Feasibility Phase: Patients must be < 21 years of age at the time of enrollment; please note: the feasibility phase is complete, effective with amendment #1
PHASE I: Patients must have biopsiable disease and be amenable to having two research biopsies
Platelets >= 100 x 10^9/L (for treatment phase)
Clinically significant cardiovascular disease, including:\r\n* Corrected QT (QTc) interval by Bazett’s formula > 480 ms (for treatment phase)\r\n* Symptomatic bradycardia < 45 beats per minute (for treatment phase)\r\n* Other clinically significant electrocardiogram (ECG) abnormalities (e.g. bundle branch block) may be eligible after discussion with the principal investigator (for treatment phase)\r\n* Clinically uncontrolled hypertension in the investigator’s opinion (for treatment phase)\r\n* The following within 6 months prior to cycle 1 day 1:\r\n** Congestive heart failure (New York Heart class III or IV) (for treatment phase)\r\n** Cardiomyopathy (for treatment phase)\r\n** Arrhythmia or conduction abnormality requiring medication; note: patients with atrial fibrillation/flutter adequately controlled by medication in the opinion of the treating physician and arrhythmias controlled by pacemakers are eligible (for treatment phase)\r\n** Severe / unstable angina, coronary artery/peripheral bypass graft, or myocardial infarction (for treatment phase)\r\n** Cerebrovascular accident or transient ischemia (for treatment phase)
Any serious, active infection at the time of treatment such as bacteremia (for treatment phase)
For Phase 1, only subjects HER2 or HER3 molecular/genetic alterations will be enrolled.
Phase 1: Subjects who have received prior alectinib therapy
Phase 2:
Allowable prior therapy\r\n* Phase 1: Progressed on standard of care therapy, if one is available\r\n* Phase 2: MPNST with 0-3 prior cytotoxic systemic therapies (no prior radiotherapy is necessary)
For phase 2 specifically, agree to pre- and on-treatment tumor biopsies
For the phase I cohort, subjects with one prior systemic treatment are eligible
PHASE I SUBJECTS ONLY: Patients must not have received prior navitoclax, unless the patient received < 7 days of navitoclax lead-in on this or another study and had to stop for reasons other than toxicity or disease progression; in the phase II portion of the study
PHASE I
Phase 1b:
Participant with bone-only disease (Phase 1 only). Note: Phase 2 participants may have predominantly lytic bone-only disease.
PHASE I ONLY:
The participant has adequate hematologic, organ, and coagulation function within 2 weeks (14 days) prior to enrollment (Phase 1b) or randomization (Phase 2).
PHASE I
No more than 1 prior chemotherapy regimen in the metastatic setting for the phase 2 portion; patients in the phase 1 portion could have received any number of prior lines of therapy
Prior fulvestrant for metastatic breast cancer will be allowed for phase 1 portion but not for the phase 2 portion
The inability to participate/complete phase 1 care due to:
Phase 1b:
FOR PHASE Ib PORTION OF THE STUDY:
Hemoglobin >= 8 g/dL (phase Ib) or >= 10 g/dL (for phase II portion)\r\n* For phase Ib portion only: patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; however, initial study drug treatment must not begin earlier than the day of the erythrocyte transfusion
FOR PHASE Ib ONLY:
Any other previous antitumor therapies for the current cancer event; this exclusion does not apply to phase Ib part of cohort 1
For the treatment phase: Patients with any histological subtype are eligible
Phase I: active dermatologic disease >= grade 3
Phase Ib (dose expansion
PHASE I:
No leukemic phase >5,000/µL circulating tumor cells.
PHASE I: Patients do not need to have measurable disease to enroll on phase I
For the phase 1b study, patients may have had the diagnosis of BOS for any period of time; for the phase 2 study, patients must be within 2 years from the time of diagnosis; patients may be at any time interval after SCT as long as the criteria for chronic GVHD and BOS are met
PHASE I: Any number of prior relapses
PHASE I: Has known gliomatous meningitis, subependymal spread, or extracranial disease
Life expectancy of ? 3 months (Phase Ia, Arm A) or ? 6 months (Phase Ia, Arm B and Phase Ib)
Prior RT to the same region within 12 months (Phase Ia, Arm A; subjects with tumors localized in the head and neck region or thorax) or at any time previously (Phase Ia, Arm B; treatment-naïve subjects with SCCHN and Phase Ib; treatment-naïve subjects with Stage III A/B NSCLC or SCCHN)
PHASE I:
For phase 1b: HER2 negative, as defined for phase II; any ER/PR (negative or positive) can be enrolled in the phase 1b portion
There is a high likelihood that the patient, in the opinion of the principal investigator (PI) or lead associate investigator (LAI), will meet the research phase eligibility criteria and proceed to transplant after induction phase therapy is completed
Phase Ib: 0 or 1
PHASE I (ARMS A, B, C, D, E, F, G, H, I, X, Y, Z)
For Phase I/Ib enrollment, patients with a CLIA confirmed EGFR mutation may be treatment naive; all other patients must have received at least one previous line of therapy; there will be no limits to prior lines of treatment for the Phase 1 portion
For the phase I portion of the study, patients may be included without a CCyR provided they remain in chronic or accelerated phase CML and have at least a CHR. For the Phase II portion of the study patients must be in complete cytogenetic remission (CCyR), regardless of the stage of disease they had at the time they started therapy with TKI.
