Carboplatin and Temozolomide (Temodar) for Recurrent and Symptomatic Residual Brain Metastases

Study Overview
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Brief Summary
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Purpose: The primary objective of this study is to determine if chemotherapy with carboplatin and temozolomide significantly affects the response rates, or size of disease, in patients with brain metastases, originating from cancer in other parts of the body, compared to patients who have already been treated with radiation. Survival, causes of death, recurrence of disease in the central nervous system, toxicity, and quality of life will all be measured as secondary objective in this study.

Detailed Description
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Rationale: Surgery and radiation are often used as treatments for brain metastases, or tumors in the brain that originate from other parts of the body. It is currently unknown whether patient survival or time to progression would experience additional benefits through the addition of chemotherapy. Previous research does appear to suggest that a chemotherapy regimen may improve outcomes of patients with brain metastases previously treated with radiation. The current study further evaluates this research question by providing patients with recurrent or symptomatic residual brain metastases with carboplatin and temozolomide, two chemotherapy agents. Temozolomide has demonstrated clinical antitumor efficacy against malignant gliomas and has been tested with some efficacy against several other types of cancer. This drug appears to have less adverse effects compared to other commonly used cancer drugs. Recent research indicates that temozolomide also has some efficacy against brain metastases. In addition, previous research indicates carboplatin's lack of severe toxicity in patients with this disease. Treatment: Study participants will be treated with carboplatin and temozolomide. Carboplatin will be administered through intravenous infusions. Temozolomide will be given through oral pills. Before these drugs are administered, study participants will undergo a pre-treatment evaluation with physical and neuropsychological examinations, neuro-imaging, laboratory tests, quality of life assessment, and other procedures. Carboplatin will be given for two consecutive days. Temozolomide will be taken by study participants daily for five consecutive days. Both of these treatment schedules will be repeated every 28 days. Several tests and exams will be given throughout the study to closely monitor patients. Study treatments will be discontinued due to disease growth or unacceptable adverse events.

Official Title
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Phase I/II Multicenter Trial of Intra-Arterial Carboplatin and Oral Temozolomide for the Treatment of Recurrent and Symptomatic Residual Brain Metastases.

Conditions
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Brain Tumor, Brain Metastases

Intervention / Treatment
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* Drug: carboplatin
* Drug: temozolomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed systemic cancer Exclusion Criteria: Pregnant Known CNS meningeal involvement with cancer

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: Temozolomide & Intra-Arterial (IA) carboplatin<br>Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin | Drug: carboplatin<br>* IA carboplatin 200 mg/m2/day for each arterial injection on days 1 and 2.<br>* Other names: CBDCA;Drug: temozolomide<br>* 150 mg/m2/day orally Days 1-5. Treatment cycles to be repeated every 4 weeks.<br>* Other names: Temodar;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide | Response was evaluated by MRI Criteria (MacDonald Criteria). The MacDonald criteria for determining tumor progression is determined through assessing the increase in size of an enhancing tumor on consecutive MRI scans and clinical assessment. Complete response occurs when there is a disappearance of all enhancing tumor on consecutive MRI scans at least one month apart. Partial response occurs at a >50% reduction in size of enhancing tumor on consecutive MRI scans at least one month apart. Progressive disease occurs when there is a >25% increase in size of enhancing tumor on consecutive MRI scans. Stable disease occurs in all remaining situations. | up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analyze Patients Time to Progression | Responses to treatment was determined by comparing new enhanced MRI scans with those obtained at the previous evaluation (i.e., 2 treatment cycles ago) or with the pre-IA chemotherapy baseline scan, if it is the first follow-up MRI scan during treatment. MRI is the neuro-imaging modality of choice, since it is more accurate than CT for small tumors, multiple tumors, and tumors in the posterior fossa.58 The methodology used (techniques and equipment) must be identical for all scans. Lesions should be measured as the largest diameter seen on scan and the largest diameter perpendicular to that dimension. | up to 60 weeks | 
| Determine the Overall Survival of Patients | From the time of protocol initiation | up to 64 weeks | 
| Determine the Cause of Death of Patients After Treatment | To determine the cause of death (i.e., CNS tumor versus systemic disease progression) in patients after treatment. | up to 1 year | 
| The Incidence and Severity of Centeral Nervous System (CNS) Toxicities | To determine the incidence and severity of CNS toxicity in patients treated with intra-arterial carboplatin and oral temozolomide. | up to 24 weeks | 
| Quality of Life Assessment | To determine the impact of treatment on quality of life. | up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Symptomatic, Recurrent