Temozolomide + Everolimus in Newly Diagnosed, Recurrent, or Progressive Malignant Glioblastoma Multiforme
- Conditions
- Brain and Central Nervous System Tumors
- Registration Number
- NCT00387400
- Lead Sponsor
- NCIC Clinical Trials Group
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving temozolomide together with everolimus may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with temozolomide in treating patients with newly diagnosed, recurrent, or progressive malignant glioblastoma multiforme.
- Detailed Description
OBJECTIVES:
Primary
* Determine the maximum tolerated dose(s) and the recommended phase II dose(s) of everolimus when administered with standard-dose temozolomide in patients with newly diagnosed, recurrent, or progressive glioblastoma multiforme.
* Determine the toxicity of this regimen in these patients.
Secondary
* Determine the efficacy of this regimen in patients with measurable disease at baseline.
* Identify correlates of activity by molecular study of paraffin-embedded tumor samples from these patients.
* Determine the pharmacokinetics of this regimen in these patients.
OUTLINE: This is a nonrandomized, nonblinded, parallel-group, multicenter, dose-escalation study of everolimus. Patients are stratified according to concurrent use of enzyme-inducing antiepileptic drugs (yes vs no).
Patients receive oral temozolomide once daily on days 2-5 in course 1 and on days 1-5 in all subsequent courses. Patients also receive oral everolimus once daily on days 1-28. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients with newly diagnosed disease receive up to 6 courses of treatment. Patients with recurrent disease who achieve a response (partial or complete response) or stable disease may continue treatment until disease progression or unacceptable toxicity.
Cohorts of 3-6 patients per stratum receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during the first course of therapy. Once the MTD is determined, an additional 6 patients are treated at the MTD.
Patients' archival diagnostic tumor tissue is evaluated during study for correlative molecular studies (by immunohistochemical staining) of mammalian target of rapamycin inhibition status (mTOR activity) and pretreatment molecular markers. Blood samples are taken periodically during course 1 for pharmacokinetic studies.
After completion of study therapy, patients are followed at 4 weeks. Patients with stable or responding disease are then followed every 3 months until relapse or progression.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Primary Outcome Measures
Name Time Method Safety and tolerability of everolimus as measured by NCI CTCAE v3.0 from the time of the first treatment
- Secondary Outcome Measures
Name Time Method Correlation of clinical outcome with pretreatment tumor tissue molecular markers as measured by molecular studies of paraffin-embedded tumor samples 4 years Assessed at study completion
Pharmacokinetics of everolimus during course 1 during course 1 Response as measured by CT scan and/or brain MRI at baseline and after every other course and clinical neurologic assessment at baseline and after every course after every other course
Trial Locations
- Locations (9)
McGill University - Dept. Oncology
🇨🇦Montreal, Quebec, Canada
Tom Baker Cancer Centre
🇨🇦Calgary, Alberta, Canada
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
BCCA - Vancouver Cancer Centre
🇨🇦Vancouver, British Columbia, Canada
CHUM - Hopital Notre-Dame
🇨🇦Montreal, Quebec, Canada
BCCA - Cancer Centre for the Southern Interior
🇨🇦Kelowna, British Columbia, Canada
QEII Health Sciences Center
🇨🇦Halifax, Nova Scotia, Canada
London Regional Cancer Program
🇨🇦London, Ontario, Canada
Univ. Health Network-Princess Margaret Hospital
🇨🇦Toronto, Ontario, Canada