Brain and Central Nervous System Tumors
Conditions
Keywords
adult glioblastoma, adult anaplastic astrocytoma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. It is not yet known which regimen of chemotherapy is more effective in treating recurrent malignant glioma. PURPOSE: Randomized phase III trial to compare the effectiveness of temozolomide alone to that of procarbazine, lomustine, and vincristine in treating patients who have recurrent malignant glioma.
Detailed description
OBJECTIVES: * Compare the efficacy of temozolomide vs procarbazine, lomustine, and vincristine, in terms of overall survival, in patients with recurrent malignant glioma. * Compare progression-free survival of patients treated with these regimens. * Compare progression-free survival at 12 weeks in patients treated with two different schedules of temozolomide. * Compare the overall survival of patients treated with two different schedules of temozolomide. * Compare toxic effects of two different schedules of temozolomide in these patients. * Compare quality of life of patients treated with these regimens. OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are randomized to 1 of 2 treatment arms. * Arm I:Patients are randomized to 1 of 2 treatment schedules: * Schedule 1: Patients receive oral temozolomide once daily on days 1-5. * Schedule 2:Patients receive oral temozolomide once daily on days 1-21. Treatment on both schedules repeats every 4 weeks for a maximum of 9 courses in the absence of disease progression or unacceptable toxicity. * Arm II:Patients receive oral lomustine and vincristine IV on day 1 and oral procarbazine on days 1-21. Treatment repeats every 6 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and at 12 and 24 weeks. Patients are followed every 12 weeks. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 500 patients (250 per treatment arm) will be accrued for this study.
Interventions
DRUGlomustine
DRUGprocarbazine hydrochloride
DRUGtemozolomide
DRUGvincristine sulfate
Sponsors
Institute of Cancer Research, United Kingdom
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed anaplastic astrocytoma, glioblastoma multiforme, or gliosarcoma * WHO grade III or IV at diagnosis or relapse * Must have undergone primary therapy including radiotherapy * Must be in first recurrence confirmed by CT scan or MRI * Evaluable disease by CT scan or MRI PATIENT CHARACTERISTICS: Age * 18 and over Performance status * WHO 0-3 Life expectancy * At least 1 month Hematopoietic * Absolute neutrophil count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 Hepatic * Total and direct bilirubin less than 1.5 times upper limit of normal (ULN) * SGOT or SGPT less than 3 times ULN * Alkaline phosphatase less than 2 times ULN Renal * BUN less than 1.5 times ULN * Creatinine less than 1.5 times ULN Other * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No other concurrent serious illness * Considered fit to receive chemotherapy PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * No prior chemotherapy for glioma Endocrine therapy * Not specified Radiotherapy * See Disease Characteristics * At least 2 months since prior radiotherapy * No prior radiosurgery, interstitial radiotherapy, or brachytherapy for glioma Surgery * Prior debulking surgery for recurrent disease allowed
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall survival | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-free survival at 12 weeks (Arm II) | — |
| Toxicity | — |
| Overall survival | — |
| Quality of life as measured by EORTC QLQ-C30 and BTM | — |
| Cost effectiveness | — |
Countries
United Kingdom
Outcome results
None listed