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

Primary Purpose

Glioblastoma, Gliosarcoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Avastin and Temozolomide

About this trial

This is an interventional treatment trial for Glioblastoma focused on measuring Glioma, Temozolomide, Temodar, Avastin, Bevacizumab, GBM, Gliosarcoma, Multifocal GBM, Brain tumor, Unresectable GBM, Glioblastoma multiforme

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Duke University Health System

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Avastin and Temozolomide

Arm Description

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.

Outcomes

Primary Outcome Measures

Response Rate

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT00612339

First Posted

January 29, 2008

Last Updated

May 20, 2013

Sponsor

Duke University

Collaborators

Genentech, Inc., Schering-Plough

1. Study Identification

Unique Protocol Identification Number

NCT00612339

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2012

Overall Recruitment Status

Completed

Study Start Date

August 2007 (undefined)

Primary Completion Date

May 2012 (Actual)

Study Completion Date

May 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Duke University

Collaborators

Genentech, Inc., Schering-Plough

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Glioblastoma, Gliosarcoma

Keywords

Glioma, Temozolomide, Temodar, Avastin, Bevacizumab, GBM, Gliosarcoma, Multifocal GBM, Brain tumor, Unresectable GBM, Glioblastoma multiforme

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

41 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Avastin and Temozolomide

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Avastin and Temozolomide

Other Intervention Name(s)

Avastin - Bevacizumab, Temozolomide - Temodar

Intervention Description

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.

Primary Outcome Measure Information:

Title

Response Rate

Description

Time Frame

4 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Katherine B Peters, MD, PhD

Organizational Affiliation

Duke Health

Official's Role

Principal Investigator

Facility Information:

Facility Name

Duke University Health System

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27710

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.cancer.duke.edu/btc/

Description

The Preston Robert Tisch Brain Tumor Center at DUKE

Learn more about this trial

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

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