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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00541138

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Metastatic Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: carboplatin Drug: tamoxifen citrate Drug: topotecan hydrochloride Other: pharmacological study	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2003

Actual Primary Completion Date :

Oct 1, 2007

Actual Study Completion Date :

Oct 1, 2007

Outcome Measures

Primary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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