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

Sponsors and Collaborators:	Beckman Research Institute National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00541138

Purpose

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	Intervention	Phase
Brain and Central Nervous System Tumors Unspecified Adult Solid Tumor, Protocol Specific	Drug: carboplatin Drug: tamoxifen citrate Drug: topotecan hydrochloride Other: pharmacological study	Phase II

Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Tamoxifen Carboplatin Tamoxifen citrate Topotecan hydrochloride Topotecan

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Toxicity profile as assessed by NCI CTC v2.0 [ Designated as safety issue: Yes ]
Response rate in patients with recurrent glial tumors as assessed by RECIST criteria [ Designated as safety issue: No ]
Response rate in patients with epithelial CNS metastases as assessed by RECIST criteria [ Designated as safety issue: No ]
Reason for going off-study [ Designated as safety issue: No ]
Progression [ Designated as safety issue: No ]
Survival [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	May 2003
Estimated Primary Completion Date:	October 2007 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00541138

Locations

United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000

Sponsors and Collaborators

Beckman Research Institute

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Robert J. Morgan, MD

Beckman Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	City of Hope Comprehensive Cancer Center ( Robert Joseph Morgan )
Study ID Numbers:	CDR0000570253, CHNMC-02191
Study First Received:	October 5, 2007
Last Updated:	April 3, 2009
ClinicalTrials.gov Identifier:	NCT00541138 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

adult 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

Study placed in the following topic categories:

Glioblastoma
Spinal Cord Diseases
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Central Nervous System Neoplasms
Selective Estrogen Receptor Modulators
Hormones
Ependymoma
Estrogen Receptor Modulators
Neoplasm Metastasis
Glioma
Nervous System Neoplasms
Estrogen Antagonists
Estrogens

Astrocytoma
Antineoplastic Agents, Hormonal
Spinal Cord Neoplasm
Citric Acid
Central Nervous System Diseases
Carboplatin
Tamoxifen
Recurrence
Brain Neoplasms
Citrate
Spinal Cord Neoplasms
Oligodendroglioma
Gliosarcoma
Topotecan

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Spinal Cord Diseases
Antineoplastic Agents
Hormone Antagonists
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Central Nervous System Neoplasms
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Neoplastic Processes
Neoplasms by Site
Pathologic Processes
Therapeutic Uses

Neoplasm Metastasis
Nervous System Neoplasms
Estrogen Antagonists
Antineoplastic Agents, Hormonal
Nervous System Diseases
Central Nervous System Diseases
Enzyme Inhibitors
Carboplatin
Tamoxifen
Pharmacologic Actions
Neoplasms
Spinal Cord Neoplasms
Topotecan

ClinicalTrials.gov processed this record on August 28, 2009