Bevacizumab with or without Anti-Endoglin Monoclonal Antibody TRC105 in Treating Patients with Recurrent Glioblastoma Multiforme

  • Study type:

    Interventional What is this?

    Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • Study phase:

    I/II What is this?

    During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

Study IDs

  • Site IRB:

    • Scottsdale/Phoenix, Arizona: 12-000818
    • Jacksonville, Florida: 12-000818
    • Rochester, Minnesota: 12-000818
  • NCT ID:

    NCT01648348
  • Sponsor Protocol Number:

    N1174

About this study

This partially randomized phase I/II trial studies the side effects and the best dose of anti-endoglin monoclonal antibody TRC105 when given together with bevacizumab and to see how well they work in treating patients with glioblastoma multiforme that has come back. Monoclonal antibodies, such as anti-endoglin monoclonal antibody TRC105 and bevacizumab, may find tumor cells and help kill them. Giving anti-endoglin monoclonal antibody TRC105 together with bevacizumab may be an effective treatment for glioblastoma multiforme.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Histological confirmation of grade 3 or 4 glioma, including astrocytoma, oligodendroglioma, and mixed gliomas, as determined by pre-registration central pathology review (Phase I)
  • Histological confirmation of glioblastoma multiforme (grade 4 astrocytoma) as determined by pre-registration central pathology review; note: gliosarcomas and other grade 4 astrocytoma variants (e.g., giant cell) are eligible (Phase II)
  • Evidence of tumor progression by MRI or computed tomography (CT) scan following radiation therapy or following the most recent anti-tumor therapy; note: 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; note: patients who have had a gross total resection (GTR) are eligible on the basis of evaluable disease
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, or 2
  • Absolute neutrophil count (ANC) ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • 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 x 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 UPC ratio; for UPC ratio ≥ 1.0, 24-hour urine protein must be obtained and the level should be < 1,000 mg for registration
  • Fixed or decreasing dose of corticosteroids (or no corticosteroids) ≥ 7 days prior to registration
  • Calculated glomerular filtration rate (GFR) must be ≥ 60 ml/min; GFR will be calculated as needed per institutional guidelines
  • Any number of prior chemotherapy regimens for recurrent disease (Phase I); ≤ 1 chemotherapy or other non-antiangiogenic regimen for recurrent disease (Phase II)
  • 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
  • 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
  • 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 discontinue use of medications that inhibit platelet function ≥ 10 days prior to registration; aspirin at doses greater than 325 mg/day must be discontinued ≥ 10 days prior to registration and avoided through the study; note: nonsteroidal antiinflammatory drug (NSAID) medications are recommended in place of aspirin; if NSAIDs or aspirin are used, histamine (H)-2 blockers and proton pump inhibitor (PPI) medications are recommended
  • Willing to provide mandatory blood and tissue samples for correlative research purposes (Phase I and II)

Exclusion Criteria:

  • Any 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
  • Prior hypersensitivity to bevacizumab or toxicity requiring discontinuation of bevacizumab (Phase I)
  • Any prior exposure to any VEGF or VEGF inhibitor including, but not limited to, bevacizumab, cediranib, vandetanib, sunitinib, pazopanib, aflibercept, or sorafenib (Phase II)
  • Prior hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies (Phase I and II)
  • Prior hypersensitivity to triptan derivatives (Phase I and II)
  • 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
  • Uncontrolled infection
  • Immunocompromised patients or patients known to be human immunodeficiency virus (HIV) positive and currently receiving combination antiretroviral therapy; patients known to be HIV positive, but without clinical evidence of an immunocompromised state, are eligible for this trial
  • 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
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of hypertensive crisis or hypertensive encephalopathy
  • 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
  • Evidence or history of bleeding diathesis (greater than normal risk of bleeding, i.e., hereditary hemorrhagic telangiectasia type I or HHT-1) or coagulopathy in the absence of therapeutic anti-coagulation or any hemorrhage/bleeding event > grade 3 within 4 weeks prior to registration; note: patients with 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
  • Receiving any other investigational agent that would be considered as a treatment for the primary neoplasm
  • Prior treatment with TRC105
  • Serious or non-healing wound, active ulcer, or untreated bone fracture
  • History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess ≤ 6 months prior to registration
  • History of 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
  • History of significant vascular disease (i.e., aortic aneurysm requiring surgical repair, or recent peripheral arterial thrombosis) within 6 months prior to registration

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Scottsdale/Phoenix, Ariz.

Mayo Clinic principal investigator

Evanthia Galanis, M.D.

Closed for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

Evanthia Galanis, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Evanthia Galanis, M.D.

Open for enrollment

Cancer Center Clinical Trials Referral Office

855-776-0015