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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00389584
Recruitment Status : Completed
First Posted : October 19, 2006
Last Update Posted : November 6, 2017
Information provided by:
University of California, Davis

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:



  • 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)


  • 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.

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Study Type : Interventional  (Clinical Trial)
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 : December 2002
Actual Primary Completion Date : November 2006
Actual Study Completion Date : November 2006

Resource links provided by the National Library of Medicine

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

Secondary Outcome Measures :
  1. Neurocognitive deterioration as assessed by Mini-Mental Status Examination (Phase II)
  2. Time to cognitive failure as assessed by Kaplan-Meier (Phase II)

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   1 Year to 120 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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


  • 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


  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00389584

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United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
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Study Chair: Allan Y. Chen, MD, PhD University of California, Davis
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Responsible Party: Allan Y. Chen, MD, PhD, Assistant Professor (no longer at UC Davis); not to be confused with Allen M. Chen, MD Identifier: NCT00389584    
Other Study ID Numbers: CDR0000506074
First Posted: October 19, 2006    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: October 2017
Keywords provided by University of California, Davis:
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
Additional relevant MeSH terms:
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Neoplasm Metastasis
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Nervous System Diseases
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents