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

NCT00795665 | Completed Phase 2 Results DMC

• 3 other identifiers: 224865UCDCC#208P30CA093373
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

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.

Conditions

Glioma

Keywords

adult anaplastic astrocytoma; adult glioblastoma; adult gliosarcoma; adult giant cell glioblastoma; adult anaplastic oligodendroglioma; adult mixed glioma; recurrent adult brain tumor

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

  Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years).

Secondary Outcomes (4)

• Radiographic Response to Therapy

  One year

• Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema

  One year

• Safety and Toxicity

  One year

• Overall Survival

  Time from first day of treatment to time of death due to any cause (up to 7 years).

Study Arms (1)

Bevacizumab and Carmustine

EXPERIMENTAL

Drug: bevacizumab; Drug: carmustine

Interventions

bevacizumab 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.

Also known as: Avastin

Bevacizumab and Carmustine

carmustine 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.

Also known as: BCNU

Bevacizumab and Carmustine

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, Davis: lead
• National Cancer Institute (NCI): collaborator
• Genentech, Inc.: collaborator

Study Sites (1)

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

MeSH Terms

Conditions

Glioma; Astrocytoma; Glioblastoma; Gliosarcoma; Oligodendroglioma; Brain Neoplasms

Interventions

Bevacizumab; Carmustine

Condition Hierarchy (Ancestors)

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; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds

Limitations and Caveats

The PI has indicated that data were uninterpretable for the outcome measures in this study.

Results Point of Contact

• Title: Analyst
• Organization: University of California Davis

nlogihara@ucdavis.eduu

916-734-8053

Study Officials

• Robert T. O'Donnell, MD, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2008
• First Posted: November 21, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: May 12, 2020
• Results First Posted: May 12, 2020

Record last verified: 2020-05

Locations

US (1)