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

May 20, 2013 updated by: Duke University

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

41

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Health System

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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.
Other Names:
  • Avastin - Bevacizumab
  • Temozolomide - Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: 4 months
The proportion of subjects with complete or partial response as determined by a modification of the RANO (Response Assessment in Neuro-Oncology) criteria. A confirmation of response was not required. Complete Response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.
4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Genentech, Inc.
Schering-Plough

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (Actual)

May 1, 2012

Study Completion (Actual)

May 1, 2012

Study Registration Dates

First Submitted

January 29, 2008

First Submitted That Met QC Criteria

February 8, 2008

First Posted (Estimate)

February 11, 2008

Study Record Updates

Last Update Posted (Estimate)

May 27, 2013

Last Update Submitted That Met QC Criteria

May 20, 2013

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00001022

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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