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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00541138
First received: October 5, 2007
Last updated: September 20, 2011
Last verified: September 2011

October 5, 2007
September 20, 2011
May 2003
October 2007   (final data collection date for primary outcome measure)
  • 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 ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Reason for going off-study [ Time Frame: Reported for all eligible patients ] [ Designated as safety issue: No ]
  • Progression [ Time Frame: Reported for all eligible patients ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: Reported for all eligible patients ] [ Designated as safety issue: No ]
  • Toxicity profile as assessed by NCI CTC v2.0
  • Response rate in patients with recurrent glial tumors as assessed by RECIST criteria
  • Response rate in patients with epithelial CNS metastases as assessed by RECIST criteria
  • Reason for going off-study
  • Progression
  • Survival
Complete list of historical versions of study NCT00541138 on ClinicalTrials.gov Archive Site
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Tamoxifen, Carboplatin, and Topotecan in Treating Patients With CNS Metastases or Recurrent Brain or Spinal Cord Tumors
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

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.

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Brain and Central Nervous System Tumors
  • Metastatic Cancer
  • Unspecified Adult Solid Tumor, Protocol Specific
  • 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.
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*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
50
October 2007
October 2007   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00541138
02191, P30CA033572, CHNMC-02191, CDR0000570253
Not Provided
City of Hope Medical Center
City of Hope Medical Center
National Cancer Institute (NCI)
Principal Investigator: Robert J. Morgan, MD Beckman Research Institute
City of Hope Medical Center
September 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP