Bi-weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
Michael Badruddoja, MD, Center for Neurosciences, Tucson
ClinicalTrials.gov Identifier:
NCT00883298
First received: April 16, 2009
Last updated: April 1, 2014
Last verified: April 2014
  Purpose

Primary objective - to determine the 6-month progression free survival (PFS) of adult patients with recurrent glioblastoma multiforme/gliosarcoma treated with bi-weekly temozolomide plus (Avastin) bevacizumab.

Secondary objectives - to determine radiographic response including specialized MRI sequences, safety and overall survival of adult patients with with recurrent glioblastoma multiforme/gliosarcoma treated with bi-weekly temozolomide plus bevacizumab (Avastin). Additionally, tumor DNA (MGMT) analysis as it relates to survival will be evaluated.


Condition Intervention Phase
Recurrent Glioblastoma Multiforme
Recurrent Gliosarcoma
Drug: temozolomide and bevacizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Bi-Weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme

Resource links provided by NLM:


Further study details as provided by Center for Neurosciences, Tucson:

Primary Outcome Measures:
  • 6-month progression-free survival. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Radiographic response (Gd-MRI) including specialized MRI sequences (T2/FLAIR). [ Time Frame: every eight weeks ] [ Designated as safety issue: No ]
  • Incidence and severity of toxicity. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Tumor DNA (MGMT) analysis as it relates to survival. [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: April 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: temozolomide and bevacizumab
    oral temozolomide 100 mg/m2 days 1-5 & 15-19 every 28-day cycle plus intravenous bevacizumab 10 mg/kg days 1 & 5 every 28-day cycle
    Other Names:
    • Temodar
    • Avastin
Detailed Description:

This is a phase II study of the combination of Avastin and temozolomide for patients with recurrent glioblastoma multiforme. Avastin is administered intravenously at a dose of 10 mg/kg on days 1 and 15 every 28 days and temozolomide is administered at a dose of 100 mg/m2 on days 1-5 and 15-19 every 28 days (one cycle). Patients will have a baseline MRI, an MRI scan after the first cycle and every other cycle after that. If there is no evidence of disease progression or unacceptable toxicity, patients will receive one year of therapy. If there is evidence of added benefit (eg: tumor regression), patients can stay on treatment longer than one year, per investigator discretion.

  Eligibility

Ages Eligible for Study:   18 Years to 83 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must have histologically confirmed diagnosis of a glioblastoma multiforme/gliosarcoma and:

  • Must have completed at least 2 cycles of adjuvant chemotherapy
  • Age > 18 years
  • Karnofsky > 60%
  • Hematocrit > 29%, ANC > 1,500 cells/dl, platelets > 125,000 cells/dl
  • Serum creatinine < 1.5 mg/dl, BUN < 25 mg/dl, serum SGOT and bilirubin < 1.5 times upper limit of normal
  • If on corticosteroids, must be on a stable dose for 1 week prior to entry; if clinically possible, the dose should not be escalated over entry dose level
  • Signed informed consent approved by the Institutional Review Board prior to study entry
  • If sexually active, will take contraceptive measures for the duration of the treatments

Exclusion Criteria:

  • Prior toxicity grade ≥ 3 with TMZ
  • Prior treatment with bevacizumab
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control
  • Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
  • Acute or chronic liver disease (i.e., hepatitis, cirrhosis)
  • Confirmed diagnosis of HIV infection
  • Have received investigational drugs less than 4 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy
  • Have received chemotherapy within 2 weeks prior (6 weeks for nitrosourea) to entry on this study, or who have not recovered from the toxic effects of such therapy
  • Have received biologic, immunotherapeutic or cytostatic agents within 1 week prior to entry on this study or who have not recovered from the toxic effects of such therapy
  • Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant
  • Have received radiation therapy within 2 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy.
  • Surgical resection of brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy
  • Have had any surgery other than resection of a brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy
  • Unwilling to or unable to comply with the protocol
  • Evidence of tumor progression within on immediate post radiation brain imaging
  • Have not received at least 2 cycles of adjuvant chemotherapy
  • Life expectancy of less than 12 weeks
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study

Bevacizumab-Specific Exclusions:

  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
  • History of myocardial infarction or unstable angina within 6 months
  • History of stroke or transient ischemic attack within 6 months
  • Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
  • Serious, non-healing wound, active ulcer, or untreated bone fracture.
  • Proteinuria as demonstrated by a UPC ratio greater than or equal to 1.0 at screening
  • Known hypersensitivity to any component of bevacizumab
  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: NCT00883298

Locations
United States, Arizona
Center for Neurosciences
Tucson, Arizona, United States, 85718
Sponsors and Collaborators
Center for Neurosciences, Tucson
Genentech
Investigators
Principal Investigator: Michael A. Badurddoja, MD Center for Neurosciences
  More Information

No publications provided

Responsible Party: Michael Badruddoja, MD, Neurologist, NeuroOncologist, Center for Neurosciences, Tucson
ClinicalTrials.gov Identifier: NCT00883298     History of Changes
Other Study ID Numbers: AVF4514s
Study First Received: April 16, 2009
Last Updated: April 1, 2014
Health Authority: USA: Institutional Review Board

Keywords provided by Center for Neurosciences, Tucson:
temozolomide
bevacizumab
Temodar
Avastin
glioblastoma multiforme
gliosarcoma
glioma
GBM
brain tumor

Additional relevant MeSH terms:
Glioblastoma
Gliosarcoma
Astrocytoma
Glioma
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 July 29, 2014