For patients to be treated with a regimen containing bevacizumab:
Patients with prior treatment with bevacizumab (or any other anti vascular therapy, e.g., cediranib) for platinum resistant recurrence; (Note: prior bevacizumab in initial therapy and/or platinum sensitive recurrent setting is allowed)
Prior bevacizumab therapy is excluded.
Patients who have received prior therapy with bevacizumab, or related drugs (previous therapy with carboplatin is allowed)
Has received trebananib or another angiopoietin-2 directed therapy (prior treatment with bevacizumab is not an exclusion criteria)
Patients must not have received prior anti-VEGF therapy including bevacizumab (i.e. patients must be bevacizumab naive)
Prior bevacizumab
Patients who have had previous treatment with bevacizumab
There is no limit on the number of prior relapses but the most recent relapse must be the first relapse on a bevacizumab-containing regimen
Patients who have received investigational or licensed drugs that target vascular endothelial growth factor [VEGF] or VEGF receptors/pathways (such as bevacizumab, sorafenib, pazopanib, sunitinib, axitinib, cabozantinib, etc.) for the treatment of recurrent cancer are not eligible; exceptions: prior treatment with bevacizumab in the up-front or maintenance setting is allowed, provided the patient had a favorable response to bevacizumab; favorable response is defined as having had a disease free interval of > 6 months following completion of a bevacizumab-containing regimen; if questions, contact the principal investigator (PI)
Patients must have been previously treated with radiation therapy and temozolomide (bevacizumab-naive – groups 1 and 3) or radiation therapy, temozolomide and bevacizumab (bevacizumab-exposed – groups 2 and 4); therapy with these agents may be given together or sequentially in the past
Patients must be considered bevacizumab-resistant, i.e.; have a treatment-free interval following a response to bevacizumab (complete response [CR], partial response [PR], or stable disease [SD]) of less than 6 months, or have progressed during treatment with a bevacizumab-containing therapy
If participant was treated with bevacizumab, at least 4 weeks must elapse before treatment with either agent (cyclophosphamide or rQNestin34.5v.2)
For biopsy cohort, participants must be bevacizumab naive or received the last bevacizumab treatment at least 12 months prior to Cycle 1 Day 1 and according to the investigator's judgment the planned biopsies would not expose participants to substantially increased risk of complications
Patients may have had previous systemic treatment regimens (no limit to number of prior therapies); patients with prior treatment with bevacizumab are eligible for enrollment into the study; NOTE: except for bevacizumab, a 28 day wash-out period prior to registration is mandatory for all systemic treatments
Prior use of bevacizumab
Patients may not have had prior bevacizumab, based on case reports of tracheoesophageal fistula in patients treated with bevacizumab and radiotherapy
Patients who have had any prior bevacizumab, due to case reports suggesting a possible risk of severe toxicity in combination with radiotherapy
Prior treatment with any anti-angiogenic agent (including bevacizumab)
Patients may have received previous NY-ESO-1 vaccine therapy; patients who received maintenance paclitaxel or bevacizumab are eligible for enrollment provided they have discontinued therapy (at least 4 weeks for prior taxane or prior bevacizumab) prior to randomization and recovered from toxicities to less than grade 2
Only patients for whom their neuro-oncologist has planned to give bevacizumab and temozolomide 50mg/m^2/day as part of their treatment are eligible for this study
Patients who have had previous treatment with bevacizumab and/ or NovoTTF 100A system
Patients with advanced adenocarcinoma of the colon or rectum not curable with surgery or radiotherapy and have been previously treated for their disease with FOLFIRI plus bevacizumab in the first line metastatic setting; patients will only be eligible if their last line of therapy prior to enrolling onto the study was FOLFIRI and bevacizumab received no more than 6 months prior to enrolling in this study; they should have been treated with FOLFIRI plus bevacizumab until disease progression is radiographically documented
Bevacizumab within the last 3 weeks before enrollment on trial
Bevacizumab naive
(Bevacizumab-related exclusion) Known hypersensitivity to any component of bevacizumab
Patients must not have received prior treatment with bevacizumab.
Be at least 14 days from the last administration of bevacizumab
Has previously received treatment with bevacizumab
Patients with prior bevacizumab use for tumor treatment; patients who received bevacizumab for symptom management, including but not limited to cerebral edema, pseudoprogression can be included in the study
Have adequately recovered from second look surgery to be able to start bevacizumab within 7 weeks of this procedure
Participant may have received bevacizumab (or other antiangiogenic agent) and/or cyclophosphamide in the past
Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab
Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 4 weeks
Patients may have received prior targeted therapy such as bevacizumab
Bevacizumab® or other anti-angiogenic therapy.
