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

Sponsor

University of California, Davis (Other)

Overall Status

Completed

CT.gov ID

NCT00389584

Collaborator

(none)

Enrollment

Location

Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
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	Drug: irinotecan hydrochloride Procedure: cognitive assessment Procedure: management of therapy complications Radiation: radiation therapy	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

30 participants

Primary Purpose:

Treatment

Official Title:

Phase I/II Study of Irinotecan and Whole Brain Radiation Therapy in Patients With Brain Metastases From Solid Tumors

Study Start Date :

Dec 1, 2002

Actual Primary Completion Date :

Nov 1, 2006

Actual Study Completion Date :

Nov 1, 2006

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose and toxicity as assessed by NCI CTC v2.0 (Phase I) (Phase I closed to accrual as of 4/15/05) []
Overall survival (Phase II) []

Secondary Outcome Measures

Neurocognitive deterioration as assessed by Mini-Mental Status Examination (Phase II) []
Time to cognitive failure as assessed by Kaplan-Meier (Phase II) []

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)