Preoperative Chemoradiation for Glioblastoma

Study Overview
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Brief Summary
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Trial to determine the safety of neoadjuvant treatment with concurrent temozolomide and radiation therapy, followed by surgery and then further temozolomide.

Detailed Description
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Prior to any definitive treatment and after enrollment, the patient will undergo stereotactic biopsy of the lesion to confirm the histology of the lesion and to determine methylated methylguanine methyltransferase (MGMT) status. Standard image-guided stereotactic technique will be used. Patients will be treated with conformal radiation therapy. Temozolomide will be given from the day prior to radiation therapy through the last day of radiation therapy. 4-6 weeks after radiation therapy the patient will undergo craniotomy and maximal safe resection. Temozolomide will continue beginning 4 weeks after surgery. Imaging: MRI within 2 weeks prior to the start of the protocol. MRI at 4 weeks after chemoradiation therapy and prior to surgery. MRI within 48 hours after surgery. MRI after every 2 cycles of chemotherapy and then every 2 months until progression, up to 2 years.

Official Title
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Phase I Pilot Study of Preoperative Chemoradiation for Glioblastoma

Conditions
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Glioblastoma

Intervention / Treatment
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* Drug: Temozolomide
* Radiation: partial brain irradiation
* Procedure: stereotactic biopsy of brain tumor
* Procedure: craniotomy and tumor resection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: MRI lesions of the brain that have a high probability of being glioblastoma in a potentially resectable location in the brain (the primary study population) WHO performance status 0-2 (to allow comparison to historical controls) Adequate hematological parameters: (for safety because of neutropenia from the temozolomide) Consent can be obtained from the patient, and if the patient cannot give consent then from the medical power of attorney and if one is not assigned, then the nearest relative (required to obtain consent) Able to have MRI scans (secondary endpoint is MRI scan characteristics) Willing to have radiation treatment at a participating center (homogeneity of treatment parameters) Ages 18-80 Exclusion Criteria: Unresectable tumor Absolute neutrophil count (ANC) less than 1,200/μL Hemoglobin less than 9.0g/dL Platelet count less than 100,000/μL

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Preoperative chemoradiation<br>Stereotactic biopsy of brain tumor, then partial brain irradiation and temozolomide, followed by craniotomy and tumor resection, followed by temozolomide | Drug: Temozolomide<br>* Neoadjuvant treatment with concurrent temozolomide and radiation therapy, followed by surgery and then further temozolomide.<br>* Other names: Temodar;Radiation: partial brain irradiation<br>* Neoadjuvant treatment with concurrent temozolomide and radiation therapy, followed by surgery and then further temozolomide.<br>Procedure: stereotactic biopsy of brain tumor<br>* will be assessed for tumor type and tumor markers<br>Procedure: craniotomy and tumor resection<br>* maximal safe resection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| toxicity of treatment per Common Toxicity Criteria for Adverse Effects V3.0 | comparison of toxicity related to experimental treatment to historical local controls | up to up to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of measurement of O(6)-Methylguanine-DNA methyltransferase (MGMT) activity on stereotactic samples | determination of the feasibility of using standard MGMT activity measurement techniques on stereotactic specimens and comparison of the results with the results from the full resection. | at enrollment | 
| progression free survival |  | up to 12 months | 
| overall survival |  | up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glioblastoma, temozolomide, radiation therapy, radiotherapy, surgery, pre-operative, neoadjuvant