Prior therapy with bevacizumab
Subjects must not have received capecitabine or bevacizumab for this disease
Unequivocal evidence of tumor progression during prior bevacizumab treatment per RANO criteria.
Has been treated previously with bevacizumab
Patients previously treated with bevacizumab.
COHORT II: Prior progression on a bevacizumab-containing regimen (defined as having progressed/grown through bevacizumab by RANO criteria within 2 months of prior bevacizumab treatment)
Bevacizumab-naive – no prior exposure to bevacizumab
Patients who have received previous anti-angiogenic treatment (experimental or marketed: bevacizumab, thalidomide, CP-547632, sunitinib, sorafenib or others)
Patients with an impending fracture who have had bevacizumab are eligible provided there will be a 3-week window between their last infusion and surgery
Prior therapy with bevacizumab, liposomal doxorubicin, or everolimus
Prior treatment with bevacizumab within 12 weeks of study entry
Treated with antiangiogenic agents (like bevacizumab) within 4 weeks before biopsy
Patients receiving bevacizumab within 12 weeks prior to protocol treatment
Prior treatment with bevacizumab
Current or recent (within 10 days prior to first dose of bevacizumab) use of aspirin (> 325 mg/day)
No more than 2 prior chemotherapies and 1 relapse; prior bevacizumab therapy is allowed
Patients may not have previously been treated with bevacizumab or lapatinib
Patients treated with any systemic anti-cancer therapy for NSCLC within 21 days prior to randomization (6 weeks for Bevacizumab).
Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids.
Patients who have undergone prior resection, radiation therapy, and/or chemotherapy (except bevacizumab)
Minor surgery, including insertion of an indwelling catheter, within 24 hours prior to the first bevacizumab infusion
Patients who have received bevacizumab, Gliadel, or are on active therapy with Optune are not eligible
Known hypersensitivity to inactive ingredient of bevacizumab
Prior exposure to another anti-angiogenic therapy (eg, bevacizumab, sunitinib)
Arm 1 patients must have not received bevacizumab previously
Arm 2 patients must have progressed/recurred on bevacizumab as the most recent regimen; patients on arm 2 should continue on bevacizumab as clinically necessary to control brain edema
Patients who have been off bevacizumab for < 30 days prior to baseline MRI
Patient is to receive bevacizumab as maintenance treatment
No prior therapy with drugs other than oxaliplatin and a fluoropyrimidine plus bevacizumab for this disease; chemotherapy drugs and bevacizumab may be stopped and started as long as no prior disease progression requiring change in chemotherapy agents occurred
Patients for whom, in the opinion of the Investigator, there is clinical benefit to administer bevacizumab as a first-line treatment and for whom bevacizumab is approved and available in this setting.
Have received more than one prior antiangiogenic agent (that is, bevacizumab, sorafenib, sunitinib) for TCC of the urothelium.
Patients who will be enrolled under protocol amendment # 2 must have previously received bevacizumab, either discontinued due to intolerability, or progressed after at least 2 cycles of bevacizumab
Continued treatment with bevacizumab with documented evidence of disease progression on a bevacizumab-containing regimen
At least 21 days since the last dose of bevacizumab, other antibody, or interferon.
Bevacizumab will be allowed if given for symptomatic control of vasogenic edema and to avoid high dose of corticosteroids
An interval of >= 4 weeks after the last administration of any investigational agent or prior cytotoxic therapy (except bevacizumab); there should be 14 days interval between the last dose of bevacizumab and first day of treatment on study
Prior treatment with bevacizumab within twelve weeks before the first infusion.
Prior receipt of antiangiogenic treatment, including but not limited to bevacizumab, is optional. If used, it can be used in the first line or recurrent setting.
Patient has previously received standard of care chemo-radiation with temozolomide, ± adjuvant temozolomide and bevacizumab and now has radiographic evidence of recurrent/progressive GBM or GS during or after bevacizumab.
Participants who have received prior bevacizumab are eligible unless there is evidence of unacceptable toxicity due to prior bevacizumab exposure
Capecitabine and bevacizumab considered appropriate treatment for the patient
Intolerance to bevacizumab defined as any NCI CTCAE grade 3 or grade 4 toxicity attributed to this agent that required discontinuation of bevacizumab (e.g., arterial thromboembolism [ATE], perforation, wound healing difficulty, proteinuria, reversible posterior leukoencephalopathy syndrome [RPLS]); Note: patients with prior grade 3 bevacizumab-related hypertension may be permitted if hypertension was manageable with standard oral antihypertensives as so judged by the treating physician
Previous therapy with bevacizumab is allowed, but patient who experienced serious dose-limiting toxicities while on prior bevacizumab therapy are excluded
Progression following both standard combined modality treatment with radiation and temozolomide chemotherapy, as well as bevacizumab
Has been treated previously with bevacizumab
Treatment with bevacizumab in at least one prior line of therapy for metastatic disease
Advanced unresectable, metastatic or recurrent colorectal carcinoma (CRC) for which treatment with FOLFOX6 with or without bevacizumab, FOLFIRI with or without bevacizumab, CAPOX, or regorafenib would be acceptable as determined by the Investigator. FOLFIRI-refractory patients with CRC enrolling on the FOLFIRI study arm must have failed treatment with one FOLFIRI with or without bevacizumab regimen for unresectable or metastatic disease. Treatment failure is defined as progression of disease (clinical or radiologic) during treatment with FOLFIRI with or without bevacizumab or < 3 months after the last dose of treatment with FOLFIRI with or without bevacizumab. Patients with CRC enrolling on the regorafenib arm of this study will have previously received at least two previous lines of therapy for advanced colorectal cancer, and will have previously received treatment with a fluoropyrimidine, oxaliplatin, and irinotecan. Patients with K-ras wild type tumors enrolling on the regorafenib arm will also have previously received either cetuximab or panitumumab.
For patients to be treated with a regimen containing bevacizumab:
Patients who have received previous treatment with bevacizumab for CNS disease are not eligible for participation
Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab
Prior treatment with doxorubicin and/or bevacizumab
Patients who have had prior anti-angiogenic therapy, including but not limited to sorafenib, brivanib, bevacizumab, or sunitinib
Prior treatment with bevacizumab
FOR COHORT 1: (BEVACIZUMAB ELIGIBLE)
FOR COHORT 2 (BEVACIZUMAB INELIGIBLE):
Treatment with trastuzumab, bevacizumab or other targeted therapies within the past 2 weeks
BEVACIZUMAB-SPECIFIC EXCLUSIONS:
BEVACIZUMAB-SPECIFIC EXCLUSIONS
Patients must have been previously treated with radiation therapy and temozolomide (bevacizumab-naive - groups 1 and 3) or radiation therapy, temozolomide and bevacizumab (bevacizumab-exposed -groups 2 and 4); therapy with these agents may be given together or sequentially in the past
For bevacizumab-naive patients (groups 1 and 3) a minimum of 6 months must have elapsed since completion of radiation therapy for study entry, and there is no minimum time since completion of last chemotherapy; for bevacizumab-exposed patients (groups 2 and 4) no minimum time since completion of last radiation therapy, biologic agents, or chemotherapy will be required for study entry
Prior use of pazopanib or other agents targeting angiogenesis pathway (such as bevacizumab, sunitinib, or sorafenib) in the metastatic setting
Prior disease progression/recurrence during or immediately following treatment with bevacizumab; any questions should be directed to the PI
Patients who have had prior chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C); patients must be off treatment with temozolomide for at least 23 days; patients who received non-cytotoxic drug therapy must be off treatment for at least 2 weeks; for patients enrolling in Part 1 or Part 3 AND who have progressed on a prior bevacizumab-containing regimen, patients may continue treatment with bevacizumab 10 mg/kg monotherapy, with last dose of bevacizumab administered no fewer than 14 days from start of plerixafor and bevacizumab; for participants enrolling in Part 1 or Part 3 AND who have progressed on a prior anti-VEGF(R) (other than bevacizumab) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days before receiving plerixafor and bevacizumab; for patients enrolled in Part 2 (surgical substudy) AND who have progressed on a prior bevacizumab or other anti-VEGF(R) containing regimen, patients must be off anti-VEGF(R) treatment for at least 28 days prior to surgery; NOTE: participants must have recovered to a grade 0 or 1 from the toxic effects of prior therapy (with the exception of lymphopenia, which is common after therapy with temozolomide); for any patient who received prior bevacizumab or an anti-VEGF(R) therapy, patient must NOT have discontinued that treatment regimen due to a treatment-related toxicity
Patients must be at least 48 hours from placement of central catheter before receiving first dose of bevacizumab
Patients must be willing to forego other drug therapy against the tumor while being treated with bevacizumab and temozolomide
Subjects who have progressed on Bevacizumab treatment
(continued from no. 22) Subjects will be apprised of the large potential risk to a developing fetus. It is not known whether bevacizumab is excreted in human milk. Because many drugs are excreted in human milk, bevacizumab should not be administered to nursing women. Patients of childbearing potential must agree to use contraceptive measures during study therapy and for at least six months after completion of bevacizumab therapy.
