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

NCT00612339 | Completed Phase 2 Results DMC

• 1 other identifier: Pro00001022
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

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

Conditions

Glioblastoma; Gliosarcoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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.

  4 months

Study Arms (1)

Avastin and Temozolomide

EXPERIMENTAL

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

Interventions

Avastin and Temozolomide DRUG

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.

Also known as: Avastin - Bevacizumab, Temozolomide - Temodar

Avastin and Temozolomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Duke University: lead
• Genentech, Inc.: collaborator
• Schering-Plough: collaborator

Study Sites (1)

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at DUKE

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma; Glioma; Brain Neoplasms

Interventions

Bevacizumab; Temozolomide

Condition Hierarchy (Ancestors)

Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Katherine Peters, MD, PhD
• Organization: Duke University Medical Center

katherine.peters@duke.edu

9196846173

Study Officials

• Katherine B Peters, MD, PhD

  Duke Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2008
• First Posted: February 11, 2008
• Study Start: August 1, 2007
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 27, 2013
• Results First Posted: September 10, 2012

Record last verified: 2012-09

Locations

US (1)