Brain and Central Nervous System Tumors, Metastatic Cancer, Unspecified Adult Solid Tumor, Protocol Specific
Conditions
Keywords
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
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.
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.
Interventions
DRUGcarboplatin
CBDCA AUC=3
DRUGtamoxifen citrate
Tamoxifen 100mg bid
DRUGtopotecan hydrochloride
Topotecan 0.75 g/m2/d
OTHERpharmacological study
Start of tx, hours 24,28 and 72 during Topotecan infusion, and hours 1,2,4 and 6 after end of Topotecan infusion.
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Response rate in patients with recurrent glial tumors as assessed by RECIST criteria | All patients who complete at least one cycle of treatment |
| 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 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 |
Countries
United States
Outcome results
None listed