Bevacizumab With or Without Trebananib in Treating Patients With Recurrent Brain Tumors
Condition: Giant Cell Glioblastoma; Glioblastoma; Gliosarcoma; Oligodendroglioma; Recurrent Brain Neoplasm; Recurrent Glioblastoma
MeSH terms: Glioblastoma; Gliosarcoma; Oligodendroglioma; Brain Neoplasms; Recurrence
Intervention: Bevacizumab; Laboratory Biomarker Analysis; Pharmacological Study; Placebo Administration; Trebananib
Intervention description: Given IV; Correlative studies; Correlative studies; Given IV; Given IV
Intervention MeSH terms: Bevacizumab; Antineoplastic Agents, Immunological; Trebananib; Endothelial Growth Factors; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Immunoglobulin G
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 137.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This partially randomized phase II trial with a safety run-in component studies the side
      effects and how well bevacizumab given with or without trebananib works in treating patients
      with brain tumors that have come back (recurrent). Immunotherapy with monoclonal antibodies,
      such as bevacizumab, may induce changes in the body's immune system and interfere with the
      ability of tumor cells to grow and spread. Trebananib may stop the growth of tumor cells by
      blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together
      with trebananib is more effective than bevacizumab alone in treating brain tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically proven diagnosis of glioblastoma or variants (gliosarcoma, glioblastoma
             with oligodendroglial features, giant cell glioblastoma); patients will be eligible if
             the original histology was a lower grade glioma and a subsequent histological
             diagnosis of glioblastoma or variants is made

          -  The tumor must be supratentorial; patients with infratentorial disease, spinal cord
             disease, and/or leptomeningeal disease are excluded

          -  Patients must have shown unequivocal evidence for tumor progression on the previous
             treatment regimen (prior to enrollment on this study) by magnetic resonance imaging
             (MRI) scan of the brain with and without contrast within 14 days prior to
             registration; the dose of steroids must be stable or decreasing for at least 5 days
             prior to the scan; patients with tumor progression who then undergo surgical resection
             prior to enrollment on study may be eligible as long as pathology confirms progressive
             or recurrent glioblastoma multiforme (GBM) (or variants); for patients who undergo
             surgical resection, registration on study may not occur any sooner than 28 days from
             surgery; an MRI scan of the brain with and without contrast is still required within
             14 days prior to registration on study but is not required to demonstrate measurable
             disease or tumor progression after surgery

          -  Patients unable to undergo MRI because of non-compatible devices can be enrolled,
             provided computed tomography (CT) scans are obtained and are of sufficient quality;
             patients without non-compatible devices may not have CT scans performed to meet this
             requirement

          -  History/physical examination within 14 days prior to registration

          -  Karnofsky performance scale >= 70 within 14 days prior to registration

          -  Patients who have received prior treatment with interstitial brachytherapy,
             stereotactic radiosurgery, or implanted chemotherapy sources, such as wafers of
             polifeprosan 20 with carmustine, must have confirmation of progressive disease within
             14 days prior to registration based upon nuclear imaging, magnetic resonance (MR)
             spectroscopy, perfusion imaging, or histopathology

          -  Leukocytes > 3,000/mm^3 (within 14 days prior to registration)

          -  Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (within 14 days prior to
             registration)

          -  Hemoglobin >= 10.0 g/dL (note: the use of transfusion or other intervention to achieve
             hemoglobin [Hgb] >= 10.0 g/dL is acceptable) (within 14 days prior to registration)

          -  Platelets >= 100,000 cells/mm^3 (within 14 days prior to registration)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             < 2.5 X institutional upper limit of normal (within 14 days prior to registration)

          -  Bilirubin =< 2.0 mg/dL (within 14 days prior to registration)

          -  Creatinine within normal upper institutional limits or creatinine clearance > 60
             mL/min/1.73 m^2 (per 24 hour urine collection or calculated according to the
             Cockcroft-Gault formula) for subjects with creatinine levels above the institutional
             normal (within 14 days prior to registration)

               -  Patients with creatinine levels below normal institutional limits are eligible

          -  Prothrombin time (PT)/international normalized ratio (INR) =< 1.5 (within 14 days
             prior to registration)

          -  Urinary protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick (within 14 days prior
             to registration)

          -  Generally well-controlled blood pressure with systolic blood pressure =< 140 mm Hg AND
             diastolic blood pressure =< 90 mm Hg within 5 days prior to registration; the use of
             anti-hypertensive medications to control hypertension is permitted

