Clinical Trial Finder

Inclusion Criteria:

Patients have histologically confirmed diagnosis of WHO gr IV primary malignant glioma. Patients will be unresectable or have multifocal disease.

• - Age ≥ 18years & life expectancy of >12 weeks.

• - Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.

• - Interval of <1 week between prior biopsy/4 weeks from surgical resection & enrollment on protocol.

• - Karnofsky ≥60% - Hemoglobin ≥9g/dl, ANC ≥1,500 cells/microliter, platelets ≥125,000 cells/microliter.

• - Serum creatinine ≤1.5 mg/dl, serum SGOT & bilirubin ≤1.5 x ULN.

• - For patients on corticosteroids, they must have been on stable dose for 1 week prior to entry, if clinically possible, & dose should not be escalated over entry dose level.

• - Signed informed consent approved by IRB prior to patient entry.

• - No evidence of > grade 1 CNS hemorrhage on baseline MRI/CT scan.

• - If sexually active, patients will take contraceptive measures for duration of treatments.

Exclusion Criteria:

• - Pregnancy/breast feeding.

• - Co-medication that may interfere with study results.

• - Active infection requiring IV antibiotics.

• - Prior or current Treatment w XRT/chemo for brain tumor, irrespective of grade of tumor.

• - Evidence of > grade 1 CNS hemorrhage on baseline MRI or CT scan.

Avastin-Specific Concerns:

• - Inadequately controlled hypertension.

• - Any prior history of hypertensive crisis/hypertensive encephalopathy.

• - New York Heart Association Grade II or > congestive heart failure.

• - History of myocardial infarction/unstable angina < 6 months prior to study enrollment.

• - History of stroke/transient ischemic attack < 6 months prior to study enrollment.

• - Significant vascular disease.

• - Symptomatic peripheral vascular disease.

• - Evidence of bleeding diathesis/coagulopathy.

• - Major surgical procedure, open biopsy,/significant traumatic injury within 28 days prior to study enrollment/anticipation of need for major surgical procedure during course of study.

• - Core biopsy/other minor surgical procedure, excluding placement of vascular access device, <7 days prior to study enrollment.

• - History of abdominal fistula, GI perforation, /intra-abdominal abscess <6 months prior to study enrollment.

• - Serious, non-healing wound, ulcer, or bone fracture.

• - Proteinuria at screening as demonstrated by either.

• - UPC ratio ≥1.0 at screening OR.

• - Urine dipstick for proteinuria ≥2+ - Known hypersensitivity to any component of Avastin.

• - Pregnant/lactating.

Use of effective means of contraception in subjects of child-bearing potential. - Current, ongoing treatment with full-dose warfarin or its equivalent

Subjects have histologically confirmed WHO gr IV primary malignant glioma that is unresectable/multifocal. This is Phase II study where up to 41 subjects will receive up to 4 cycles of Avastin & Temozolomide. Avastin administered at 10 mg/kg every 14 days beginning a minimum of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in 28-day cycle. Patients will receive up to 4 cycles of Avastin & Temozolomide, then proceed with standard XRT. Study will use 2-stage "minimax" study design in which 21 subjects are accrued during 1st stage, with possibility that additional 20 patients accrued during 2nd stage. In initial Phase I & II trials, 4 potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, & hemorrhage. Avastin-associated adverse events in Phase III trials include congestive heart failure, GI perforations, wound healing complications, & arterial thromboembolic events. Most common toxicity associated with Temozolomide has been mild myelosuppression.

Arms

Experimental: Avastin and Temozolomide

Avastin administered at 10 mg/kg every 2 weeks beginning a minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in a 28-day cycle.

Interventions

Drug: - Avastin and Temozolomide

This is Phase II study with the combination of Avastin & Temozolomide for unresectable or multifocal WHO grade IV malignant glioma patients. Patients will receive up to 4 cycles of Avastin & Temozolomide . Avastin administered at 10 mg/kg every 14 days beginning minimum of 7 days after biopsy or 28 days after craniotomy. Temozolomide will be dosed at 200 mg/m2 daily x 5 days in 28-day cycle. Patients will have baseline MRI & repeat MRI every 4 weeks. If there is no evidence of disease progression after each cycle, or unacceptable toxicity, or as determined by investigators, patient non-compliance or patient withdraws consent to continue therapy & requests discontinuation, patients will receive up to 4 cycles of Avastin & Temozolomide, then proceed with standard XRT therapy, & future therapy after 4 cycles will be at discretion of patient & treating physicians.