For the phase I portion of the study, patients in blast phase. For the phase II portion of the study, patients in accelerated or blast phase.
Phase Ib: no restriction on prior therapy
History of symptomatic Clostridium difficile infection within 1 month prior to dosing Additional phase specific exclusion criteria: Phase Ib Dose Escalation Arm A (Venetoclax and Cobimetinib)
For Part C (Phase 2): recurrent ALL patients with CNS 3 status are not eligible
PHASE I:
Phase 2 expansion: NSCLC
Phase 2 expansion: Melanoma
Phase 2 expansion: Transitional cell carcinoma of the GU tract
Phase 2 expansion: SCCHN
Phase 2 expansion: TNBC
Phase 2 expansion: Gastric Cancer
Patients will be excluded from the Induction Phase and the Maintenance Phase if administration of their chemotherapy would be inconsistent with the current local labelling (SmPC) (e.g., in regard to contraindications, warnings/precautions or special provisions) for that chemotherapy. Investigators should check updated labelling via relevant websites at the time of entry into the Induction Phase and the Maintenance Phase
Phase 1 and 2 (except Phase 2 subjects with known lymphoma) >=1500 cells/mm3
Phase 1 and 2 (except Phase 2 subject with known lymphoma) >=100,000 cells/mm3
Prior treatment with a VEGFR TKI (including pazopanib) (Phase 2 only)
adult Phase 1 Part A and Phase 2: ?16 years old at the time of screening
Be eligible for commercial receipt of therapy to be used in this study in combination with RTA 408 (i.e., ipilimumab or nivolumab in the Phase 1b portion and nivolumab only in the Phase 2 portion);
Have received prior treatment with therapy to be used in this study in combination with RTA 408 (i.e., ipilimumab or nivolumab) if enrolling in the Phase 2 portion of the study. This criterion does not apply to patients enrolling in the Phase 1b portion of the study.
Patients planning to enroll in the phase I portion of this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation\r\n* NOTE: Phase I is closed to accrual effective 4/1/15
KEY INCLUSION CRITERIA\n\n          -  Histological confirmation of classical Hodgkin's Lymphoma (cHL) with relapsed or\n             refractory disease who, for the lead-in phase, either have had a prior autologous or\n             allogeneic HSCT or are not eligible for HSCT, and , for the expansion phase, have had\n             a prior allogeneic HSCT. In the expansion phase there must be a documented CD3+ donor\n             chimerism of ?20%.\n\n          -  Patients must be off previous cHL therapy for at least 28 days prior to randomization\n             in the lead-in phase/first dose of study treatment in the expansion phase.\n\n          -  At least 1 fluorodeoxyglucose (FDG) PET avid (Deauville 4/5) measurable lesion >1.5 cm\n             on PET-CT scan as defined by the Response Criteria for Malignant Lymphoma (for the\n             lead-in phase) and the Lugano Classification (for the expansion phase) that has not\n             previously been irradiated.\n\n          -  Expansion phase: Required \de novo\ or \archival\ tumor biopsy, as well as required on\n             treatment biopsy\n\n          -  Estern Cooperative Oncology Group (ECOG) Performance Status 0 or 1\n\n        KEY EXCLUSION CRITERIA\n\n          -  Patients with prior allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT) who\n             have had:\n\n               1. Lead-in phase: allo HSCT performed <12 months prior to randomization. Expansion\n                  phase: allo-HSCT performed ?4 months prior to the first dose of study treatment.\n                  NOTE: Patients who have had allo-HSCT performed >4 months prior to the first dose\n                  of study treatment must have discontinued all immunosuppressive therapy, and must\n                  have no clinical evidence of GVHD; or\n\n               2. Immunosuppressive treatment for acute or chronic GVHD within 3 months prior to\n                  randomization for the lead-in phase or prior to the first dose of study treatment\n                  for the expansion phase (with the exception of those patients who required 15\n                  mg/day oral prednisone or equivalent). Patients who required 15 mg/day oral\n                  prednisone or equivalent must have discontinued it within 7 days prior to first\n                  dose of study treatment; or\n\n               3. Acute Grade 3 or Grade 4 