Irinotecan and Whole-Brain Radiation Therapy in Treating Patients With Brain Metastases From Solid Tumors
Condition: 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
MeSH terms: Neoplasms; Neoplasm Metastasis; Brain Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

Intervention name(s): irinotecan hydrochloride; cognitive assessment; management of therapy complications; radiation therapy
Intervention type(s): Drug; Procedure; Procedure; Radiation
Intervention MeSH terms: Irinotecan
Primary purpose: Treatment
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