Tamoxifen, Carboplatin, and Topotecan in Treating Patients With CNS Metastases or Recurrent Brain or Spinal Cord Tumors

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as carboplatin and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Tamoxifen may help carboplatin work better by making tumor cells more sensitive to the drug. PURPOSE: This phase II trial is studying the side effects of giving carboplatin and topotecan together with tamoxifen and to see how well it works in treating patients with central nervous system metastases or recurrent brain or spinal cord tumors.

Detailed Description
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OBJECTIVES: To evaluate the systemic and CNS response rates and progression-free and overall survival of patients with epithelial cancer and brain metastases treated with tamoxifen citrate, topotecan hydrochloride, and carboplatin. To evaluate the response rates, progression-free survival, and overall survival of patients with recurrent primary glial tumors treated with this regimen. To further assess the toxicity of these drugs in these patients. To further evaluate the pharmacokinetics of topotecan hydrochloride and tamoxifen citrate using paired specimens of cerebrospinal fluid and plasma from these patients. OUTLINE: Patients are stratified by disease type (epithelial CNS metastases vs recurrent glial tumors). Patients receive topotecan IV on days 1-3 (72 hours), carboplatin IV over 30 minutes on day 4, and oral tamoxifen twice daily on days 1-7. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Patients achieving a complete response (CR) may be treated for 2 additional courses after documentation of CR. Patients undergo blood sample collection at baseline and then periodically after the first dose of topotecan to obtain plasma pharmacokinetic (PK) measurements of topotecan and tamoxifen. Some patients may also undergo cerebrospinal fluid (CSF) collection to assess peak CSF levels of topotecan and tamoxifen during course 1.

Official Title
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A Pilot Study of Tamoxifen, Carboplatin and Topotecan in the Treatment of Recurrent or Refractory Primary Brain or Spinal Cord Tumors or Metastatic Epithelial Cancers With Central Nervous System Metastases

Conditions
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Brain and Central Nervous System Tumors, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: carboplatin
* Drug: tamoxifen citrate
* Drug: topotecan hydrochloride
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of 1 of the following: Epithelial neoplasms metastatic to the central nervous system Recurrent or refractory to prior chemotherapeutic or radiotherapeutic regimens or for which no standard chemotherapy or whole brain radiotherapy regimens exist Stage IV disease Recurrent glial tumors (brain or spinal cord) Received prior whole brain radiotherapy or stereotactic radiotherapy OR refused radiotherapy Patients with CNS metastases previously treated with radiotherapy are eligible, provided persistent or progressive CNS metastases are documented by MRI eight weeks after the end of radiotherapy Patients with glial tumors must show progressive disease by MRI after prior radiotherapy Measurable disease in the brain/leptomeninges of the brain or spinal cord with baseline documentation within 4 weeks of study entry Must have ≥ 1 lesion that is ≥ 1 cm on MRI scan Ineligible for or has refused participation in higher priority institutional protocols PATIENT CHARACTERISTICS: Karnofsky performance status 50-100% Life expectancy ≥ 2 months Creatinine ≤ 1.5 mg/dL WBC 4,000/mm³ OR ANC ≥ 2,000/mm³ Platelet count ≥ 150,000/mm³ Bilirubin ≤ 1.5 mg/dL ALT and AST < 2 times upper limit of normal Not pregnant Negative pregnancy test Fertile patients must use effective contraception No nonmalignant concurrent illness (e.g., cardiovascular or pulmonary) that is either poorly controlled with currently available treatment or of such severity to preclude study entry No severe infection Patients who are ineligible for lumbar puncture are allowed PRIOR CONCURRENT THERAPY: See Disease Characteristics At least 3 weeks since prior radiotherapy, immunotherapy, or chemotherapy OR recovered from expected side effects of prior therapy No patients who are recovering from major surgery No concurrent radiotherapy Concurrent steroid or anticonvulsant therapy allowed

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

| Intervention/Treatment |
| --- |
|Drug: carboplatin|CBDCA AUC=3|
|Drug: tamoxifen citrate|Tamoxifen 100mg bid|
|Drug: topotecan hydrochloride|Topotecan 0.75 g/m2/d|
|Other: pharmacological study|Start of tx, hours 24,28 and 72 during Topotecan infusion, and hours 1,2,4 and 6 after end of Topotecan infusion.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity profile as assessed by NCI CTC v2.0 |  | All patients who complete one course of therapy and are followed a minimum of 3 weeks after completion of first course of therapy | 
| Response rate in patients with recurrent glial tumors as assessed by RECIST criteria |  | All patients who complete at least one cycle of treatment | 
| Response rate in patients with epithelial CNS metastases as assessed by RECIST criteria |  | All patients who complete at least one cycle of treatment | 
| Reason for going off-study |  | Reported for all eligible patients | 
| Progression |  | Reported for all eligible patients | 
| Survival |  | Reported for all eligible patients | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tumors metastatic to brain, recurrent adult brain tumor, adult anaplastic astrocytoma, adult diffuse astrocytoma, adult giant cell glioblastoma, adult gliosarcoma, adult pilocytic astrocytoma, adult pineal gland astrocytoma, adult subependymal giant cell astrocytoma, adult brain stem glioma, adult anaplastic ependymoma, adult ependymoma, adult myxopapillary ependymoma, adult subependymoma, adult anaplastic oligodendroglioma, adult oligodendroglioma, unspecified adult solid tumor, protocol specific, adult mixed glioma