Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma
Brief summary
RATIONALE: Thalidomide may stop the growth of glioblastoma multiforme by stopping blood flow to the tumor. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining thalidomide with irinotecan may kill any tumor cells remaining after radiation therapy. PURPOSE: Phase II trial to study the effectiveness of combining thalidomide with irinotecan in treating patients who have glioblastoma multiforme that has been treated with radiation therapy.
Detailed description
OBJECTIVES: * Determine the response rate of patients with glioblastoma multiforme treated with thalidomide and irinotecan after radiotherapy. * Determine the preliminary efficacy of this regimen in these patients. * Determine the disease-free survival and overall survival of patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Assess the quality of life of patients treated with this regimen. OUTLINE: Beginning 2-4 weeks after completion of radiotherapy, patients receive irinotecan IV over 90 minutes on day 1. Patients also receive oral thalidomide daily. Treatment repeats every 21 days for at least 3 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, 1 week after the first course, prior to all subsequent courses, and then after course 6. Patients are followed for 5 years. PROJECTED ACCRUAL: A total of 9-24 patients will be accrued for this study.
Interventions
DRUGirinotecan hydrochloride
350 or 700 mg/m2 IV every 3 weeks
DRUGthalidomide
400mg/day oral
Sponsors
National Cancer Institute (NCI)
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed glioblastoma multiforme (GBM) * Recurrent disease allowed * Evaluable disease on contrast-enhanced MRI * Prior external beam radiotherapy required PATIENT CHARACTERISTICS: Age: * 18 and over Performance status: * Karnofsky 60-100% Life expectancy: * Not specified Hematopoietic: * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic: * Bilirubin no greater than 1.5 times upper limit of normal (ULN) * AST or ALT no greater than 5 times ULN Renal: * Creatinine no greater than 1.5 times ULN OR * Creatinine clearance at least 60 mL/min Cardiovascular: * No significant cardiac disease * No uncontrolled high blood pressure * No unstable angina * No congestive heart failure * No myocardial infarction within the past 3 months * No serious cardiac arrhythmias Gastrointestinal: * Able to take oral medication * No gastrointestinal abnormalities * No requirement for IV alimentation * No active peptic ulcer disease Other: * No active infection * No serious uncontrolled medical disorder * No dementia or significantly altered mental status that would preclude study * No known hypersensitivity to irinotecan or thalidomide * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use 2 forms of effective contraception, including 1 highly effective method, at least 1 month before, during, and for 1 month after study PRIOR CONCURRENT THERAPY: Biologic therapy: * No prior thalidomide Chemotherapy: * No prior irinotecan * At least 4 weeks since other prior chemotherapy (and demonstrated evidence of disease progression or relapse) Endocrine therapy: * Concurrent corticosteroids allowed if on a stable or decreasing dose for at least 1 week prior to study * No concurrent hormonal therapy for GBM Radiotherapy: * See Disease Characteristics * No concurrent radiotherapy for GBM Surgery: * No prior surgical procedures affecting absorption Other: * No other concurrent anticancer investigational agents for GBM * No concurrent cytochrome P450 inhibitors, including the following: * Nefazodone * Fluvoxamine * Fluoxetine * Sertraline * Paroxetine * Venlafaxine * Ketoconazole * Itraconazole * Fluconazole * Cimetadine * Clarithromycin * Diltiazem * Erythromycin * Protease inhibitors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response | 2 years | To evaluate the response rate and hence preliminary efficacy of Irinotecan and Thalidomide following radiotherapy in the treatment of newly diagnosed or relapsed glioblastoma multiforme. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Toxicity / QOL / Survival | 2 years | To evaluate 1) toxicity 2) quality of life 3) disease free survival and 4) overall survival of patients treated with this combination. |
Countries
United States
Outcome results
None listed