NCT01609790|CompletedPhase 2Results

Bevacizumab With or Without Trebananib in Treating Patients With Recurrent Brain Tumors

Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma

National Cancer Institute (NCI)ClinicalTrials.gov

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6 other identifiers

NCI-2012-01969S13-00759CDR0000734205RTOG-1122U10CA180868U10CA021661

Study Type

interventional

Target

137

Locations

2 countries

Sites

244

Timeline

RegisteredJun 2012

StartedJun 2012

CompletionMay 2022

Brief 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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

137

participants targeted

Target at P75+ for phase_2

Timeline

Completed

Started Jun 2012

Longer than P75 for phase_2

Geographic Reach

2 countries

244 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

10 years study duration

First Submitted

Initial submission to the registry

May 30, 2012

Completed

2 days until next milestone

First Posted

Study publicly available on registry

June 1, 2012

Completed

3 days until next milestone

Study Start

First participant enrolled

June 4, 2012

Completed

3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 2, 2015

Completed

1.4 years until next milestone

Results Posted

Study results publicly available

February 27, 2017

Completed

5.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2022

Completed

Last Updated

July 21, 2022

Status Verified

May 1, 2022

Enrollment Period

3.3 years

First QC Date

May 30, 2012

Results QC Date

October 25, 2016

Last Update Submit

June 28, 2022

Conditions

Giant Cell Glioblastoma Glioblastoma Gliosarcoma Oligodendroglioma Recurrent Brain Neoplasm Recurrent Glioblastoma

Outcome Measures

Primary Outcomes (2)

Number of Patients Experiencing of Dose-limiting Toxicity (Cohort 1)
Dose-limiting toxicity (DLT), defined as a clinically significant adverse event or abnormal laboratory value assessed as unrelated to disease progression, intercurrent illness, or concomitant medications and meets any of the criteria below. Any DLT must be a toxicity possibly related to protocol treatment during first 4 weeks: grade 4 hematologic toxicity, grade 3/4 thrombocytopenia, or grade 3/4 non-hematologic toxicity; Gastrointestinal fistula, bowel perforation, intracranial hemorrhage, wound dehiscence, or reversible posterior leukoencephalopathy of any grade; Delay of treatment \> 28 days. If 2+ of patients experience a DLT among 6 eligible patients, this drug combination will be considered unsafe and a lower dose of AMG will be explored; otherwise conclude that this drug combination is safe. The probability of claiming safe dose is no more than 16% when the true DLT rate is \>45%, and the probability of claiming safe dose is at least 78% when the true DLT rate is \<= 15%.
From start of treatment to 4 weeks.
Six-month Progression-free Survival (Cohort 2)
As determined by central review of MRI exams, assessed using RANO criteria for progression that is defined by any of the following: \> 25% increase in sum of the products of perpendicular diameters of enhancing lesions compared to the smallest tumor measurement obtained either at baseline (if no decrease) or best response, on stable or increasing doses of corticosteroids; Significant increase in T2/FLAIR non-enhancing lesion on stable or increasing doses of corticosteroids compared to baseline scan or best response following initiation of therapy, not due to co-morbid events; Any new lesion; Clear clinical deterioration not attributable to other causes apart from the tumor or changes in corticosteroid dose; Failure to return for evaluation due to death or deteriorating condition; Clear progression of non-measurable disease.
From randomization to six months.

Secondary Outcomes (5)

Incidence of Grade 3+ Treatment-related Toxicity, Measured by CTCAE v. 4 (Cohort 2)
From start of treatment up to 3 years.
Overall Survival (Cohort 2)
From randomization up to 3 years.
Progression-free Survival (Cohort 2)
From randomization up to 3 years.
Radiographic Response Rate (Cohort 2)
From randomization up to 3 years.
Percentage of Patients Requiring Dose Reduction/Interruption or Discontinuation in the First 2 and Subsequent Courses (Cohort 1)
From randomization up to 3 years.

Other Outcomes (1)

Tumor Genotype, Expression Profile, and Circulating Angiogenesis Biomarkers (Cohort 2)
From randomization to date of death or last followup. Statistical analysis occurs when tumor genotype, expression profile and circulating angiogenesis biomarkers have been determined from the tissue specimens.

Study Arms (2)

Arm I (bevacizumab and trebananib)

EXPERIMENTAL

Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: BevacizumabOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyBiological: Trebananib

Arm II (bevacizumab and placebo)

ACTIVE COMPARATOR

Patients receive bevacizumab as in Arm I and placebo IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross over to Arm I.

Biological: BevacizumabOther: Laboratory Biomarker AnalysisOther: Pharmacological StudyOther: Placebo Administration

Interventions

BevacizumabBIOLOGICAL

Given IV

Also known as: ABP 215, Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF Monoclonal Antibody SIBP04, Anti-VEGF rhuMAb, Avastin, Bevacizumab awwb, Bevacizumab Biosimilar ABP 215, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Bevacizumab Biosimilar CBT 124, Bevacizumab Biosimilar CT-P16, Bevacizumab Biosimilar FKB238, Bevacizumab Biosimilar GB-222, Bevacizumab Biosimilar HD204, Bevacizumab Biosimilar HLX04, Bevacizumab Biosimilar IBI305, Bevacizumab Biosimilar LY01008, Bevacizumab Biosimilar MIL60, Bevacizumab Biosimilar Mvasi, Bevacizumab Biosimilar MYL-1402O, Bevacizumab Biosimilar QL 1101, Bevacizumab Biosimilar RPH-001, Bevacizumab Biosimilar SCT501, Bevacizumab Biosimilar Zirabev, Bevacizumab-awwb, Bevacizumab-bvzr, BP102, BP102 Biosimilar, HD204, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Mvasi, MYL-1402O, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF, SCT501, SIBP 04, SIBP-04, SIBP04, Zirabev

Arm I (bevacizumab and trebananib)Arm II (bevacizumab and placebo)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (bevacizumab and trebananib)Arm II (bevacizumab and placebo)

Pharmacological StudyOTHER

Correlative studies

Arm I (bevacizumab and trebananib)Arm II (bevacizumab and placebo)

Placebo AdministrationOTHER

Given IV

Arm II (bevacizumab and placebo)

TrebananibBIOLOGICAL

Given IV

Also known as: AMG 386, AMG386, Angiopoietin 1/2-Neutralizing Peptibody AMG 386

Arm I (bevacizumab and trebananib)

Eligibility Criteria

Age18 Years+

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
+6 more criteria

You may not qualify if:

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
+9 more criteria

Contact the study team to confirm eligibility.