GVHD at any time in the past (as defined by the modified\n                  Seattle Glucksberg criteria (Consensus Conference on Acute GVHD Grading\n                  Criteria); or\n\n               4. Prior chronic GVHD (as defined by the NIH Consensus Development Project) that\n                  persisted for >6 months and required systemic immunosuppression (with the\n                  exception of those patients who required 15 mg/day oral prednisone or\n                  equivalent). Patients who required 15 mg/day oral prednisone or equivalent must\n                  have discontinued it within 7 days prior to the first dose of study treatment; or\n\n               5. A donor lymphocyte infusion (DLI) within 3 months prior to randomization for the\n                  lead-in phase or first dose of study treatment for the expansion phase.\n\n          -  Prior therapy with an anti PD 1 or anti PD L1 mAb.\n\n               1. Lead-in Phase: May be enrolled if patient stopped prior anti PD1 or anti-PD-L1\n                  therapy more than one year prior to randomization and had a documented prior\n                  response.\n\n               2. Expansion Phase: Prior therapy with an anti-PD-1 or anti-PD-L1 agent following\n                  allo-HSCT is prohibited unless the therapy was stopped more than one year prior\n                  to the first dose of study treatment, and the patient had a documented prior\n                  response. NOTE: Prior therapy with an anti-PD-1 or anti-PD-L1 agent prior to\n                  allo-HSCT is permitted with no time limits and irrespective of a documented\n                  response.\n\n               3. Patients with a history of ?Grade 3 anti-PD-1 or anti-PD-L1-related immune\n                  toxicity are not eligible.
For dose escalation phase (Phase Ib) distant metastatic disease or unresectable disease and not a candidate for down staging to resection.
Any comorbid condition that confounds the ability to interpret data from the study as judged by the Investigator or Medical Monitor. BEV-Specific Concerns (Note: These exclusion criteria apply to the Phase 2 portion of the study even though BEV is not administered so that the patient populations between Phase 1 and Phase 2 are similar):
Any number of prior treatment regimens (in the phase I portion only); prior erlotinib is allowed in the dose finding phase and expansion cohort A; (only EGFR mutated patients are eligible)
Patients who currently are participating in other phase III therapeutic clinical trials and/or who have participated in other phase III therapeutic clinical trials in the previous 30 days
SECOND COURSE PHASE (RETREATMENT PERIOD FOR POST-COMPLETE RESPONSE RELAPSE ONLY)
For Phase 1A: no specific restriction
Phase Ib:
For patients who will be entering the “expansion phase” of the trial, the patient must be able to safely delay radiation by at least 6 weeks
Phase II patients with sarcomatoid subtype MPM or Phase III patients with biphasic or sarcomatoid subtype MPM
Phase 2:
FOR EXPANSION PHASE ONLY: For the expansion phase, patients must have measurable disease accessible for biopsy
FOR EXPANSION PHASE ONLY: For the expansion phase, patients must have archival specimens from the time of primary or recurrence diagnosis
PHASE I: Filgrastim (GCSF) is not allowed during screening or during the first cycle for phase I patients
Patients agreeing to the optional biomarker study in the expansion phase only need to have an accessible primary tumor; (optional biomarker studies will be done in up to 18 patients in the expansion phase only)
PHASE I: Patients may not have received > 2 prior chemotherapies for advanced disease
Phase 2 Arms 1-3: Suitable to receive a 6-week course of BCG in the adjuvant setting within 6 weeks following TURBT. Phase 2 Arm 4: Suitable for monotherapy vaccine administration post-TURBT. For Phase 1 only: Has previously received 3-6 weekly doses of BCG.
PHASE I
Intermediate-2 and higher by International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) post polycythemia vera (PV)/essential thrombocythemia (ET) MF and primary myelofibrosis (PMF) patients either in\r\n* Chronic phase (MF-chronic phase [CP])\r\n* Accelerated phase (MF-accelerated phase [AP])
For Phase 2 individuals either:
Phase 1b Subjects only:
For Phase 2 of the study, has a diagnosis of mixed squamous and nonsquamous (or adenosquamous) NSLC.
