Bevacizumab and Carmustine in Treating Patients With Relapsed or Progressive High-Grade Glioma

NCT ID: NCT00795665

Last Updated: 2020-05-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2015-12-31

Brief Summary

RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Drugs used in chemotherapy, such as carmustine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with carmustine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with carmustine works in treating patients with relapsed or progressive high-grade glioma.

Detailed Description

OBJECTIVES:

Primary

• To determine the 6-month progression-free survival of patients with relapsed or progressive high-grade gliomas treated with bevacizumab and carmustine.

Secondary

• To evaluate the radiographic response to this regimen as measured by MRI and PET scan with image fusion.
• To utilize novel brain imaging to differentiate between a radiographic response due to tumor shrinkage and a radiographic response due to decreased vasogenic edema.
• To evaluate the safety and toxicity of this regimen in these patients.
• To evaluate the overall survival of these patients.

OUTLINE: Patients receive bevacizumab IV on days -7, 8, 22, 36, and 50 of course 1 and on days 8, 22, 36, and 50 of all subsequent courses. Patients also receive carmustine IV over 4 hours on day 1. Treatment repeats every 56 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed every 3 months.

Conditions

Glioma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Bevacizumab and Carmustine

Group Type: EXPERIMENTAL

bevacizumab

Intervention Type: DRUG

Bevacizumab (10 mg/kg) will be given intravenously every other week starting one week before the first dose of BCNU. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.

carmustine

Intervention Type: DRUG

BCNU (200 mg/m2), will be given over 4 hours as a continuous intravenous infusion every 8 weeks. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.

Interventions

bevacizumab

Bevacizumab (10 mg/kg) will be given intravenously every other week starting one week before the first dose of BCNU. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.

Intervention Type: DRUG

carmustine

BCNU (200 mg/m2), will be given over 4 hours as a continuous intravenous infusion every 8 weeks. Treatment with both BCNU and bevacizumab for 6-months, after which the participant may continue to receive bevacizumab every 2 weeks for a maximum of one year and three additional cycles of BCNU.

Intervention Type: DRUG

Other Intervention Names

Avastin; BCNU

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed GBM, anaplastic astrocytoma, anaplastic oligoastrocytoma or anaplastic oligodendroglioma.
• Disease progression (confirmed by MRI, PET or both) after radiation therapy
• At least 28 days have elapsed since chemotherapy, major surgery or radiation therapy.
• No other malignancy within 3 years except for non-melanomatous skin cancer or in situ cervical cancer.
• Karnofsky performance score at least 70
• Platelet count ≥ 130/mm3.
• Absolute neutrophil count ≥ 1500/mm3
• Calculated creatinine clearance greater than 45 mg/dl
• AST < 2 times the upper limit of normal
• Bilirubin < 1.5 times the upper limit of normal
• Ability to give signed informed consent
• Patients must be 18 years of age or older.

Exclusion Criteria

• Prior intravenous or oral nitrosoureas (BCNU, CCNU) or prior VEGF targeted therapy including bevacizumab. No more than two prior chemotherapy regimens are allowed. Prior or current steroid use is allowed.
• Evidence of CNS hemorrhage
• Requirement for therapeutic anticoagulation
• Any grade 3 or greater hemorrhage within the previous 28 days
• Active inflammatory bowel disease
• Inadequately controlled hypertension
• Any prior history of hypertensive crisis or hypertensive encephalopathy
• New York Heart Association Grade II or greater congestive heart failure
• History of myocardial infarction or unstable angina within 6 months prior to study enrollment
• History of stroke or transient ischemic attack within 6 months prior to study enrollment
• Significant vascular disease
• Symptomatic peripheral vascular disease
• Evidence of bleeding diathesis or coagulopathy
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
• Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
• Serious, non-healing wound, ulcer, or bone fracture
• Proteinuria at screening
• Pregnant (or lactating). Use of effective means of contraception in subjects of child-bearing potential
• Prior organ transplantation
• Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• Known acquired immune deficiency syndrome (AIDS) or HIV positive status

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Genentech, Inc.

INDUSTRY

Sponsor Role: collaborator

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert T. O'Donnell, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Locations

University of California Davis Cancer Center

Sacramento, California, United States

Countries

United States

Other Identifiers

UCDCC#208

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA093373

Identifier Type: NIH

Identifier Source: secondary_id

View Link

224865

Identifier Type: -

Identifier Source: org_study_id