Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

NCT00501891 | Completed Phase 2 Results DMC

• 3 other identifiers: Pro00000404AVF3821sP04860
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study of the combination of Avastin and metronomic temozolomide in recurrent malignant glioma patients. The primary objective will be to determine the efficacy of Avastin (bevacizumab) and metronomic temozolomide in malignant glioma patients. The secondary objective will be to determine the safety of Avastin, 10 mg/kg every other week, in combination with metronomic temozolomide in terms of progression-free survival.

Conditions

Glioblastoma Multiforme

Keywords

Glioblastoma Multiforme; Brain and Central Nervous System Tumors; Recurrent Malignant Glioma; Recurrent Glioblastoma Multiforme; Avastin; Bevacizumab; Temodar; Temozolomide

Outcome Measures

Primary Outcomes (1)

• 6-Month Progression-free Survival

  Percentage of participants surviving six months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause. \[Optional: Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).\]

  6 months

Secondary Outcomes (3)

• Response Rate

  27 months

• Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage

  27 months

• Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity

  27 months

Study Arms (1)

Bevacizumab and Metronomic Temozolomide

EXPERIMENTAL

Patients will receive up to 12 cycles of bevacizumab (Avastin) and metronomic temozolomide (Temodar), and each cycle is 28 days. Bevacizumab will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.

Drug: Bevacizumab; Drug: Metronomic Temozolomide

Interventions

Bevacizumab DRUG

Bevacizumab administered intravenously 10mg/kg every other week.

Also known as: Avastin

Bevacizumab and Metronomic Temozolomide

Metronomic Temozolomide DRUG

Temozolomide 50mg/m2 given orally on a daily basis.

Also known as: Temodar

Bevacizumab and Metronomic Temozolomide

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma
• Karnofsy Performance Status (KPS) \>/= 60%
• Evidence of measurable primary CNS neoplasm on contrast-enhanced MRI.
• An interval of at least 4 weeks between prior surgical resection or 1 week from a biopsy and enrollment on this protocol
• An interval of at least 4 weeks from the end of prior radiotherapy or one week from the end of a cycle of chemotherapy and enrollment on this protocol.
• No evidence of CNS hemorrhage on the baseline MRI or CT scans

You may not qualify if:

• Life expectancy \< 8 weeks
• Pregnancy or breast feeding
• Progression to metronomic temozolomide, defined as tumor progression while taking daily temozolomide or progression within 4 weeks of stopping metronomic temozolomide
• Inadequately controlled hypertension (defined as systolic blood pressure \>150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications)

Sponsors & Collaborators

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

Study Sites (1)

Duke University Medical Center (Brain Tumor Center)

Durham, North Carolina, 27710, United States

Location

Related Publications (1)

• Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE 2nd, Bailey L, Peters KB, Friedman HS, Vredenburgh JJ. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 2012 Mar 1;118(5):1302-12. doi: 10.1002/cncr.26381. Epub 2011 Jul 26.

  PMID: 21792866 RESULT

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke

MeSH Terms

Conditions

Glioblastoma; Central Nervous System Neoplasms; Glioma

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; Nervous System Neoplasms; Neoplasms by Site; 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: Annick Desjardins, MD
• Organization: The Preston Robert Tisch Brain Tumor Center at Duke

annick.desjardins@duke.edu

919-684-6173

Study Officials

• Annick Desjardins, MD

  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: July 13, 2007
• First Posted: July 16, 2007
• Study Start: July 1, 2007
• Primary Completion: December 1, 2007
• Study Completion: November 1, 2009
• Last Updated: May 27, 2013
• Results First Posted: April 22, 2013

Record last verified: 2013-03

Locations

US (1)