolerance (Main Global and ME2 Cohorts only).
The participant received one prior systemic therapy regimen, excluding prior sorafenib, for the treatment of HCC (OLE Cohort only).
For Groups B or C patients must be off conventional therapy for at least 1 week prior to receiving treatment on this study
Patients should have been off conventional therapy for at least 1 week prior to receiving treatment on this study
Participants must be in first recurrence or have disease that is primarily refractory to conventional therapy
Conventional cytotoxic chemotherapy: ?4 weeks
no effective conventional therapy exists
Patients should have been off conventional therapy for at least 1 week prior to entry in this study; PD1/PDL1 inhibitors will be allowed if medically indicated
Ineligible for or have declined initial conventional combination chemotherapy
Patients must have disease that is no longer considered responsive to available conventional modalities or treatments (failed any known standard curative or effective therapy for that disease).
Has known metastatic disease as determined by conventional staging studies.
Conventional or stereotactic pituitary radiotherapy any time in the past
Subjects must have a histologically or cytologically proven advanced solid tumor malignancy for which palliative radiation is recommended. In solid tumors where pembrolizumab has been approved for use, patients may receive pembrolizumab as indicated, in the context of this protocol; in solid tumors where pembrolizumab has not been approved for use, the following criteria apply:\r\n* Patients must be resistant to at least 1 prior conventional chemotherapy regimen or other standard of care regimen,\r\n* Patient must have no remaining conventional treatment options proven to provide long-term disease control, and\r\n* Patient has declined other conventional treatment options\r\nPalliative radiation therapy may be recommended for primary tumor and/or any metastatic site that is accessible to biopsy
Patients who have been treated with any combination of surgical resection and neoadjuvant/adjuvant conventional chemoradiation therapy for resectable disease or conventional chemoradiation as definitive treatment for unresectable or borderline resectable disease are eligible for the study, provided that at least 180 days have elapsed since completing any previous radiation treatment; patients who have been receiving continued chemotherapy following their initial radiation treatment are eligible regardless of when the most recent chemotherapy was received; those patients who have received prior radiation therapy will constitute Cohort A and will receive SBRT as 5 Gy x 5
Prior conventional radiation to the same site is allowed as long as there is a greater than 3 months interval
Progressive hemato-lymphoid malignancy despite conventional therapy
Tumor must be potentially surgically resectable and curable with conventional surgery and radiation therapy
Subjects must have had histologic verification by a pathologist of cancer at original diagnosis; the tumor must be a non-CNS solid tumor; for subjects to be enrolled on the intratumoral arm, at least one lesion must be amenable to HSV1716 injection without undue risk, as determined by the interventional radiologist; disease must be considered refractory to conventional therapy or for which no conventional therapy exists
All diseases are advanced hematologic malignancies not curable by conventional chemotherapy; responses to conventional treatment range from zero to 30% but are typically short lived
Patients must have central nervous system (CNS)/ leptomeningeal disease which is refractory to conventional therapies or for which no conventional therapy exists OR recurrent brain tumors with a predilection for leptomeningeal dissemination (primitive neuroectodermal tumor [PNET], rhabdoid tumor)
Conventional chemotherapy or radiation within 4 weeks.
Conventional chemotherapy or radiation within 4 weeks.
Failed conventional therapy for their cancer or have a malignancy for which a conventional therapy does not exist
Subjects who are resistant to conventional chemotherapy or have declined conventional therapy for TNBC; patients having received any prior line of systemic therapy for inoperable/recurrent or metastatic disease are eligible
Suitable for conventional single agent chemotherapy
IDH1 gene-mutated solid tumors refractory to conventional therapy or the subject does not tolerate the conventional therapy
Conventional chemotherapy or radiation within 4 weeks.
Patients who are curable by conventional multidisciplinary management.
4 weeks (28 days) from any radiation treatment, stereotactic radiosurgery, conventional surgery, or chemotherapy
Intercurrent illness likely to prevent protocol therapy or conventional planned therapy
Patients must have CNS/ leptomeningeal disease including high risk medulloblastoma, or a CNS/leptomeningeal malignancy which is refractory to conventional therapies, or for which no conventional therapy exists, OR a recurrent brain tumors with a predilection for leptomeningeal dissemination (medulloblastoma, primitive neuroectodermal tumor [PNET], rhabdoid tumor)
Tumor must be surgically resectable and curable with conventional surgery
Lack of suitable conventional donor
Patients must have a histologically confirmed solid tumor that is considered incurable and is not amenable to conventional surgical, radiation therapy or chemotherapy treatment programs
Subjects who will need conventional therapy during the course of the study
Definitive findings of systemic metastasis on conventional imaging
Patients already scheduled to receive conventional radiotherapy, chemotherapy, biological therapy, vaccine therapy, or surgery as treatment (except at disease progression)
Able to undergo experimental imaging studies, as well as conventional bone and body imaging