For Phase 2 of the study:
For Phase l, no more than 3 prior anticancer regimens (IL-2 or interferon do not count towards the total).
Patients who have failed nilotinib, including those who are refractory to nilotinib at any dose or have relapsed on nilotinib at any dose will be eligible for the study; patients currently on nilotinib will continue on their prescribed dose of nilotinib and MEK-162 will be added based on the current cohort level in phase I or at the established MTD in phase II; in the instance the nilotinib dose is greater than the current cohort (in phase 1) or the MTD (in phase 2) patients will be dose reduced to the dosage as prescribed by protocol and then dose escalated as allowed in protocol at the principal investigator's (PIs) discretion
Subjects in the Phase 1b portion and in Group 1 and Group 3 of the Phase 2a portion may have received any number of prior therapies for breast cancer. Subjects in Group 2 of the Phase 2a portion may have received up to 3 lines of therapy in the metastatic setting (not including adjuvant or neoadjuvant therapy)
Patients must be considered good candidates for a phase 1 trial and the treating physician must intend to enroll the patient on a phase 1 clinical protocol, if possible; patients are not required to have progressed on their last line of therapy prior to enrollment\r\n* Other clinical trials are also acceptable; for example, an applicable phase 2 or phase 3 trial may exist for which the patient would be eligible and for which available information (inclusive of next generation sequencing [NGS]) would be relevant to such enrollment; regardless, the pertinent point is that it is the intent of the physician to use NGS data, to the degree possible, to select appropriate therapy, when selecting patients for this trial
Relapsed or relapse/refractory MM with at least 1 prior line of therapy for phase 1 and 1 to 5 prior lines of therapy for phase 2.
Bortezomib refractory patients are not permitted on the Phase 2 part of the study.
Patient willingness to undergo tumor biopsy at baseline and on treatment (optional for Phase 1; mandatory for Phase 2)
Subject has been treated in the OXiGENE-sponsored Phase 2 study OX4218s
For Phase 2 only: MET+ status
Whole brain or focal radiation therapy within 14 days prior to Cycle 1 Day 1 (C1D1) for Phase 1b or prior to randomization for Phase 2
Eligibility for phase 1 and phase 2 components:\r\n* Phase 1 – clinical T3 or T4 or N1 or M1 cancer which is untreated or previously treated with platinum based therapy with primary tumor still present in the bladder and amenable to sampling before and after treatment, as indicated\r\n* Phase 2 – clinical T2-4 N0 or N1 untreated with primary tumor still present in the bladder and amenable to sampling before and after treatment, as indicated
Prior enrollment in the OncoGenex Phase 2 Study OGX-427-02.
Prior temozolomide is not required for the phase 1 component; prior radiation is required for the phase 1 arm.
Patients on the phase 2 portion of the study may not have more than 2 prior regimens for recurrent disease for glioblastoma/gliosarcoma. Patients on the phase 1 portion of the study may not have had more than 3 prior regimens.
PHASE I PATIENTS:
Patients must be >= 2 weeks since any investigational agent administered as part of a phase 0 study (also referred to as an “early phase I study” or “pre-phase I study” where a sub-therapeutic dose of drug is administered) at the coordinating center PI’s discretion, and should have recovered to eligibility levels from any toxicities
Prior treatment with immune checkpoint inhibitors, immunomodulatory monoclonal antibody (mAbs), and/or mAb-derived therapies is allowed provided that at least 6 weeks (Phase 1a) or 3 weeks (Phase 1b) have elapsed between the last dose and the proposed Cycle 1, Day 1, with the exceptions as specified in protocol Dose-Exploration/Expansion Cohorts in Phase 1b:
Life expectancy of > 3 months for the run in phase and > 6 months for the randomized phase
Corticosteroids initiated at the time of tumor diagnosis or recurrence for treatment of nerve compression or other symptoms is permitted during this phase of the trial, but will not be permitted during the immunotherapy phase, with the exception of a self-limited course of steroids
Participation in a Phase I lapatinib trial that has met its study objectives.
