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

Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Glioblastoma; Gliosarcoma

Intervention: Avastin and Temozolomide (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Katherine B Peters, MD, PhD, Principal Investigator, Affiliation: Duke University Health System

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

Clinical Details

Official title: Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Response Rate

Detailed description: 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.

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Duke University Health System, Durham, North Carolina 27710, United States
Additional Information

The Preston Robert Tisch Brain Tumor Center at DUKE

Starting date: August 2007
Last updated: May 20, 2013

Page last updated: August 23, 2015

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