A Study to Evaluate Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme (BRAIN)

NCT00345163 | Completed Phase 2

• 1 other identifier: AVF3708g
• Study Type: interventional
• Target: 167
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase II, open-label, multicenter, randomized, non comparative study consisting of two concurrent single-arms. Approximately 160 subjects will be randomized in a 1:1 ratio to Arm 1 (bevacizumab alone) or Arm 2 (bevacizumab + irinotecan).

Conditions

Glioblastoma

Keywords

Glioblastoma Multiforme; Avastin; Brain Cancer; GBM

Outcome Measures

Primary Outcomes (2)

• Objective response, as determined by the independent review facility (IRF)

  Complete response or partial response, determined on two consecutive assessments ≥4 weeks apart

• Progression-free survival, as determined by the IRF

  6 months

Secondary Outcomes (3)

• Incidence of adverse events and serious adverse events

  Length of patient on study

• Duration of objective response, as determined by the IRF

  Complete or partial response determined on two consecutive assessments ≥4 weeks apart

• Overall survival

  Time from randomization to death

Study Arms (2)

1

EXPERIMENTAL

Drug: bevacizumab

2

EXPERIMENTAL

Drug: bevacizumab; Drug: irinotecan

Interventions

bevacizumab DRUG

Intravenous repeating dose

1; 2

irinotecan DRUG

Intravenous repeating dose

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form
• Age ≥ 18 years
• Histologically confirmed GBM in first or second relapse
• Radiographic demonstration of disease progression following prior therapy
• Bi-dimensionally measurable disease with a minimum measurement of 1 cm (10 mm) in one diameter on MRI performed within 14 days prior to first treatment (Day 0)
• An interval of ≥ 4 weeks since prior surgical resection
• Prior standard radiation for GBM
• Prior chemotherapy: first-relapse subjects
• Prior chemotherapy: second-relapse subjects
• Recovery from the effects of prior therapy, including the following: 4 weeks from cytotoxic agents (except 6 weeks from nitrosoureas, 3 weeks from procarbazine, 2 weeks from vincristine); 4 weeks from any investigational agent; 1 week from non-cytotoxic agents; 8 weeks from radiotherapy to minimize the potential for MRI changes related to radiation necrosis that might be misdiagnosed as progression of disease, or 4 weeks if a new lesion, relative to the pre-radiation MRI, develops that is outside the primary radiation field
• Prior therapy with gamma knife or other focal high-dose radiation is allowed but the subject must have subsequent histologic documentation of recurrence, unless the recurrence is a new lesion outside the irradiated field
• Karnofsky performance status ≥ 70
• Life expectancy \> 12 weeks
• Use of an effective means of contraception in males and in females of childbearing potential
• Ability to comply with study and follow-up procedures

You may not qualify if:

• Prior treatment with irinotecan, bevacizumab, or another VEGF or VEGFR-targeted agent
• Prior treatment with prolifeprospan 20 with carmustine wafer
• Prior intracerebral agents
• Need for urgent palliative intervention for primary disease (e.g., impending herniation)
• Evidence of recent hemorrhage on baseline MRI of the brain with the following exceptions: Presence of hemosiderin; Resolving hemorrhagic changes related to surgery; Presence of punctate hemorrhage in the tumor
• Received more than two treatment regimens for Grade III and/or Grade IV glioma
• Blood pressure of \> 150 mmHg systolic and \> 100 mmHg diastolic
• History of hypertensive encephalopathy
• New York Heart Association (NYHA) Grade II or greater CHF
• History of myocardial infarction or unstable angina within 6 months prior to Day 0
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Significant vascular disease (e.g., aortic aneurysm, aortic dissection) or recent peripheral arterial thrombosis within 6 months prior to Day 0
• Evidence of bleeding diathesis or coagulopathy
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0
• History of intracerebral abscess within 6 months prior to Day 0

Sponsors & Collaborators

• Genentech, Inc.: lead

Related Publications (4)

• Friedman HS, Prados MD, Wen PY, Mikkelsen T, Schiff D, Abrey LE, Yung WK, Paleologos N, Nicholas MK, Jensen R, Vredenburgh J, Huang J, Zheng M, Cloughesy T. Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol. 2009 Oct 1;27(28):4733-40. doi: 10.1200/JCO.2008.19.8721. Epub 2009 Aug 31.

  PMID: 19720927 RESULT

• Ellingson BM, Hagiwara A, Morris CJ, Cho NS, Oshima S, Sanvito F, Oughourlian TC, Telesca D, Raymond C, Abrey LE, Garcia J, Aftab DT, Hessel C, Rachmilewitz Minei T, Harats D, Nathanson DA, Wen PY, Cloughesy TF. Depth of Radiographic Response and Time to Tumor Regrowth Predicts Overall Survival Following Anti-VEGF Therapy in Recurrent Glioblastoma. Clin Cancer Res. 2023 Oct 13;29(20):4186-4195. doi: 10.1158/1078-0432.CCR-23-1235.

  PMID: 37540556 DERIVED

• Ellingson BM, Harris RJ, Woodworth DC, Leu K, Zaw O, Mason WP, Sahebjam S, Abrey LE, Aftab DT, Schwab GM, Hessel C, Lai A, Nghiemphu PL, Pope WB, Wen PY, Cloughesy TF. Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials. Neuro Oncol. 2017 Jan;19(1):89-98. doi: 10.1093/neuonc/now187. Epub 2016 Aug 31.

  PMID: 27580889 DERIVED

• Ellingson BM, Kim HJ, Woodworth DC, Pope WB, Cloughesy JN, Harris RJ, Lai A, Nghiemphu PL, Cloughesy TF. Recurrent glioblastoma treated with bevacizumab: contrast-enhanced T1-weighted subtraction maps improve tumor delineation and aid prediction of survival in a multicenter clinical trial. Radiology. 2014 Apr;271(1):200-10. doi: 10.1148/radiol.13131305. Epub 2013 Nov 27.

  PMID: 24475840 DERIVED

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms

Interventions

Bevacizumab; Irinotecan

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Jane Huang, M.D.

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: June 23, 2006
• First Posted: June 27, 2006
• Study Start: July 1, 2006
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: May 16, 2017

Record last verified: 2017-05