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

Phase 1

Completed

Conditions: Brain Tumor
Brain Metastases

Interventions: Drug: carboplatin
Drug: temozolomide

Registration Number: NCT00362817

Lead Sponsor: Ohio State University Comprehensive Cancer Center

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Pathologically confirmed systemic cancer

Exclusion Criteria

Pregnant
Known CNS meningeal involvement with cancer

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Temozolomide & Intra-Arterial (IA) carboplatin	carboplatin	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin
Temozolomide & Intra-Arterial (IA) carboplatin	temozolomide	Patients will be administered Temozolomide orally once a day for 5 consecutive days and and will receive Intra Arterial Carboplatin

Primary Outcome Measures

Name	Time	Method
Affects of Response Rate of Chemotherapy With Intra-arterial Carboplatin and Oral Temozolomide	up to 1 year	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.

Secondary Outcome Measures

Name	Time	Method
Analyze Patients Time to Progression	up to 60 weeks	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.
Quality of Life Assessment	up to 2 years	To determine the impact of treatment on quality of life.
Determine the Cause of Death of Patients After Treatment	up to 1 year	To determine the cause of death (i.e., CNS tumor versus systemic disease progression) in patients after treatment.
The Incidence and Severity of Centeral Nervous System (CNS) Toxicities	up to 24 weeks	To determine the incidence and severity of CNS toxicity in patients treated with intra-arterial carboplatin and oral temozolomide.
Determine the Overall Survival of Patients	up to 64 weeks	From the time of protocol initiation