Bevacizumab and Temozolomide Following Radiation and Chemotherapy for Newly Diagnosed Glioblastoma Multiforme

• Status: Completed
• Trial end date: 2014-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is being conducted to help determine whether the addition of Avastin (an anti-cancer drug), when given along with temozolomide during the monthly cycles that follow radiation, is able to delay tumor growth, shrink tumors, or impact how long people with GBM live. This study is sponsored by Genentech, Inc., the manufacturer of Avastin.

Avastin is the experimental drug being administered in this research study. Avastin binds a protein called vascular endothelial growth factor, or VEGF. VEGF is produced by tumors and circulates in the blood. One of VEGF's main roles is to support the growth of new blood vessels. During cancer, VEGF promotes the growth of blood vessels that bring nutrients to tumor cells and help them grow. Avastin binds to VEGF, which then prevents VEGF from functioning. In laboratory studies, Avastin prevented the growth of several different types of cancer cells grown in animals. Avastin was approved by the Food and Drug Administration (FDA) for the treatment of metastatic colorectal cancer in combination with chemotherapy. Avastin has not been approved by the FDA for the treatment of GBM and is, therefore, considered experimental. Avastin is currently undergoing testing (alone and in combination with another anti-cancer drug, irinotecan) in persons with GBM that have come back after conventional treatment.

Temozolomide (Temodar) is an anti-cancer drug that works by interfering with the growth of cells (including cancer cells) by stopping their division. Temozolomide was approved by the U.S. FDA for the treatment of newly diagnosed GBM in 2005.

Avastin and temozolomide are currently being used together in several research studies involving people with newly diagnosed GBM. Limited information is available about either the safety or effectiveness of this drug combination.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Chicago
• Collaborator: Genentech, Inc.
• Treatments: Bevacizumab; Dacarbazine; Polystyrene sulfonic acid; Temozolomide

Criteria

Inclusion Criteria:

1. Disease-Specific Concerns Histologically confirmed GBM as determined by central pathology review Supratentorial location

2. General Medical Concerns 18 years of age; Karnofsky performance status > 60; Tumor-related contrast enhancement on initial and post-operative Gd-MRI; Recovery from effects of surgery and/or its complications prior to initiating radiotherapy; Radiotherapy must begin < 5 weeks following surgery; Pre-and post-operative Gd-MRI prior to the initiation of radiotherapy; Adequate hematological, renal, and hepatic function:hemoglobin > 10 grams hematocrit > 30%, platelets > 100,000 per mm3, BUN < 25 mg/dl, Creatinine < 1.5 mg/dl, Total bilirubin < 1.5 mg/dl, SGOT or SGPT < twice institutional normal range, Subjects must not be pregnant or nursing, Use of effective means of contraception (men and women) in subjects of child-bearing (women) and at all ages (men), Study-specific signed informed consent, Ability to comply with study follow-up procedures.

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Exclusion Criteria:

• a. Disease-Specific Concerns: malignant gliomas graded less than GBM; infratentorial tumor location; recurrent disease; intra-tumoral hemorrhage; Placement of Gliadel® wafers; b. Bevacizumab-Specific Concerns: Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications); Any prior history of hypertensive crisis or hypertensive encephalopathy; 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; New York Heart Association (NYHA) Grade II or greater CHF (see Appendix E); Significant vascular disease (e.g., aortic aneurysm, aortic dissection); Symptomatic peripheral vascular disease; Evidence of bleeding diathesis or coagulopathy; History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment; History of intracerebral abscess within 6 months prior to study enrollment; Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment (exclusive of craniotomy); 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; Serious non-healing wound, ulcer, or bone fracture; Proteinuria at screening as demonstrated by either; Urine protein:creatinine (UPC) ratio 1.0 at screening OR Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible); Known hypersensitivity to any component of Avastin. c. General Medical Exclusions

Subjects meeting any of the following criteria are ineligible for study entry:

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 Avastin cancer study; History of any other malignancy within 5 years (except non-melanoma skin cancer or carcinoma in situ of the cervix);Pregnant or nursing females; Unstable systemic disease, including active infection, uncontrolled hypertension, or serious cardiac arrhythmias requiring medication;

Screening clinical laboratory values:

Absolute neutrophil count < 1500/ul, Platelet count < 100,000/ul, Total bilirubin > 1.6 mg.dl, AST/ALT > 1.5 x the upper limit of normal ( ULN), Creatinine > 1.2 x ULN, Urine protein/creatinine ratio > 1.0, International normalized ration (INR) > 1.5 and activated partial thromboplastin time (aPTT) > 1.5 x ULN (except for subjects receiving anticoagulation therapy) in the absence of therapeutic intent to anticoagulate the subject. Therapeutic anticoagulation is permitted.