Avastin in Combination With Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas - Full Text View

Purpose

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

Condition	Intervention	Phase
Glioblastoma Gliosarcoma	Drug: Avastin and Temozolomide	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Resource links provided by NLM:

Drug Information available for: Temozolomide Bevacizumab

U.S. FDA Resources

Further study details as provided by Duke University:

Primary Outcome Measures:

Response Rate [ Time Frame: 4 months ] [ Designated as safety issue: No ]
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.

Enrollment:	41
Study Start Date:	August 2007
Study Completion Date:	May 2012
Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00612339

Locations

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

Sponsors and Collaborators

Duke University

Genentech

Schering-Plough

Investigators

Principal Investigator:

Katherine B Peters, MD, PhD

Duke University Health System

More Information

Additional Information:

The Preston Robert Tisch Brain Tumor Center at DUKE This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Duke University
ClinicalTrials.gov Identifier:	NCT00612339 History of Changes
Other Study ID Numbers:	00001022
Study First Received:	January 29, 2008
Results First Received:	August 9, 2012
Last Updated:	September 18, 2012
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:

Glioma
Temozolomide
Temodar
Avastin
Bevacizumab
GBM

Gliosarcoma
Multifocal GBM
Brain tumor
Unresectable GBM
Glioblastoma multiforme

Additional relevant MeSH terms:

Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Temozolomide
Dacarbazine

Bevacizumab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on May 23, 2013