Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

This study has been completed.
Sponsor:
Collaborators:
Genentech
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
  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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ 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).]


Secondary Outcome Measures:
  • 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


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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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
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
Study First Received: July 13, 2007
Results First Received: February 6, 2013
Last Updated: May 17, 2013
Health Authority: United States: Institutional Review Board

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
Temozolomide
Dacarbazine
Bevacizumab
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014