Previous bevacizumab within 6 weeks prior to enrollment
Prior treatment with bevacizumab is not allowed.
1st progression of GBM on bevacizumab-containing regimen or within 8 weeks of discontinuing bevacizumab. In either case, must have received a minimum of 8 weeks (4 infusions) of bevacizumab.
14 days from last dose of bevacizumab
Known hypersensitivity to any inactive ingredient of bevacizumab
Prior chemotherapy for recurrent glioblastoma with nitrosourea compounds or bevacizumab
Bevacizumab will be allowed for patients with non-squamous carcinoma. Prescribing information must be followed and precautions have to be taken into consideration (e.g., patients having presented a serious hemorrhage or recent hemoptysis should not receive bevacizumab).
Patients who are taking bevacizumab or have taken bevacizumab within the past 2 weeks for treatment of their brain metastases
Bevacizumab within 4 weeks.
Patients who have previously discontinued bevacizumab-containing regimes due to drug-related toxicity.
Prior treatment with bevacizumab within twelve weeks before the first infusion.
For those receiving bevacizumab, standard medical exclusionary conditions apply
Participants with newly detected enhancement are eligible, with bevacizumab treatment hoped to prevent symptoms
- bevacizumab or aflibercept
Prior treatment with bevacizumab or an experimental anti-angiogenic agent.
Prior therapy with bevacizumab or other VEGF pathway targeted therapy in the recurrent setting; bevacizumab in the upfront setting is allowed
Bevacizumab-refractory patients: these patients may not have more than 2 prior relapses not counting the current relapse being treated by this protocol and must have received multiple chemotherapy regimens, including a temozolomide regimen and a bevacizumab regimen
Planned to receive bevacizumab
The last dose administered of bevacizumab must be at least 21-days but not more than 56-days from enrollment
Last dose of bevacizumab >= 2 weeks prior to registration (Phase I); note: for the phase II study only, prior exposure to bevacizumab is not allowed
Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I)
Patients enrolling onto Cohort 2b who have been taken off bevacizumab must have had at least a 28 day washout from any previous administration of bevacizumab. It is preferred that patients who fail bevacizumab prior to trial entry remain on bevacizumab in the trial.
Received prior bevacizumab therapy or had clinically documented reason why not administered
Medical conditions that would contraindicate bevacizumab therapy in non-squamous NSCLC (Arms C, D, E, and F)
Subjects receiving bevacizumab for maintenance therapy are excluded (subjects who received bevacizumab as part of their adjuvant therapy will be permitted)
Has received bevacizumab within 4 weeks prior to randomization
No bevacizumab =< 3 months of study registration
Failure on bevacizumab (either as a monotherapy or a combination) as most recent regimen confirmed by tumor recurrence on MRI.
The patient must have failed no more than one regimen of bevacizumab.
There must be a minimum of 14 days (i.e., an interval equal to or greater than 14 days) since last treatment with bevacizumab and registration
Prior allergic reaction to bevacizumab or severe adverse event with bevacizumab.
Prior therapy with bevacizumab
BEVACIZUMAB-SPECIFIC EXCLUSIONS
Known allergies to oxaliplatin (or other platinum agents), leucovorin, 5-FU, nab-paclitaxel (or other taxanes) or gemcitabine Exclusion Criteria Specific to Bevacizumab-Containign Arms (Arms A, B, and F) (Patients who meet any of the following criteria will be excluded from enrollment into bevacizumab-containing Arms A, B, and F:)
Anti-angiogenic agents including bevacizumab: 4 weeks
Progression of disease assessed by local site using Revised Assessment in Neuro-Oncology (RANO) criteria, with plan to administer bevacizumab, either as single therapy or in conjunction with other chemotherapeutic regimens, in order to treat tumor progression/recurrence per the treating physician; patients receiving bevacizumab primarily for reduction of edema (i.e. alleviation of symptoms) rather than for tumor treatment are excluded
Patients who have not previously received a bevacizumab-containing regimen (i.e., this must be the first bevacizumab-containing therapy administered to the patient)
Patient must be scheduled to receive treatment with a bevacizumab containing chemotherapy regimen; patient can be treated with bevacizumab alone or in combination with other chemotherapies; patient may also be receiving treatment with Optune
For cohort A, only patients for whom their neuro-oncologist has planned to give bevacizumab with lomustine are eligible for this study
For cohort B, only patients for whom their neuro-oncologist has planned to give bevacizumab monotherapy are eligible for this study
Platelets >= 75,000/mcL for bevacizumab monotherapy cohort; > 100,000/mcL for bevacizumab + lomustine cohort