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

Primary Purpose

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

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

carboplatin

tamoxifen citrate

topotecan hydrochloride

pharmacological study

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

City of Hope Comprehensive Cancer Center

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

NCT ID

NCT00541138

First Posted

October 5, 2007

Last Updated

September 20, 2011

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00541138

Brief Title

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

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 Type

Interventional

2. Study Status

Record Verification Date

September 2011

Overall Recruitment Status

Completed

Study Start Date

May 2003 (undefined)

Primary Completion Date

October 2007 (Actual)

Study Completion Date

October 2007 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

4. Oversight

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

carboplatin

Intervention Description

CBDCA AUC=3

Intervention Type

Drug

Intervention Name(s)

tamoxifen citrate

Intervention Description

Tamoxifen 100mg bid

Intervention Type

Drug

Intervention Name(s)

topotecan hydrochloride

Intervention Description

Topotecan 0.75 g/m2/d

Intervention Type

Other

Intervention Name(s)

pharmacological study

Intervention Description

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 Measure Information:

Title

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

Title

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

Title

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

Title

Reason for going off-study

Time Frame

Reported for all eligible patients

Title

Progression

Time Frame

Reported for all eligible patients

Title

Survival

Time Frame

Reported for all eligible patients

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Robert J. Morgan, MD

Organizational Affiliation

City of Hope Comprehensive Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

City of Hope Comprehensive Cancer Center

City

Duarte

State/Province

California

ZIP/Postal Code

91010-3000

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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