Ph. 2 Sorafenib + Protracted Temozolomide in Recurrent GBM
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|ClinicalTrials.gov Identifier: NCT00597493|
Recruitment Status : Completed
First Posted : January 18, 2008
Results First Posted : June 24, 2013
Last Update Posted : June 24, 2013
PURPOSE AND OBJECTIVES:
Primary Objective To evaluate the activity of Sorafenib plus protracted, daily temozolomide in patients with recurrent glioblastoma multiforme (GBM) as measured by 6-month PFS.
Secondary Objectives To evaluate the safety and toxicity of combination therapy using Sorafenib plus temozolomide; To determine the pharmacokinetics of Sorafenib when combined with temozolomide in patients on and not on concurrent EIAC medications.
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Glioblastoma Multiforme||Drug: Sorafenib and Temozolomide||Phase 2|
STUDY ACTIVITIES AND POPULATION GROUP:
This is an open-label, non-randomized, single center phase 2 trial. A treatment cycle will consist of 4 weeks of therapy.
Sorafenib will be administered at a set dose of 400 mg (2 x 200 mg tablets) twice daily, without food (at least 1 hour before or 2 hours after eating). Temozolomide will be administered at a set dose of 50 mg/m2 once daily without food (at least 1 hour before or 2 hours after eating).
Thirty-two (32) patients will be enrolled in this single-stage study.
DATA ANALYSIS AND RISK/SAFETY ISSUES:
After 16 patients with recurrent GBM are treated, an interim analysis will be conducted. If 6 or more patients have experienced unacceptable toxicity, accrual of patients in this patient group will be terminated. Otherwise, patient accrual will continue. If 9 or more of the total 32 patients experience unacceptable toxicity, the treatment regimen will be considered to have an unacceptable toxicity profile. The type I and II error rates associated with this testing are 0.053 and 0.053, respectively.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||32 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase 2 Study of Sorafenib Plus Protracted Temozolomide in Recurrent Glioblastoma Multiforme|
|Study Start Date :||September 2007|
|Primary Completion Date :||February 2009|
|Study Completion Date :||December 2010|
Experimental: Sorafenib + Temozolomide
Subjects receive 400mg of Sorafenib twice daily and 50mg/m^2 of Temozolomide once daily
Subjects continue to receive treatment until any of the following: progressive disease, unacceptable toxicity, non-compliance with study guidelines, withdrawal of patient consent, intercurrent non-cancer-related illness that prevents continuation of therapy or regular follow-up, general or specific changes in a subject's condition which render the patient unacceptable for treatment in the judgement of the investigator, or study closure
Drug: Sorafenib and Temozolomide
Temozolomide (50 mg per meter-squared of body surface area)every day by mouth in combination with sorafenib. Sorafenib will be taken by mouth twice every day. The dose of sorafenib will be 400 mg (2 x 200mg tablets).
- 6 Month Progression Free Survival (PFS) [ Time Frame: 6 months ]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.
- Safety and Toxicity of Combination [ Time Frame: 16 months ]Number of participants experiencing a toxicity of at least grade 3 that was deemed possibly, probably, or definitely related to the treatment.
- Pharmacokinetics: C-max [ Time Frame: 13 months ]Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. C-max refers to maximum plasma concentration. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAED) and those who were not were analyzed separately.
- Pharmacokinetics: T-max [ Time Frame: 13 months ]Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. T-max refers to time to maximum concentration. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAED) and those who were not were analyzed separately.
- Pharmacokinetics: AUC-24 [ Time Frame: 13 months ]Blood sampling for sorafenib pharmacokinetics was performed on days 1 and 28 of cycle 1 and was obtained before and at 0.5, 1, 2, 4, 6, 8, and 24 h after the morning dose. AUC-24 refers to area under the plasma concentration-time curve from 0 to 24 hours. The pharmacokinetics of those patients taking enzyme-inducing antiepileptic drugs (EIAEDs) and those who were not were analyzed separately.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00597493
|United States, North Carolina|
|Duke University Health System|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||David A Reardon, MD||Duke University Health System|