Bevacizumab With or Without Anti-Endoglin Monoclonal Antibody TRC105 in Treating Patients With Recurrent Glioblastoma Multiforme

Status: Recruiting
Phase: Phase 1/Phase 2
Diagnosis: Brain/Neuro Cancer: Recurrent Glioblastoma
NCT ID: NCT01648348 (View complete trial on
DFCI Protocol ID: 12-538


This phase I/II trial studies the side effects and the best dose of TRC105 when giving together with bevacizumab and to see how well it works in treating patients with recurrent glioblastoma multiforme. Monoclonal antibodies, such as anti-endoglin monoclonal antibody TRC105 and bevacizumab, may stop the growth of tumor cells by blocking blood flow to the tumor. Giving TRC105 together with bevacizumab may be an effective treatment for glioblastoma multiforme.


Conducting Institutions:
Dana-Farber Cancer Institute, Brigham and Women's Hospital, Massachusetts General Hospital

Overall PI:
Lakshmi Nayak M.D., Dana Farber Cancer Institute

Site-responsible Investigators:
Andrew Chi, MD, PhD, Massachusetts General Hospital

Dana-Farber Cancer Institute: Lisa Doherty,
Massachusetts General Hospital: Cancer Trials Call Center, 877-789-6100

Eligibility Criteria

Inclusion Criteria: - Histological confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by preregistration central pathology review (Phase I) - Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review (Phase II) - Gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible - Evidence of tumor progression by MRI or computed tomography (CT) scan following radiation therapy or following the most recent anti-tumor therapy - Patients who have had surgical treatment at recurrence are eligible if they had a resection with measurable or non-measurable residual disease on postoperative imaging or if there is imaging evidence of disease progression as compared to the first postoperative scan - Measurable or evaluable disease by gadolinium MRI or contrast CT scan - Patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease - Blood and tissue samples for correlative research purposes required (Phase II) - Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2 - Absolute neutrophil count (ANC) ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - White blood cells (WBC) ≥ 3,000/mL - Hemoglobin ≥ 10.0 g/dL; Note: This level may be reached by transfusion - Total bilirubin ≤ institutional upper limit of normal (ULN) - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) ≤ 2 times ULN - Creatinine ≤ ULN - Life expectancy ≥ 12 weeks - Negative serum pregnancy test done ≤ 7 days prior to registration, for women of childbearing potential only - Urine protein creatinine (UPC) ratio < 1; Note: Urine protein must be screened by urine analysis for urine protein creatinine (UPC) ratio; for UPC ratio ≥ 1.0, 24-hour urine protein must be obtained and the level should be < 1,000 mg for registration - Calculated creatinine clearance must be ≥ 60 mL/min - Ability to provide informed written consent - Ability to complete questionnaire(s) by themselves or with assistance - Willing to return to enrolling institution for follow-up - Willing to provide mandatory blood and tissue samples for correlative research purposes (Phase II) - None of the following: - Pregnant women - Nursing women - Men or women of childbearing potential who are unwilling to employ adequate contraception throughout the duration of the study and for at least 6 months after treatment has ended - No prior hypersensitivity to Chinese hamster ovarycell products or other recombinant human antibodies - No prior hypersensitivity to triptan derivatives - No other active malignancy ≤ 3 years prior to registration; exceptions: nonmelanotic skin cancer or carcinoma-in-situ of the cervix; Note: If there is a history of prior malignancy, they must not be receiving other specific treatment (other than hormonal therapy) for their cancer - No uncontrolled infection - No immunocompromised patients or patients known to be human immunodeficiency virus (HIV) positive currently receiving combination antiretroviral therapy; Note: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial - No co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and adverse events of the prescribed regimens - No uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements - No history of hypertensive crisis or hypertensive encephalopathy - No clinically significant cardiovascular disease defined as follows: - Inadequately controlled hypertension (i.e., systolic blood pressure (SBP)> 160 mm Hg and/or diastolic blood pressure (DBP) > 90 mm Hg despite antihypertensive therapy) - History of cerebrovascular accident (CVA) within 6 months - Myocardial infarction or unstable angina within 6 months - New York Heart Association classification II, III, or IV cardiovascular disease - Serious and inadequately controlled cardiac arrhythmia - Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection) - Clinically significant peripheral vascular disease - No evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., Hereditary Hemorrhagic Telangiectasia type I [HHT-1]) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration - No serious or non-healing wound, active ulcer, or untreated bone fracture - No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months prior to registration - No significant vascular disease (i.e., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to registration - See Disease Characteristics - Fixed or decreasing dose of corticosteroids (or no corticosteroids) ≥ 7 days prior to registration - Any number of prior chemotherapy regimens for recurrent disease (Phase I) - No more than 1 chemotherapy or other non-antiangiogenic regimen for recurrent disease (Phase II) - Surgery ≥ 4 weeks prior to registration - Completion of radiation therapy ≥ 12 weeks prior to registration and prior chemotherapy ≥ 4 weeks prior to registration (≥ 6 weeks from nitrosourea-containing regimens) - Small molecular cell cycle inhibitors ≥ 2 weeks from registration - Willing to discontinue use of aspirin or medications that inhibit platelet function≥ 1 week prior to registration - Patients on full-dose anticoagulants are eligible provided the patient has been on a stable dose for at least 2 weeks of low molecular weight heparin or coumadin and has an international normalized ratio (INR) range of 2 to 3 - Aspirin doses > 325 mg daily are not allowed - No prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I) - No prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II) - Not receiving any other investigational agent that would be considered as a treatment for the primary neoplasm - No prior treatment with TRC105 - No invasive procedures defined as follows: - Major surgical procedure, open biopsy, or significant traumatic injury ≤28 days prior to registration - Anticipation of need for major surgical procedures during the study - Core biopsy ≤ 7 days prior to registration
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