Irinotecan and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Solid Tumors

NCT ID: NCT00389584

Last Updated: 2017-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-12-31
• Study Completion Date: 2006-11-30

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as irinotecan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Irinotecan may make tumor cells more sensitive to radiation therapy. Giving irinotecan together with whole-brain radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of irinotecan when given together with whole-brain radiation therapy and to see how well they work in treating patients with brain metastases from solid tumors. (The study of side effects and best dose has ended as of 4/15/05)

Detailed Description

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of irinotecan hydrochloride administered concurrently with whole-brain radiotherapy in patients with brain metastases from solid tumors. (Phase I) (Phase I closed to accrual as of 4/15/05)
• Determine the toxicity of this regimen in these patients. (Phase I) (Phase I closed to accrual as of 4/15/05)
• Determine the overall survival of patients treated with this regimen. (Phase II)

Secondary

• Assess the neurocognitive function of these patients by Mini-Mental Status Examination. (Phase II)

OUTLINE: This is a phase I, dose-escalation study of irinotecan hydrochloride (phase I closed to accrual as of 4/15/05) followed by a phase II study. Patients enrolled in phase II are stratified according to cognitive dysfunction (yes vs no).

• Phase I (closed to accrual as of 4/15/05): Patients undergo whole-brain radiotherapy (WBRT) once daily, 5 days a week, for 3 weeks (15 fractions). Patients also receive irinotecan hydrochloride IV over 90 minutes on days 1, 8, and 15.

Cohorts of 3-6 patients receive escalating doses of irinotecan hydrochloride until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

• Phase II (for patients enrolled after 4/15/05): Patients receive irinotecan hydrochloride at the MTD and undergo concurrent WBRT as in phase I.

Patients complete the Mini-Mental Status Examination to assess neurocognitive function at baseline, on the last day of radiotherapy, and periodically after completion of study therapy.

After completion of study therapy, patients are followed monthly for 3 months, at 6 months, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 51 patients will be accrued for this study.

Conditions

Brain and Central Nervous System Tumors; Cognitive/Functional Effects; Long-term Effects Secondary to Cancer Therapy in Adults; Long-term Effects Secondary to Cancer Therapy in Children; Poor Performance Status; Unspecified Adult Solid Tumor, Protocol Specific; Unspecified Childhood Solid Tumor, Protocol Specific

Keywords

cognitive/functional effects; poor performance status; long-term effects secondary to cancer therapy in adults; long-term effects secondary to cancer therapy in children; adult tumors metastatic to brain; unspecified adult solid tumor, protocol specific; unspecified childhood solid tumor, protocol specific

Study Design

• Primary Study Purpose: TREATMENT

Interventions

irinotecan hydrochloride

Intervention Type: DRUG

cognitive assessment

Intervention Type: PROCEDURE

management of therapy complications

Intervention Type: PROCEDURE

radiation therapy

Intervention Type: RADIATION

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of brain metastasis from a histologically confirmed solid tumor, meeting the following criteria:

• Must have histologic proof of original malignancy
• No germ cell tumor metastasis
• Biopsy-proven brain metastasis preferred when clinical history and radiographic findings are equivocal
• At least 1 unidimensionally measurable lesion ≥ 50 mm by head contrast CT scan and/or brain MRI
• Patients enrolled in the phase II portion of the study must meet the following Radiation Therapy Oncology Group Recursive Partitioning Analysis staging criteria for brain metastases:

• Class II classification

• Zubrod performance status 0-1 AND any of the following:

• Age > 65 years
• Extracranial metastasis
• Uncontrolled primary malignancy

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1
• Life expectancy ≥ 3 months
• Able to participate in the Mini-Mental Status Examination
• WBC ≥ 3,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Bilirubin ≤ 1.5 mg/dL
• AST ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases are present)
• Hemoglobin ≥ 9.0 g/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No concurrent medical disease that, in the investigator's opinion, would preclude study participation

PRIOR CONCURRENT THERAPY:

• More than 21 days since prior chemotherapy
• No prior whole-brain radiotherapy
• No prior DNA topoisomerase I drugs (e.g., irinotecan hydrochloride, topotecan hydrochloride)
• At least 4 days since prior and no concurrent known CYP3A4 inducers, including any of the following:

• Phenytoin
• Carbamazepine
• Phenobarbital
• Hypericum perforatum (St. John's wort)

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of California, Davis

OTHER

Sponsor Role: lead

Responsible Party

Assistant Professor (no longer at UC Davis); not to be confused with Allen M. Chen, MD

Principal Investigators

Allan Y. Chen, MD, PhD

Role: STUDY_CHAIR

University of California, Davis

Locations

University of California Davis Cancer Center

Sacramento, California, United States

Countries

United States

Other Identifiers

UCDCC-132

Identifier Type: -

Identifier Source: secondary_id

UCDCC-200210643-5

Identifier Type: -

Identifier Source: secondary_id

PFIZER-Z1001692

Identifier Type: -

Identifier Source: secondary_id

CDR0000506074

Identifier Type: -

Identifier Source: org_study_id