Radiation Therapy and Temozolomide Followed by Temozolomide and Poly ICLC in Treating Patients With Newly Diagnosed GBM

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, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as poly ICLC, may stimulate the immune system in different ways and stop tumor cells from growing. Giving poly ICLC after radiation therapy and temozolomide may stop any remaining tumor cells from growing. PURPOSE: This phase II trial is studying how well giving radiation therapy together with temozolomide followed by temozolomide and poly ICLC works in treating patients with newly diagnosed glioblastoma multiforme.

Detailed Description
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OBJECTIVES: Primary Evaluate the safety and efficacy of radiation plus low-dose temozolomide followed by adjuvant temozolomide and intramuscular poly ICLC for adult patients with newly diagnosed glioblastoma multiforme. Secondary Estimate the frequency of toxicity associated with this treatment regimen. OUTLINE: This is an open-label, multicenter study. Induction chemoradiotherapy: Patients undergo radiotherapy once daily, 5 days a week, for 6 weeks. During the same 6 weeks, patients also receive oral temozolomide once daily. Four weeks later, patients are evaluated for disease progression. Patients with progressive disease are removed from the study. Patients with no progressive disease proceed to maintenance therapy. Maintenance therapy: Patients receive oral temozolomide once daily on days 1-5 (week 1). Patients also receive poly ICLC intramuscularly three times a week in weeks 2-8. Courses repeat every 9 weeks in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed every 2 months for survival. PROJECTED ACCRUAL: A total of 96 patients will be accrued for this study.

Official Title
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A Phase II Trial of Radiation Plus Temozolomide Followed by Adjuvant Temozolomide and Poly-ICLC in Patients With Newly Diagnosed Glioblastoma Multiforme

Conditions
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Glioblastoma Multiforme

Intervention / Treatment
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* Drug: poly ICLC
* Drug: temozolomide
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) by biopsy or resection within the past 3 months PATIENT CHARACTERISTICS: Karnofsky performance status ≥ 60% Absolute neutrophil count ≥ 1500/mm^3 Platelet count ≥ 100,000/mm^3 Bilirubin ≤ 1.5 mg/dL Transaminases ≤ 4 times above the upper limits of the institutional normal Creatinine ≤ 1.7 mg/dL Not pregnant or breast-feeding Patients must agree to follow acceptable birth control methods to avoid conception Negative pregnancy test Patients must have a Mini Mental State Exam score of ≥ 15 No serious concurrent infection or medical illness which would jeopardize the ability of the patient to receive the treatment outlined in this protocol with reasonable safety Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin Patients who have been free of disease (any prior malignancy) for ≥ five years are eligible for this study Patients requiring ongoing therapy for psychoses with antipsychotic medications at the time of enrollment will be ineligible PRIOR CONCURRENT THERAPY: Patients must not have received prior radiation therapy, chemotherapy, immunotherapy or therapy with biologic agent (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor Prior glucocorticoid therapy is allowed Patients must be willing to forego other cytotoxic and non-cytotoxic drug therapy against the tumor while being treated with poly ICLC plus temozolomide on this protocol No other concurrent therapy for their tumor (i.e., chemotherapeutics or investigational agents) Patients who have received prior Gliadel wafers are not eligible for this study No concurrent prophylactic filgrastim (G-CSF) No concurrent electron, particle, implant, or stereotactic radiosurgery boost

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: Treatment Arm<br>RT + TMZ 6wks, followed by poly ICLC, temozolomide, radiation: radiation therapy | Drug: poly ICLC<br>* 20 mcg/kg 3x each week (Maintenance cycles)<br>* Other names: Holtonol;Drug: temozolomide<br>* daily 75mg/m2 6wks concomitant therapy Wk 1 - days 1-5 150-200 mg/m2 maintenance cycles (adjuvant)<br>* Other names: Temodar;Radiation: radiation therapy<br>* RT: 60 Gy (6 weeks) concomitant therapy<br>* Other names: RT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | survival time is defined from time of histological diagnosis to death occurrence. | 30 months | 

 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