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

October 31, 2017 updated by: University of California, Davis

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

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)

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Sacramento, California, United States, 95817
        • University of California Davis Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Davis

Investigators

  • Study Chair: Allan Y. Chen, MD, PhD, University of California, Davis

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2002

Primary Completion (Actual)

November 1, 2006

Study Completion (Actual)

November 1, 2006

Study Registration Dates

First Submitted

October 18, 2006

First Submitted That Met QC Criteria

October 18, 2006

First Posted (Estimate)

October 19, 2006

Study Record Updates

Last Update Posted (Actual)

November 6, 2017

Last Update Submitted That Met QC Criteria

October 31, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000506074
  • UCDCC-132
  • UCDCC-200210643-5
  • PFIZER-Z1001692

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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