Clinical Trial: Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Avastin in Combination With Radiation and Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma Multiformes and Gliosarcomas

Brief Summary:

Primary objective: To use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection.

Secondary objective: To determine the progression-free survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.

Exploratory Objective: To explore the relationship between biomarkers and outcome (overall survival and progression-free survival) among patients with grade IV malignant glioma treated with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.

To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.


Detailed Summary: The standard of care for grade IV gliomas is radiation therapy with daily temozolomide, followed by 6 months of temozolomide. The majority of patients progress and die of their tumor. Many glioma patients are resistant to temozolomide because the tumors have high O(6)-methylguanine-DNA methyltransferase (MGMT), conferring resistance. Irinotecan is synergistic with temozolomide, and the combination may overcome high MGMT. Vascular endothelial growth factor (VEGF) is present on the cell surface and around malignant gliomas. It appears that the presence of vascular endothelial growth factor is a prognostic growth factor with more VEGF expression correlating with a poor prognosis. Monoclonal antibodies to VEGF have inhibited growth of malignant gliomas in a mouse xenograft. Avastin is a humanized monoclonal immunoglobulin G (IGG) 1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor. The combination of Avastin and irinotecan was safe and demonstrated high activity against recurrent malignant gliomas. The combination of Avastin, temozolomide, and irinotecan as the initial therapy may maximize the chance for long-term survival. There are other studies completed or ongoing for newly diagnosed glioblastoma (GBM) patients, including a Radiation Therapy Oncology Group (RTOG) study that added irinotecan to temozolomide following standard radiation therapy and temozolomide, and a University of California, Los Angeles (UCLA) study that added Avastin to standard radiation therapy and temozolomide followed by Avastin and temozolomide.
Sponsor: Duke University

Current Primary Outcome: 16-month Overall Survival (OS) [ Time Frame: 16 months ]

Percentage of participants surviving sixteen months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of death due to any cause.


Original Primary Outcome: Overall survival [ Time Frame: 12 months ]

Current Secondary Outcome:

  • 12-month Progression-free Survival (PFS) [ Time Frame: 12 months ]
    Percentage of participants surviving twelve 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.
  • Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage [ Time Frame: 55 months ]
    Number of times a CNS hemorrhage or systemic hemorrhage was experienced
  • Number of Patients Experiencing a Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity [ Time Frame: 55 months ]
    Number of times a grade ≥ 4 hematologic or grade ≥ 3 non-hematologic toxicity was experienced


Original Secondary Outcome:

  • Progression-free survival and radiologic response [ Time Frame: 12 months ]
  • Incidence and severity of CNS hemorrhage and systemic hemorrhage. Incidence of grade > 4 hematologic and > grade 3 non-hematologic toxicities [ Time Frame: 12 months ]


Information By: Duke University

Dates:
Date Received: January 10, 2008
Date Started: July 2007
Date Completion:
Last Updated: April 22, 2014
Last Verified: April 2014