Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer

Phase 2

Completed

Conditions: Adult Anaplastic Astrocytoma
Adult Anaplastic Ependymoma
Adult Anaplastic Meningioma
Adult Anaplastic Oligodendroglioma
Adult Brain Stem Glioma
Adult Central Nervous System Germ Cell Tumor
Adult Choroid Plexus Tumor
Adult Diffuse Astrocytoma
Adult Ependymoma
Adult Grade II Meningioma

Interventions: Drug: placebo
Drug: bevacizumab
Procedure: magnetic resonance imaging
Procedure: quality-of-life assessment

Registration Number: NCT00492089

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Bevacizumab may reduce CNS side effects caused by radiation therapy. This randomized phase II trial is studying how well bevacizumab works in reducing CNS side effects in patients who have undergone radiation therapy to the brain for primary brain tumor, meningioma, or head and neck cancer.

Detailed Description: PRIMARY OBJECTIVE:

I. Determine to what extent bevacizumab can reduce active radiation toxicity to the CNS in patients who have undergone cranial irradiation for primary brain neoplasm, meningioma, or head and neck cancer.

SECONDARY OBJECTIVES:

I. Determine to what extent this drug can reduce dexamethasone dependence in these patients.

II. Determine to what extent this drug can improve neurologic function in these patients.

III. Determine to what extent this drug can improve quality of life of these patients.

OUTLINE: This is a randomized, placebo-controlled, crossover, double-blind study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients in arm II who have failed to respond to treatment at 6 or 12 weeks may cross over to arm I and receive 2 courses of bevacizumab as in arm I. Patients in arm I (including crossover patients) who have responded to treatment may receive 2 additional courses of bevacizumab.

Patients undergo MRI after courses 2 and 4.

Quality of life and neurologic function are assessed at baseline, periodically during study treatment, and at 12 and 24 weeks after completion of study treatment.

After completion of study treatment, patients are followed at 12 and 24 weeks.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 11

Inclusion Criteria

No evidence of bleeding diathesis or coagulopathy
Fertile patients must use effective contraception during and for >= 2 months after completion of study therapy
No diarrhea >= grade 1
Histologically confirmed primary brain neoplasm, meningioma, or head and neck cancer [WHO grade 2 or 3 disease--no WHO grade 4 primary brain neoplasms (i.e., glioblastoma or gliosarcoma)]
Patients with head and neck cancer must not have any of the following:
- Evidence of metastatic disease
- Evidence of tumor invasion to major vessels (e.g., the carotid)
- History of bleeding related to tumor or radiotherapy during or after completion of radiotherapy
Must have undergone cranial irradiation
Must have radiographic evidence to support the diagnosis of radiation necrosis and/or surgical biopsy evidence of necrosis without tumor within the past 2 months
Must have evidence of progressive neurologic signs or symptoms appropriate to the location of the radiation necrosis
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
No significant traumatic injury within the past 28 days
No evidence of active CNS hemorrhage
Karnofsky performance status 60-100%
No clinically significant cardiovascular disease, including any of the following:
- Inadequately controlled hypertension (i.e., systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg despite antihypertensive medication)
- Large vessel cerebrovascular accident within the past 6 months
- Myocardial infarction or unstable angina within the past 6 months
No clinically significant cardiovascular disease, including any of the following:
- NYHA class II-IV congestive heart failure
- Serious or inadequately controlled cardiac arrhythmia
- Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
- Clinically significant peripheral vascular disease
At least 6 months since prior radiotherapy
Platelet count > 75,000/mm^3
Granulocyte count > 1,500/mm^3
Creatinine < 1.0 times ULN
AST < 2.5 times ULN
Not pregnant or nursing
Negative pregnancy test
Prior chemotherapy for tumor allowed
Prior tyrosine kinase inhibitors of VEGF receptor (VEGFR) allowed
More than 28 days since prior and no concurrent major surgical procedure or open biopsy
Concurrent dexamethasone allowed provided patient is on a stable dose for >= 1 week prior to study entry
Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met:
- In-range INR (usually between 2 and 3) and patient is on a stable dose of oral anticoagulant for 1 week or on a stable dose of low molecular weight heparin
- No active bleeding or pathological condition that carries a high risk of bleeding
Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met: No evidence of serious or nonhealing wound, ulcer, or bone fracture
No concurrent chemotherapy or tyrosine kinase inhibitors of VEGFR
No prior bevacizumab
More than 7 days since prior core biopsy
History of seizures allowed provided the patient is receiving anticonvulsant therapy
Hemoglobin >= 9.0 g/dL
Bilirubin =< 1.5 times upper limit of normal (ULN)
No other concurrent investigational agents

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I	magnetic resonance imaging	Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm II	magnetic resonance imaging	Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm II	quality-of-life assessment	Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm I	quality-of-life assessment	Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm II	placebo	Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Arm I	bevacizumab	Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Response ( > 25% Reduction in T2 Flair) From Baseline to Evaluation at 6 Weeks Post Treatment	Baseline to 12 weeks	Change in magnetic resonance imaging (MRI) from baseline to evaluation at 6 weeks for participants where MRI changes are based on the size of edema (T2 FLAIR) and Gd-contrast enhancement (lesion diameter and perfusion/dynamic). A 25% reduction in T2 flair volume constitutes a response for study.

Secondary Outcome Measures