Carboxyamidotriazole + RT in Treating Patients Newly Diagnosed Supratentorial GBM

Study Overview
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Brief Summary
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Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells. Phase II trial to study the effectiveness of carboxyamidotriazole plus radiation therapy in treating patients who have newly diagnosed supratentorial glioblastoma multiforme.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate overall survival rate in patients administered CAI (carboxyamidotriazole) and radiation therapy to adults with newly diagnosed glioblastoma multiforme. II. To determine the toxicity of CAI when combined with cranial irradiation. III. To estimate correlations between pharmacokinetic parameters, including steady state CAI concentration, with toxicity and/or drug activity in this patient population. IV. To estimate duration of disease free progression with this treatment regime. OUTLINE: This is a multicenter study. Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival. PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study over 1.5 years.

Official Title
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Phase II Clinical and Pharmacologic Study of Radiation Therapy and CAI (Carboxy-Amido Triazole) in Adults With Newly Diagnosed Glioblastoma Multiforme

Conditions
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Adult Giant Cell Glioblastoma, Adult Glioblastoma, Adult Gliosarcoma

Intervention / Treatment
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* Radiation: radiation therapy
* Drug: carboxyamidotriazole
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically confirmed supratentorial grade IV astrocytoma (glioblastoma multiforme) Patients must have measurable or non-measurable tumor on the post operative, pretreatment MRI/CT scan (within two weeks of starting treatment) Patients must not have received prior radiation therapy, chemotherapy, hormonal therapy, immunotherapy or therapy with biologic agents (including immunotoxins, immunoconjugates, antisense, peptide receptor antagonists, interferons, interleukins, TIL, LAK or gene therapy), or hormonal therapy for their brain tumor; glucocorticoid therapy is allowed Patients must have recovered from the immediate post-operative period and be maintained on a stable steroid regimen (no increase for the last five days) Absolute neutrophil count >= 1500/mm^3 Platelets >= 100,000/mm^3 Hemoglobin concentration >= 9.0 g/dl Creatinine =< 1.7mg/dL Total bilirubin =< 1.2 mg/dl Transaminases =< 2 times above the upper limits of the institutional normal Estimated life expectancy greater than 2 months Patients must give informed consent and understand the investigational nature of this study and its potential risks and benefits Patients, if female and of childbearing potential must have a negative serum beta-hCG test and must not be breast feeding; all patients with the potential for pregnancy should be counseled and requested to follow acceptable birth control methods to avoid conception Patients must have a Karnofsky performance status of >= 60% No other serious concurrent infection or other medical illness should be present which would jeopardize the ability of the patient to receive the drug outlined in this protocol with reasonable safety Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ; patients with prior malignancies must be disease-free for >= five years Exclusion Criteria: Patients must be able to comply with prescribed medical care Prior therapy for the brain tumor (except surgery) Prior treatment with antineoplastic agents, including CAI

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: Treatment (RT and CAI)<br>Patients receive induction therapy consisting of radiotherapy once daily 5 days a week plus oral carboxyamidotriazole once daily for 6 weeks followed by carboxyamidotriazole alone daily for 4 weeks. Patients continue on oral carboxyamidotriazole once daily as maintenance therapy in the absence of disease progression or unacceptable toxicity. Patients are followed monthly for survival. Other: pharmacological study, radiation therapy | Radiation: radiation therapy<br>* Undergo radiotherapy<br>* Other names: therapy, radiation;Drug: carboxyamidotriazole<br>* Given orally<br>* Other names: carboxyaminoimidazole;Other: pharmacological study<br>* Correlative studies<br>* Other names: pharmacological studies;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival Rate | estimated period of time event assessed 30 months. event assessed from time of histological diagnosis to death | approximately 30 months | 
| Toxicity of CAI When Combined With RT | patients who experienced a grade 3 or higher event considered at least possibly related to CAI | pts were reviewed for toxicity while on treatement - median time of 2 months | 
| Correlation Between PK CAI and Toxicity in This pt Population | PK paramenters including steady state CAI concentrations with toxicity/or drug activity | during treatment |