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

This study has been completed.
Sponsor:
Information provided by:
Genentech
ClinicalTrials.gov Identifier:
NCT00345163
First received: June 23, 2006
Last updated: February 28, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
Glioblastoma
Drug: bevacizumab
Drug: irinotecan
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II, Multicenter, Randomized, Non-Comparative Clinical Trial to Evaluate the Efficacy and Safety of Bevacizumab Alone or in Combination With Irinotecan for Treatment of Glioblastoma Multiforme in First or Second Relapse

Resource links provided by NLM:


Further study details as provided by Genentech:

Primary Outcome Measures:
  • Objective response, as determined by the independent review facility (IRF) [ Time Frame: Complete response or partial response, determined on two consecutive assessments ≥4 weeks apart ] [ Designated as safety issue: No ]
  • Progression-free survival, as determined by the IRF [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events and serious adverse events [ Time Frame: Length of patient on study ] [ Designated as safety issue: No ]
  • Duration of objective response, as determined by the IRF [ Time Frame: Complete or partial response determined on two consecutive assessments ≥4 weeks apart ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Time from randomization to death ] [ Designated as safety issue: No ]

Enrollment: 167
Study Start Date: July 2006
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: bevacizumab
Intravenous repeating dose
Experimental: 2 Drug: bevacizumab
Intravenous repeating dose
Drug: irinotecan
Intravenous repeating dose

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, anticipation of need for major surgical procedure during the course of the study
  • Minor surgical procedures (excluding placement of a vascular access device), stereotactic biopsy, fine needle aspirations, or core biopsies within 7 days prior to Day 0
  • Serious non-healing wound, ulcer, or bone fracture
  • Pregnancy (positive pregnancy test) or lactation
  • Known hypersensitivity to any component of bevacizumab
  • History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix)
  • Pregnant or nursing females
  • Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmia requiring medication
  • Subjects unable to undergo an MRI with contrast
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00345163

Sponsors and Collaborators
Genentech
Investigators
Study Director: Jane Huang, M.D. Genentech
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Clinical Trials Posting Group, Genentech, Inc.
ClinicalTrials.gov Identifier: NCT00345163     History of Changes
Other Study ID Numbers: AVF3708g
Study First Received: June 23, 2006
Last Updated: February 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech:
Glioblastoma Multiforme
Avastin
Brain Cancer
GBM

Additional relevant MeSH terms:
Glioblastoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Irinotecan
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Phytogenic
Radiation-Sensitizing Agents
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 18, 2014