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

Phase 2

Completed

Conditions: Glioma

Interventions: Drug: bevacizumab
Drug: carmustine

Registration Number: NCT00795665

Lead Sponsor: University of California, Davis

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bevacizumab and Carmustine	bevacizumab	-
Bevacizumab and Carmustine	carmustine	-

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	Time from first day of treatment to the first observation of disease progression or death due to any cause (up to 7 years).	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.

Secondary Outcome Measures

Name	Time	Method
Radiographic Response to Therapy	One year	Response measured using MRI and PET with image fusion
Differentiate a Radiographic Response Due to Tumor Shrinkage From a Radiographic Response Due to Decreased Vasogenic Edema	One year	Measurements made by novel brain imaging
Safety and Toxicity	One year	Subjects will be assessed clinically for toxicity prior to, during, and after each infusion. NCI CTCAE 3.0 Common Terminology Criteria (CTC) for Adverse Events for toxicity and Adverse Event Reporting will be utilized.
Overall Survival	Time from first day of treatment to time of death due to any cause (up to 7 years).