          -  Women of childbearing potential must have a negative serum beta-human chorionic
             gonadotropin (HCG) pregnancy test within 14 days prior to registration

          -  Women of childbearing potential and male patients who are sexually active must
             practice adequate contraception during therapy and for 180 days (6 months) afterwards

          -  Patient must provide study specific informed consent prior to study entry

        Exclusion Criteria:

          -  Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free
             for a minimum of 3 years (for example, carcinoma in situ of the breast, oral cavity,
             or cervix are all permissible)

          -  Prior systemic cytotoxic chemotherapy within (i.e., =<) 28 days (42 days for
             nitrosoureas or mitomycin C) prior to registration, or patients who have not returned
             to baseline or =< Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v.
             4) grade 2 from adverse events (excluding alopecia) due to agents administered more
             than 28 days prior to registration

          -  Patients who received non-cytotoxic drug therapy must be off treatment for at least 14
             days prior to registration; prior treatment with anti-vascular endothelial growth
             factor (VEGF) targeted agents; AMG 386 therapy; or other molecules that inhibit
             angiopoietins or TEK tyrosine kinase, endothelial (Tie2) receptor including, but not
             limited to, XL-820, XL-184 (cabozantinib-s-malate), and CVX-060/PF-4856884 is not
             allowed regardless of time frame

          -  Patients who have not yet completed at least 21 days (30 days for prior monoclonal
             antibody therapy) since ending other investigational device or drug trials, or who are
             currently receiving other investigational treatments

          -  Treatment within 30 days prior to enrollment with strong immune modulators, including
             but not limited to systemic cyclosporine, tacrolimus, sirolimus, mycophenolate
             mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide, and
             targeted immune modulators such as abatacept (CTLA-4-Ig), adalimumab, alefacept,
             anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab

          -  Prior radiotherapy within 90 days (3 months) prior to registration unless there is
             either: a) histopathologic confirmation of recurrent tumor; or b) new enhancement on
             MRI outside of the radiation treatment field

          -  Major surgical procedure (including craniotomy and open brain biopsy) or significant
             traumatic injury within 28 days prior to registration or those patients who receive a
             non-central nervous system (CNS) minor surgical procedures (e.g. core biopsy or fine
             needle aspiration) within 3 days prior to registration; there is no waiting period for
             central line placement; there is a 7-day window for recovery prior to registration for
             patients who underwent stereotactic biopsy of the brain

          -  Prior therapy with anti-VEGF targeted agents (e.g. bevacizumab, cediranib, vandetanib,
             aflibercept, sunitinib, sorafenib, etc.); prior therapy with thalidomide and
             lenalidomide is allowed as long as treatment has not occurred within 30 days prior to
             enrollment

          -  More than 2 relapses

          -  Therapeutic anticoagulation with warfarin < 7 days prior to registration; (therapeutic
             or prophylactic therapy with aspirin, a low-molecular weight heparin, or a Factor Xa
             inhibitor is acceptable)

          -  Intratumoral hemorrhage or peritumoral hemorrhage, demonstrated by MRI or CT scan,
             CTCAE, v. 4 grade 2 or greater or evidence of significant hemorrhage (regardless of
             CTCAE, v. 4 grade) defined as > 1 cm diameter of blood (including postoperative
             hemorrhage)

          -  Gastrointestinal bleeding or any other hemorrhage/bleeding event CTCAE, v. 4 grade 3
             or greater within 30 days prior to study entry

          -  Severe, active co-morbidity, defined as follows:

               -  Unstable angina and/or congestive heart failure requiring hospitalization within
                  180 days (6 months) prior to registration

               -  Transmural myocardial infarction within 180 days (6 months) prior to registration

               -  History of stroke, cerebral vascular accident (CVA), or transient ischemic attack
                  within 180 days (6 months) prior to registration

               -  Acute bacterial or fungal infection requiring intravenous antibiotics at the time
                  of registration

               -  Chronic obstructive pulmonary disease exacerbation or other respiratory illness
                  requiring hospitalization or precluding study therapy at the time of registration

               -  Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects

               -  Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease
                  Control and Prevention (CDC) definition; note, however, that human
                  immunodeficiency virus (HIV) testing is not required for entry into this protocol

               -  Known coagulopathy that increases risk of bleeding or a history of clinically
                  significant hemorrhages in the past

               -  History of non-healing wounds or ulcers, or bone fractures within 90 days (3
                  months) prior to registration

               -  History of venous or arterial thromboembolism within 12 months prior to
                  registration

          -  Prior allergic reaction to the study drugs involved in this study