Avastin in Combo w Temozolomide for Unresectable or Multifocal GBMs and Gliosarcomas - Full Text View

Sponsors and Collaborators:	Duke University Genentech Schering-Plough
Information provided by:	Duke University
ClinicalTrials.gov Identifier:	NCT00612339

Purpose

Primary objective- To determine efficacy of Avastin, 10 mg/kg Q O wk in combo w standard 5-day temo in terms of response rate & progression-free survival.

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

Condition	Intervention	Phase
Glioblastoma Gliosarcoma	Drug: Avastin, & temozolomide	Phase II

Drug Information available for: Temozolomide Bevacizumab BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Efficacy Study
Official Title:	Avastin in Combination With Temozolomide for Unresectable or Multifocal Glioblastoma Multiformes and Gliosarcomas

Further study details as provided by Duke University:

Primary Outcome Measures:

Response rate [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Progression-free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
Incidence & severity of CNS hemorrhage & systemic hemorrhage. Incidence of > gr4 hematologic & > gr3 non-hematologic toxicities [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	41
Study Start Date:	August 2007
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	August 2008 (Final data collection date for primary outcome measure)

Intervention Details:

This is ph II study with combo of Avastin & Temozolomide for unresectable or multifocal WHO grade IV malignant glioma pts. Pts 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. Pts 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, pt non-compliance or pt withdraws consent to continue therapy & requests discontinuation, pts 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 pt & treating physicians.

Detailed Description:

Subjects have histologically confirmed WHO gr IV primary malignant glioma that is unresectable/multifocal. This is ph 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 mini of 7 days after biopsy/28 days after craniotomy. Temozolomide dosed at 200 mg/m2 daily for 5 days in 28-day cycle. Pts will receive up to 4 cycles of Avastin & Temozolomide , then proceed w standard XRT. Study will use 2-stage "minimax" study design in which 21 subjects are accrued during 1st stage, w possibility that additional 20 pts accrued during 2nd stage. In initial Ph I & II trials, 4 potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, & hemorrhage. Avastin-associated adverse events in ph III trials include congestive heart failure, GI perforations, wound healing complications, & arterial thromboembolic events. Most common toxicity associated w temo 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:

Pts have histologically confirmed diagnosis of WHO gr IV primary malignant glioma. Pts will be unresectable or have multifocal disease.

Age ≥ 18yrs & life expectancy of >12 wks
Evidence of measurable primary CNS neoplasm on contrast enhanced MRI.
Interval of <1 wk between prior biopsy/4 wks from surgical resection & enrollment on protocol
Karnofsky ≥60 percent
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 pts on corticosteroids, they must have been on stable dose for 1wk prior to entry, if clinically possible, & dose should not be escalated over entry dose level
Signed informed consent approved by IRB prior to pt entry
No evidence of > gr1 CNS hemorrhage on baseline MRI/CT scan
If sexually active, pts 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 gr of tumor
Evidence of > gr1 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 Gr II / > congestive heart failure
History of myocardial infarction/unstable angina < 6mths prior to study enrollment
History of stroke/transient ischemic attack < 6mths 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 mths prior to study enrollment
Serious, non-healing wound, ulcer, /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 w full-dose warfarin/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:

James J Vredenburgh, MD

Duke University Health System

More Information

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

Responsible Party:	Duke University Health System ( James J. Vredenburgh )
Study ID Numbers:	00001022
Study First Received:	January 29, 2008
Last Updated:	December 26, 2008
ClinicalTrials.gov Identifier:	NCT00612339
Health Authority:	United States: Institutional Review Board

Keywords provided by Duke University:

Gliosarcoma
Glioma
Temozolomide
Temodar
Avastin
Bevacizumab

GBM
Multifocal GBM
Brain tumor
Unresectable GBM
Glioblastoma multiforme

Study placed in the following topic categories:

Glioblastoma
Dacarbazine
Astrocytoma
Bevacizumab
Temozolomide
Brain Neoplasms
Neuroectodermal Tumors

Glioblastoma multiforme
Neoplasms, Germ Cell and Embryonal
Neuroepithelioma
Glioma
Gliosarcoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Angiogenesis Inhibitors
Pharmacologic Actions

Neoplasms
Therapeutic Uses
Growth Inhibitors
Antineoplastic Agents, Alkylating
Angiogenesis Modulating Agents
Neoplasms, Neuroepithelial
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009