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

Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00389584
• Other study ID #: CDR0000506074
• Secondary ID: UCDCC-132UCDCC-2
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 18, 2006
• Last updated: October 31, 2017
• Start date: December 2002
• Est. completion date: November 2006

Study information

• Verified date: October 2017
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2006
• Est. primary completion date: November 2006
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 120 Years

Eligibility

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)

Related Conditions & MeSH terms

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

Intervention

Drug:
• irinotecan hydrochloride

Procedure:
• cognitive assessment

• management of therapy complications

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	University of California Davis Cancer Center	Sacramento	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Davis

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose and toxicity as assessed by NCI CTC v2.0 (Phase I) (Phase I closed to accrual as of 4/15/05)
Primary	Overall survival (Phase II)
Secondary	Neurocognitive deterioration as assessed by Mini-Mental Status Examination (Phase II)
Secondary	Time to cognitive failure as assessed by Kaplan-Meier (Phase II)