Dasatinib Plus Radiation Therapy/Temozolomide in Newly-Diagnosed Glioblastoma
-To define the maximum tolerated dose (MTD) of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ) administered at 75 mg/m^2/day in patients with newly-diagnosed glioblastoma (GBM).
- To characterize the safety profile of dasatinib (Sprycel) in combination with radiotherapy (RT) and concomitant TMZ in patients with newly-diagnosed GBM.
- To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant TMZ in patients with glioblastoma after RT.
STUDY DID NOT PROGRESS TO PHASE II PORTION.
-To determine the effectiveness of dasatinib (Sprycel) with radiotherapy (RT) and 6 weeks of concomitant temozolomide (TMZ) administered at 75 mg/m^2/day followed by adjuvant temozolomide with concurrent dasatinib in patients with newly-diagnosed glioblastoma (GBM) as measured by overall survival.
- To determine the efficacy of this treatment as measured by radiographic response (RR), progression-free survival (PFS) and time to progression (TTP).
- To characterize the safety profile of dasatinib (Sprycel) in combination with RT and concomitant TMZ in patients with newly-diagnosed GBM.
- To characterize the safety profile of dasatinib (Sprycel) in combination with adjuvant TMZ in patients with GBM after RT.
-To correlate tumor genotype, tumor expression of dasatinib target proteins (e.g. Src, EphA2, c-kit and PDGFR), and PTEN levels with response to therapy with dasatinib and temozolomide.
Radiation: RT (Radiotherapy)
Drug: TMZ (Temozolomide)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I/II Trial of Dasatinib (Sprycel) With Radiation Therapy and Concomitant and Adjuvant Temozolomide in Patients With Newly-Diagnosed Glioblastoma|
- Maximum tolerated dose (MTD) [ Time Frame: Baseline then after each 28-day study cycle ] [ Designated as safety issue: Yes ]The MTD of dasatinib will be that dose at which fewer than one-third of participants experience dose limiting toxicity (DLT). Escalations are planned in groups of three patients, with an additional three patients to be added at the first indication of DLT.
- Overall survival (OS) [ Time Frame: Baseline till participant death or end of follow-up period, approximately 12 to 18 months (following 12 cycles of treatment) ] [ Designated as safety issue: No ]Overall survival (OS) is defined as the time from surgical diagnosis to the date of death from any cause. For participants who are still alive at the time of analysis, survival time will be censored at the last contact date.
|Study Start Date:||May 2009|
|Study Completion Date:||August 2013|
|Primary Completion Date:||August 2013 (Final data collection date for primary outcome measure)|
Experimental: Dasatinib Plus RT + TMZ
Dasatinib (Sprycel) with Radiotherapy (RT) and 6 weeks of concomitant Temozolomide (TMZ)
Starting dose of 150 mg/day administered by mouth daily on Days 1 to 28 of every 28 day cycle, beginning on the first day of RT.
Other Names:Radiation: RT (Radiotherapy)
As a part of standard of care, receive 60 Gy radiation therapy Monday-Friday for a total of 30 radiation treatments (about 6 weeks).
Other Name: Radiation TherapyDrug: TMZ (Temozolomide)
75 mg/m^2 capsules daily by mouth for up to a maximum of 7 weeks beginning first day of RT until RT end followed by 4 weeks off then 150 mg/m^2 daily on Days 1-5 of each 28 day study cycle and 200 mg/m^2 daily of subsequent cycles.
Other Name: Temodar
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00895960
|United States, Texas|
|UT MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Chair:||John De Groot, MD||UT MD Anderson Cancer Center|