Temozolomide Compared to Procarbazine, Lomustine, and Vincristine in Treating Patients With Recurrent Malignant Glioma

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective Randomised Trial Comparing Temozolomide With PCV In The Treatment Of Recurrent WHO Astrocytic Tumours Grades III And IV

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: lomustine
* Drug: procarbazine hydrochloride
* Drug: temozolomide
* Drug: vincristine sulfate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: lomustine|nan|
|Drug: procarbazine hydrochloride|nan|
|Drug: temozolomide|nan|
|Drug: vincristine sulfate|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult glioblastoma, adult anaplastic astrocytoma, recurrent adult brain tumor, adult giant cell glioblastoma, adult gliosarcoma