Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00595322

Collaborator

Weill Medical College of Cornell University (Other), Genentech, Inc. (Industry)

Enrollment

Locations

Arm

137

Actual Duration (Months)

12.5

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a pilot study. The goal of this study is to test whether Bevacizumab is safe enough in patients with brain tumors so that a larger study can be conducted. This study will also give us some information about whether the combination of Bevacizumab and radiation has potential to become an effective treatment for regrowing brain tumors.

Bevacizumab is an experimental drug that blocks a molecule called VEGF that is found in high amounts in malignant gliomas. VEGF promotes the growth of blood vessels that bring nutrients to tumor cells. In studies with laboratory animals, Bevacizumab slowed the growth of several different types of human cancer cells by blocking the effects of VEGF. There is also evidence that Bevacizumab enhances the effects of radiation on tumor cell

Condition or Disease	Intervention/Treatment	Phase
Brain Cancer Recurrent Malignant Gliomas Primary Brain Tumor	Other: bevacizumab and radiation (IMRT)	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Safety of Bevacizumab in the Radiation Treatment of Recurrent Malignant Glioma: A Pilot Study

Actual Study Start Date :

Dec 1, 2005

Actual Primary Completion Date :

May 1, 2017

Actual Study Completion Date :

May 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 bevacizumab and radiation (IMRT)	Other: bevacizumab and radiation (IMRT) bevacizumab 10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (cycle defined as 28 days). If the tumor volume remains < 40 cc, the patient will undergo stereotactic radiotherapy with IMRT (30Gy) beginning anywhere from day 7-10 of cycle 2 (5 doses of 6 Gy over 2 and a half weeks)

Arm

Intervention/Treatment

Experimental: 1

bevacizumab and radiation (IMRT)

Other: bevacizumab and radiation (IMRT)

bevacizumab 10 mg/kg IV once every two weeks on days 1 and 15 of every cycle (cycle defined as 28 days). If the tumor volume remains < 40 cc, the patient will undergo stereotactic radiotherapy with IMRT (30Gy) beginning anywhere from day 7-10 of cycle 2 (5 doses of 6 Gy over 2 and a half weeks)

Outcome Measures

Primary Outcome Measures

To test the safety of bevacizumab in patients with recurrent malignant gliomas in preparation for a larger study to test the efficacy of this drug used during the initial radiation treatment of these tumors if safety is affirmed. [conclusion of study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Recurrent malignant glioma that has failed prior radiotherapy and/or chemotherapy. Surgery for the recurrence may be offered to selected patients prior to receiving bevacizumab and IMRT on this protocol.
MRI scan with gadolinium contrast showing geographically-circumscribed tumor < than or equal to 3.5cm. (Scan must be performed on a steroid dosage that has been stable for at least 5 days. If the steroid dose is increased between date of imaging and registration, a new baseline MRI is required).
Patients must have recovered from the toxic effects of prior therapy:
An interval of > than or equal to 4 weeks (28 days) from prior cytotoxic therapy
An interval of > than or equal to 1 week (7 days) from any non-cytotoxic agents
An interval of > than or equal to 6 weeks (42 days) from the completion of radiation therapy
Absolute neutrophil count > than or equal to 1,500/mm3.
Platelet count > than or equal to 100,000/mm3.
Hemoglobin > than or equal to 10 g/dl.
BUN and serum creatinine both < 1.5 times upper limit of normal.
Total bilirubin both < 1.5 times upper limit of normal.
SGOT and SGPT both < than or equal to 3 times upper limit of normal.
Alkaline phosphatase < than or equal to 2 times upper limit of normal.
than or equal to 18 years of age.
Karnofsky Performance Score > or equal to 70
Life expectancy > or equal to 12 weeks
Men and women with reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment.
Patient or their legal proxy must provide written informed consent prior to registration on study.

Exclusion Criteria:

Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored bevacizumab cancer study.
Blood pressure >150 mmHg systolic and/or >100 mmHg diastolic
Any prior history of hypertensive crisis or hypertensive encephalopathy
Unstable angina within 12 months of study enrollment
CTC 3.0 Grade 2 or greater congestive heart failure
History of myocardial infarction within 12 months of study enrollment
History of stroke or transient ischemic attack at any time
Known CNS disease
Known hypersensitivity to any component of bevacizumab
History of peptic ulcer within the last 6 months
Clinically significant peripheral vascular disease
Evidence of bleeding diathesis or coagulopathy
Use of ongoing anticoagulants or antiplatelet agents (aspirin, NSAIDS, etc)
Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to the first dose of bevacizumab or anticipation of need for major surgical procedure during the course of the study. (Recently resected patients may be enrolled on-study two weeks post-surgery. However, treatment with Bevacizumab will not begin until 28 days after the surgical procedure for all patients.)
Craniotomy wound that has not sufficiently healed
Minor surgical procedures, fine needle aspirations or core biopsies within 7 days prior to study enrollment
Pregnant (positive pregnancy test) or lactating
Urine protein:creatinine ratio ≥1.0 at screening
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
Lung carcinoma of squamous cell histology or any histology in close proximity to a major vessel, cavitation, or history of hemoptysis
Inability to comply with study and/or follow-up procedures
Glioma showing prior spontaneous hemorrhage as determined from the clinical history or from any preoperative CT or MRI scan.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan-Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065