Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00541138
Recruitment Status : Completed
First Posted : October 8, 2007
Last Update Posted : September 21, 2011
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center

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:


  • 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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 2003
Actual Primary Completion Date : October 2007
Actual Study Completion Date : October 2007

Intervention Details:
  • Drug: carboplatin
  • 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.

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00541138

Layout table for location information
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000
Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Layout table for investigator information
Principal Investigator: Robert J. Morgan, MD City of Hope Comprehensive Cancer Center
Layout table for additonal information
Responsible Party: City of Hope Medical Center Identifier: NCT00541138    
Other Study ID Numbers: 02191
P30CA033572 ( U.S. NIH Grant/Contract )
CDR0000570253 ( Registry Identifier: NCI PDQ )
First Posted: October 8, 2007    Key Record Dates
Last Update Posted: September 21, 2011
Last Verified: September 2011
Keywords provided by City of Hope Medical Center:
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Nervous System Neoplasms
Central Nervous System Neoplasms
Spinal Cord Neoplasms
Neoplasms by Site
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents