Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas

• Status: Completed
• Trial end date: 2012-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective- To determine efficacy of Avastin, 10 mg/kg every other week, in combination with standard 5-day temozolomide in terms of response rate.

Secondary objective- To determine safety of Avastin & Temozolomide in unresectable glioblastoma patients

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

Details

• Lead Sponsor: Duke University
• Collaborators: Genentech, Inc.; Schering-Plough
• Treatments: Bevacizumab; Dacarbazine; Temozolomide

Criteria

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