A Study Comparing GLIADEL to Stereotactic Radiosurgery in Metastatic Brain Disease

Study Overview
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Brief Summary
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This study is being done to see if adding GLIADEL to the site where the tumor was removed works as well as just having the tumor removed with radiation treatment done within six weeks after the surgery to keep the cancer from coming back.

Detailed Description
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This study is being done to assess the efficacy of GLIADEL (a local chemotherapy) in preventing local recurrence of a metastatic brain tumor compared to stereotactic radiosurgery (SRS) after resection. 100 Adult subjects with one to four metastatic brain tumors with one tumor needing resection will be enrolled. Subjects with prior radiation, lymphoma, small cell, germ cell, unknown primary, or anaplastic thyroid diagnoses will be ineligible. Life expectancy should be greater than 3 months. Subjects will be randomized at the time of surgery to 1) GLIADEL placement at the time of resection or 2) SRS post-operatively to the resection cavity. Any other tumors (up to three) will have SRS as their primary treatment after surgery. SRS will take place within 6 weeks from surgery. Subjects will be evaluated pre-operatively with MRI brain and neuropsychological testing and will have immediate post-op MRI for extent of resection (EOR) determination. Subjects will have SRS to the resection cavity if no GLIADEL was placed and all will have SRS to any other lesions. They will be followed at set intervals to evaluate for local recurrence and neurocognitive changes. The genome of the metastatic brain tumor will be compared to their primary and germline for identification of alterations.

Official Title
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A Randomized Trial Evaluating GLIADEL Compared to Stereotactic Radiosurgery in Subjects With Metastatic Brain Disease

Conditions
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Brain Tumor - Metastatic

Intervention / Treatment
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* Drug: Carmustine 7.7Mg Wafer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older (Nebraska is 19 years or older) Karnofsky Performance Score ≥ 70 RPA class I or II Known or suspected primary solid cancer with metastatic brain tumor(s) - up to four in number and up to 4 cm in size with surgical resection planned for one or two tumors. Adequate platelet count (≥ 100,000/mm3), transfusion permitted Laboratory values adequate for patient to undergo surgery, including: (transfusion permitted to reach goals) Women of childbearing potential must have a negative pregnancy test within 7 days of initiating study INR ≤ 1.3 Estimated survival time of ≥ 3 months as determined by the patient's primary oncologist. The subject is willing and able to consent to and abide by the protocol. Exclusion Criteria: Prior treatment to the area of planned resection (surgery, radiation). Prior whole brain radiation therapy. Diagnosis of lymphoma, germ cell cancer, small cell lung cancer, anaplastic thyroid cancer. Leptomeningeal disease Neurodegenerative disorder (e.g. dementia). Tumor size > 4 cm. RPA class III Inability or unwillingness to co-operate with the requirements of the protocol Any other clinically significant medical disease or condition laboratory abnormality or psychiatric illness that, in the Investigator's opinion, may interfere with protocol adherence or confound efficacy or safety assessment or a subject's ability to give informed consent. Participation in other therapeutic clinical trials Severe pulmonary, cardiac or other systemic disease, specifically: New York Heart Association > Grade 2 congestive heart failure within 6 months prior to study entry, unless asymptomatic and well controlled with medication Uncontrolled or significant cardiovascular disease, clinically significant ventricular arrhythmia, clinically significant pulmonary disease Subjects who have any other disease, either metabolic or psychological, which as per the Investigator assessment may affect the subject's compliance or place the subject at higher risk of potential treatment complications. The subject has a bleeding diathesis, or must take anticoagulants, or antiplatelet agents including NSAIDs (non-steroidal anti-inflammatory drugs), at the time of scheduled resection that cannot be stopped for surgery. Inability to obtain MRI studies.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Subjects will be randomized to either 1) the GLIADEL Arm or 2) the Standard of Care Arm (SRS post-op).
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard of Care Arm<br>The tumor will be removed surgically. Within 6 weeks after surgery, the resection will be treated with stereotactic radiosurgery (SRS). | |
| Experimental: GLIADEL Arm<br>Once the tumor has been removed, GLIADEL wafers will be applied to the resection cavity. The number of wafers used will be determined by the size of the cavity. Enough wafers should be used so that as much of the cavity is covered as possible. | Drug: Carmustine 7.7Mg Wafer<br>* GLIADEL wafers will be placed to cover tumor bed immediately after tumor removal.<br>* Other names: GLIADEL;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of GLIADEL compared to Stereotactic Radiosurgery (SRS) | The primary outcome is to evaluate the efficacy of GLIADEL local chemotherapy compared to Stereotactic Radiosurgery (SRS) in preventing local recurrence after resection of a metastatic brain tumor (local recurrence at surgical site). | 12 months |