Radiation Therapy, Temozolomide, Tamoxifen, and Carboplatin in Treating Patients With Malignant Gliomas

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Tamoxifen may make tumor cells more sensitive to radiation therapy and chemotherapy. Giving radiation therapy together with temozolomide, tamoxifen, and carboplatin may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well giving radiation therapy together with temozolomide, tamoxifen, and carboplatin works in treating patients with malignant gliomas.

Detailed Description
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OBJECTIVES: Determine the progression-free and overall survival of patients with supratentorial malignant gliomas (WHO grade III or IV) receiving radiotherapy with concurrent and adjuvant temozolomide, tamoxifen citrate, and carboplatin. Determine the acute and delayed treatment-related toxicities in these patients. Determine tumor response in patients with postoperative measurable disease. OUTLINE: This is an open-label, pilot study. Induction therapy: Patients receive oral temozolomide twice daily and oral tamoxifen citrate twice daily on days 1-42 and carboplatin IV over 60 minutes on days 1, 8, 15, 22, 29, and 36. Patients also receive radiotherapy on days 1-5 in weeks 1-6. Consolidation therapy: Beginning 4 weeks after the completion of induction therapy, patients receive temozolomide, tamoxifen citrate, and carboplatin as in induction therapy. Treatment repeats every 8 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed periodically for 5 years.

Official Title
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A Phase II Pilot Trial of Radiation Therapy With Concurrent and Adjuvant Temozolomide, Tamoxifen and Carboplatin (T2C) in the Treatment of Patients With Primary Central Nervous System Malignant Gliomas

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: carboplatin
* Drug: tamoxifen citrate
* Drug: temozolomide
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed glioblastoma multiforme and/or anaplastic astrocytoma Supratentorial tumor No well-differentiated astrocytoma or glioma with oligodendroglial component No multifocal glioma Has undergone surgery within the past 6 weeks No recurrent glioblastoma multiforme PATIENT CHARACTERISTICS: ECOG performance status 0-2 Neurological functional status 0-2 Life expectancy > 12 weeks ANC ≥ 1,200/mm³ Platelet count ≥ 100,000/mm³ Hemoglobin ≥ 9 g/dL Serum creatinine ≤ 1.5 times upper limit of normal (ULN) Blood urea nitrogen ≤ 1.5 times ULN Total and direct bilirubin ≤ 3 times ULN AST and ALT ≤ 3 times ULN Alkaline phosphatase ≤ 3 times ULN Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after study completion No other malignancies within the past 3 years, except for carcinoma in situ of the cervix or nonmelanoma skin cancer No acquired immune deficiency syndrome (AIDS) No major medical illness or psychiatric impairment that would preclude study compliance PRIOR CONCURRENT THERAPY: No prior radiotherapy to the head and neck No other concurrent therapy for the tumor

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
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: carboplatin|nan|
|Drug: tamoxifen citrate|nan|
|Drug: temozolomide|nan|
|Procedure: adjuvant therapy|nan|
|Radiation: radiation therapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  |  | 
| Overall survival |  |  | 
| Toxicity |  |  | 
| Tumor response |  |  | 

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