Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

This study has been completed.
Sponsor:
Collaborators:
Genentech, Inc.
Schering-Plough
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00501891
First received: July 13, 2007
Last updated: May 17, 2013
Last verified: March 2013

July 13, 2007
May 17, 2013
July 2007
December 2007   (final data collection date for primary outcome measure)
6-Month Progression-free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
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).]
Progression-free survival [ Time Frame: Monthly ]
Complete list of historical versions of study NCT00501891 on ClinicalTrials.gov Archive Site
  • Response Rate [ Time Frame: 27 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Number of participants experiencing a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity
Response rate [ Time Frame: Every 8 weeks ]
Not Provided
Not Provided
 
Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma
A Phase II Study of Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

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.

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.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Glioblastoma Multiforme
  • 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
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.
Interventions:
  • Drug: Bevacizumab
  • Drug: Metronomic Temozolomide
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
32
November 2009
December 2007   (final data collection date for primary outcome measure)

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)
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00501891
Pro00000404, AVF3821s, P04860
Yes
Duke University
Duke University
  • Genentech, Inc.
  • Schering-Plough
Principal Investigator: Annick Desjardins, MD Duke University Health System
Duke University
March 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP