Nelfinavir Mesylate, Radiation Therapy, and Temozolomide in Treating Patients With Glioblastoma Multiforme

Study Overview
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Brief Summary
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RATIONALE: Nelfinavir mesylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving nelfinavir mesylate together with radiation therapy and temozolomide may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of nelfinavir mesylate when given together with radiation therapy and temozolomide in treating patients with glioblastoma multiforme.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of nelfinavir mesylate when given concurrently with radiotherapy and temozolomide followed by temozolomide alone in patients with glioblastoma multiforme. Determine the safety and dose-limiting toxicities of this regimen in these patients. Secondary Determine the progression-free survival (PFS) and overall survival (OS) of patients treated with this regimen. Compare the observed median values of PFS and OS obtained in this study to the historical median values of 6.9 months and 14.6 months, respectively. OUTLINE: This is a dose-escalation study of nelfinavir mesylate. Patients receive oral nelfinavir mesylate twice daily beginning 7-10 days before the initiation of chemoradiotherapy and continuing until the completion of chemoradiotherapy. Patients undergo radiotherapy once daily 5 days a week and receive concurrent oral temozolomide once daily for 6 weeks. Beginning 4 weeks after completion of nelfinavir mesylate and chemoradiotherapy, patients receive oral temozolomide alone once daily on days 1-5. Treatment with temozolomide repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed periodically.

Official Title
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A Phase I Trial of the Protease Inhibitor Nelfinavir and Concurrent Radiation and Temozolomide in Patients With WHO Grade IV Glioma

Conditions
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Brain and Central Nervous System Tumors

Intervention / Treatment
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* Drug: nelfinavir mesylate
* Drug: temozolomide
* Procedure: adjuvant therapy
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed WHO grade IV supratentorial astrocytoma (glioblastoma multiforme) Newly diagnosed disease Has undergone maximal surgical resection PATIENT CHARACTERISTICS: ECOG performance status 0-2 ANC ≥ 1,500/mm^3 Platelet count ≥ 100,000/mm^3 Serum creatinine < 1.5 times upper limit of normal (ULN) AST or ALT < 2 times ULN Serum bilirubin < 1.5 mg/dL No known HIV infection Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior cranial radiotherapy More than 30 days since prior investigational agents No other concurrent investigational agents No concurrent use of any of the following drugs: Antiarrhythmics (i.e., amiodarone or quinidine) Antimycobacterials (i.e., rifampin) Ergot derivatives (i.e., dihydroergotamine, ergonovine, ergotamine, or methylergonovine) Herbal products (i.e., St. John's wort) HMG-CoA reductase inhibitors (i.e., lovastatin or simvastatin) Neuroleptics (i.e., pimozide) Sedatives and/or hypnotics (i.e., midazolam or triazolam) Concurrent corticosteroids allowed provided dose has been stable or decreasing for ≥ 14 days prior to study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Single arm<br>NFV-RT-Tem | Drug: nelfinavir mesylate<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 |
| --- | --- | --- |
| Maximum tolerated dose of nelfinavir mesylate |  | 90 days | 
| Dose-limiting toxicities as assessed by NCI CTC v3.0 |  | 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival |  | One year | 
| Overall survival |  | 5 years | 

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