Enrollment in a Phase I trial
PHASE I: Any diagnosis of cancer prior to age 21
PHASE I: Off treatment
PHASE I: Pregnant (per patient report)
Phase 1-Diagnosis of advanced or metastatic solid tumor; Phase 2-Diagnosis of NSCLC
PHASE 0: Ability to stand and walk unassisted
PHASE 1 & 2: Ability to stand and walk unassisted
PHASE 0: Not yet had surgery
PHASE 1 & 2: Identified within two weeks of surgery
Phase I: From 3–36 months post-surgical treatment
PHASE 1: PARENT ELIGIBILITY: Patient is at least 1.5 years from treatment
PHASE 2: PEER MENTOR ELIGIBILITY: Age 21-29
PHASE 2: PEER MENTOR ELIGIBILITY: At least 1.5 years from treatment
PHASE 2: PATIENT ELIGIBILITY: Age 18-25
PHASE 2: PATIENT ELIGIBILITY: At least 1.5 years from treatment
PHASE 3A: AYA SURVIVOR ELIGIBILITY: Age 18-29
PHASE 3B: PEER MENTOR ELIGIBILITY: Age 21-29
PHASE 3B: PEER MENTOR ELIGIBILITY: At least 2 years from treatment
PHASE 3B: PATIENT ELIGIBILITY: Age 18-25
PATIENTS AND PARTNERS: Prior enrollment in a couple-based mind-body intervention research study (protocols 2011-1179, 2013-0496, 2014-0036) conducted by the principal investigator including phase 1 or phase 2 of the current study
Treatment cannot begin prior to re-registering to the crossover phase and will ideally begin =< 7 days after registration for the crossover phase
PHASE 1 (DEVELOPMENT OF NARRATIVE MESSAGES)
PHASE 2 (RANDOMIZED CONTROLLED TRIAL [RCT] GROUP)
Phase 2: In Phase 2, clinician participants will be the oncology clinician of record (i.e., oncologist, nurse practitioner) of the first five patients enrolled in the intervention group of the randomized trial
Phase 2: The same four groups of stakeholders from Phase 1 will become involved as research collaborators/consultants for Phase 2 of the study and will not be considered study participants (i.e., will not be registered with Quality Assurance Office for Clinical Trials [QACT])
MONITORING PHASE:
Monitoring phase:
RANDOMIZATION PHASE:
Randomization phase:
At least 3 months into the maintenance phase, with at least 6 months left of\n             maintenance therapy
EVALUATION PHASE
Participants must not be eligible only for phase I trial
Phase I: Self-identify as Hispanic/Latino
PHASE I: MGUH patients presenting for well visits, and patients' parents
Women who are premenopausal, are on a stable contraceptive regimen, and are planning to continue the same regimen through surgery are eligible to participate; for women who are on hormonal contraception regimens that have a placebo phase, the following should be recorded regarding the day of baseline core biopsy and the day of surgery: the agent, whether they are in active or placebo phase, the day of the phase (e.g. day 13 of 21-day active phase or day 4 of 7-day placebo phase); this information will have to be back-calculated for the day of core biopsy, but best attempt should be made
RPFNA performed within 6 months of the study entry visit and in the follicular portion (day 1-10) of the menstrual cycle; note that day 1 is defined as the first day of bleeding; for non-menstruating women, RPFNA during the follicular phase must be confirmed by hormone levels drawn on the day of RPFNA; either clinical laboratory results are sent to protocol chair for assessment of menstrual cycle phase; or an additional frozen serum aliquot is sent to University of Kansas Medical Center (KUMC) for assay of hormone levels and phase confirmation; confirmation of follicular phase will be included in the eligibility report for the potential subject
Attend classes at either Houston Community College (HCC) Central Campus or Coleman Campus (Phase 1 and Phase 2) or Spring Branch Campus (Phase 2)
Own a smartphone capable of receiving texts from the study's text messaging resource (Phase 1 and Phase 2)
Use phone text-messaging features on a regular basis (Phase 1 and Phase 2)
Provide cell phone number (Phase 1 and Phase 2)
Phase I:
Phase Ib dose expansions Arms 1, 2 and 3
Patient scheduled for CT that includes the abdomen with a multiphasic contrast enhanced protocol (e.g. triple phase or quadruple phase liver CT)
Eligible for the trial UPCC #01615, “A Phase Ib Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects with Resectable Advanced Melanoma\
Ineligible for the trial UPCC #01615, “A Phase Ib Tissue Collection Study of Pembrolizumab (MK-3475) in Subjects with Resectable Advanced Melanoma\
PHASE I:
PHASE I: Women who do not have capacity to participate
Be a phase 1 trial in expansion, phase 2, or 3
PHASE I: Pregnant women will be eligible to participate
USABILITY PHASE: Pregnant women will be eligible to participate
Are eligible to participate in one of the phase III or IV BCCT open at the CTRC at the time of diagnosis