Irinotecan Plus Radiation Therapy Followed By Chemotherapy in Treating Patients With Glioblastoma Multiforme
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Irinotecan may make the tumor cells more sensitive to radiation therapy.
PURPOSE: This phase I/II trial is studying the side effects of irinotecan given together with radiation therapy followed by irinotecan and carmustine and to see how well it works in treating patients with newly-diagnosed glioblastoma multiforme.
Brain and Central Nervous System Tumors
Drug: irinotecan hydrochloride
Procedure: adjuvant therapy
Radiation: radiation therapy
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Pilot And Phase II Trial Of Irinotecan And Radiation Followed By Irinotecan And BCNU In Glioblastoma Multiforme Patients|
- Survival at 52 weeks [ Designated as safety issue: No ]
|Study Start Date:||July 2002|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
- Determine the safety of adjuvant irinotecan when administered concurrently with radiotherapy in patients with newly diagnosed glioblastoma multiforme.
- Determine survival of patients treated with this regimen followed by irinotecan and carmustine.
- Assess the toxic effects of this regimen in these patients.
- Determine whether the dose of irinotecan chosen produces radiosensitizing plasma concentrations of SN-38 in these patients.
- Assess individual variation in responses (toxicity and/or activity), pharmacokinetic parameters, and/or biological correlates due to genetic differences in enzymes involved in transport, metabolism, and/or mechanism of action of irinotecan in these patients treated with this regimen.
OUTLINE: This is a pilot, dose-escalation study of irinotecan. Patients are stratified according to receipt of concurrent enzyme-inducing anticonvulsants (EIACs) (yes vs no).
- Phase I (closed to accrual as of 3/5/2005): Patients receive carmustine IV over 2 hours on day 1 of courses 2-5 and irinotecan IV over 90 minutes (beginning immediately after carmustine infusion) on days 1, 8, 22, and 29 of courses 1-5. Patients also undergo radiotherapy 5 days a week for 6 weeks concurrently with course 1 only. Treatment repeats every 6 weeks for 5 courses in the absence of unacceptable toxicity.
Cohorts of 6 patients receive escalating doses of irinotecan until the recommended dose for phase II is determined. The recommended dose for phase II is defined as the dose at which no more than 2 of 6 patients experience dose-limiting toxicity.
- Phase II (patients receiving concurrent EIACs or non-EIACs open to accrual as of 3/5/2005): Patients receive irinotecan at the recommended dose, carmustine, and cranial irradiation as in phase I.
Patients with disease progression are followed every 3 months for 5 years and then annually for up to 10 years.
Patients taken off study for reasons other than disease progression are followed every 3 months for 1 year, every 6 months for 4 years, and then annually for 5 years.
PROJECTED ACCRUAL: A total of 12-48 patients (6-24 per stratum) will be accrued for phase I within 2-4 months (phase I closed to accrual as of 3/5/2005). A total of 93 patients will be accrued for phase II (open to accrual for patients receiving concurrent enzyme-inducing anticonvulsants [EIACs] or non-EIACs as of 3/5/2005).
Please refer to this study by its ClinicalTrials.gov identifier: NCT00027612
|Study Chair:||Kurt A. Jaeckle, MD||Mayo Clinic|