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Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00501891
First Posted: July 16, 2007
Last Update Posted: May 27, 2013
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Genentech, Inc.
Schering-Plough
Information provided by (Responsible Party):
Duke University
  Purpose
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.

Condition Intervention Phase
Glioblastoma Multiforme Drug: Bevacizumab Drug: Metronomic Temozolomide Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • 6-Month Progression-free Survival [ Time Frame: 6 months ]
    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).]


Secondary Outcome Measures:
  • Response Rate [ Time Frame: 27 months ]
    The number of participants with complete or partial response as determined by a modification of the Macdonald criteria. 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.

  • Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage [ Time Frame: 27 months ]
    Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage

  • Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity [ Time Frame: 27 months ]
    Number of participants experiencing a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity


Enrollment: 32
Study Start Date: July 2007
Study Completion Date: November 2009
Primary Completion Date: December 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bevacizumab and Metronomic Temozolomide
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
Bevacizumab administered intravenously 10mg/kg every other week.
Other Name: Avastin
Drug: Metronomic Temozolomide
Temozolomide 50mg/m2 given orally on a daily basis.
Other Name: Temodar

Detailed Description:

This is a phase II trial of the combination of Avastin and metronomic temozolomide in recurrent WHO grade IV malignant glioma patients. Patients will receive up to 12 cycles of Avastin and temozolomide and cycles are continuous 28 days. Patients will receive daily temozolomide at a dose of 50mg/m2 and will receive Avastin every other week at a dose of 10mg/kg. Patients will be required to have a baseline MRI within 2 weeks of starting treatment and a repeat MRI every 8 weeks. A total of 32 patients will be enrolled at Duke.

Patients with recurrent malignant gliomas have a very poor prognosis, so new therapies are needed. Given the activity of metronomic temozolomide and the safety and activity of Avastin against malignant glioma, it is reasonable to study the combination in recurrent malignant glioma patients.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00501891


Locations
United States, North Carolina
Duke University Medical Center (Brain Tumor Center)
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Genentech, Inc.
Schering-Plough
Investigators
Principal Investigator: Annick Desjardins, MD Duke University Health System
  More Information

Additional Information:
Publications:
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00501891     History of Changes
Other Study ID Numbers: Pro00000404
AVF3821s
P04860
First Submitted: July 13, 2007
First Posted: July 16, 2007
Results First Submitted: February 6, 2013
Results First Posted: April 22, 2013
Last Update Posted: May 27, 2013
Last Verified: March 2013

Keywords provided by Duke University:
Glioblastoma Multiforme
Brain and Central Nervous System Tumors
Recurrent Malignant Glioma
Recurrent Glioblastoma Multiforme
Avastin
Bevacizumab
Temodar
Temozolomide

Additional relevant MeSH terms:
Glioblastoma
Glioma
Astrocytoma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bevacizumab
Temozolomide
Dacarbazine
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action