Radiation Therapy, Temozolomide, and Irinotecan in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as temozolomide and irinotecan, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining radiation therapy with chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying how well radiation therapy, temozolomide, and irinotecan work in treating patients with newly diagnosed glioblastoma multiforme.

Detailed Description
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OBJECTIVES: Compare overall survival of patients with newly diagnosed supratentorial glioblastoma multiforme treated with radiotherapy and temozolomide followed by temozolomide and irinotecan with historical controls from the RTOG database. Determine the short- and long-term toxicity of this regimen in these patients. Determine progression-free survival of patients treated with this regimen. OUTLINE: This is a multicenter study. Chemoradiotherapy: Patients undergo radiotherapy once daily, 5 days a week, for 6 weeks. Concurrently with radiotherapy, patients receive oral temozolomide once daily, 7 days a week, for 6 weeks. Post-radiotherapy chemotherapy: Beginning 4-6 weeks after the completion of chemoradiotherapy, patients receive irinotecan IV on days 1 and 15 and oral temozolomide once daily on days 1-5. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients are followed every 2 months for 2 years and then every 6 months thereafter. PROJECTED ACCRUAL: A total of 157 patients will be accrued for this study within 11 months.

Official Title
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A Phase II Study Of Radiation Therapy Plus Low Dose Temozolomide Followed By Temozolomide Plus Irinotecan For Glioblastoma Multiforme

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: irinotecan hydrochloride
* Drug: temozolomide
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed newly diagnosed supratentorial glioblastoma multiforme by surgical biopsy or excision No gliomas graded less than glioblastoma multiforme No recurrent malignant gliomas No tumor foci below the tentorium or beyond the cranial vault Study therapy must begin ≤ 5 weeks after surgery PATIENT CHARACTERISTICS: Age 18 and over Performance status Zubrod 0-1 Life expectancy At least 8 weeks Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Hemoglobin ≥ 10 g/dL* Hematocrit ≥ 30%* NOTE: *Transfusion allowed Hepatic Bilirubin ≤ 0.5 mg/dL ALT or AST ≤ 2 times upper limit of normal Renal Creatinine ≤ 1.5 mg/dL BUN ≤ 25 mg/dL Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective double-barrier contraception during and for 2 months after study participation No AIDS No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix or bladder No other major medical illness or psychiatric impairment that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No concurrent sargramostim (GM-CSF) Chemotherapy No other concurrent chemotherapy Endocrine therapy Concurrent steroid therapy allowed provided patient is on a stable or decreasing dose for at least 2 weeks before study entry Radiotherapy No prior radiotherapy to the head or neck resulting in overlap of radiotherapy fields Prior radiotherapy for stage T1 glottic cancer allowed Surgery See Disease Characteristics Recovered from prior surgery Other No enzyme-inducing antiepileptic drugs within 14 days before the initiation of irinotecan Concurrent non-enzyme-inducing antiepileptic drugs 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RT with chemotherapy + post-radiation chemotherapy<br>Radiation therapy (RT) with concurrent chemotherapy + post-radiation chemotherapy | Drug: irinotecan hydrochloride<br> <br> Drug: temozolomide<br> <br> Procedure: adjuvant therapy<br> <br> Radiation: radiation therapy<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | From registration to date of death or last follow-up. Analysis occurs after all patients have been potentially followed for 18 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | From randomization to date of progression, death, or last follow-up. Analysis occurs at the same time as the primary outcome analysis. | 

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