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

This study has been completed.
Sponsor:
Information provided by:
University of California, Davis
ClinicalTrials.gov Identifier:
NCT00389584
First received: October 18, 2006
Last updated: March 15, 2010
Last verified: March 2010
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I/II Study of Irinotecan and Whole Brain Radiation Therapy in Patients With Brain Metastases From Solid Tumors

Resource links provided by NLM:


Further study details as provided by University of California, Davis:

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) [ Designated as safety issue: Yes ]
  • Overall survival (Phase II) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Neurocognitive deterioration as assessed by Mini-Mental Status Examination (Phase II) [ Designated as safety issue: No ]
  • Time to cognitive failure as assessed by Kaplan-Meier (Phase II) [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: December 2002
Study Completion Date: November 2006
Primary Completion Date: November 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   1 Year and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00389584

Locations
United States, California
University of California Davis Cancer Center
Sacramento, California, United States, 95817
Sponsors and Collaborators
University of California, Davis
Investigators
Study Chair: Allan Y. Chen, MD, PhD University of California, Davis
  More Information

Additional Information:
No publications provided

Responsible Party: Allan Y. Chen, MD, PhD, Assistant Professor (no longer at UC Davis); not to be confused with Allen M. Chen, MD
ClinicalTrials.gov Identifier: NCT00389584     History of Changes
Other Study ID Numbers: CDR0000506074, UCDCC-132, UCDCC-200210643-5, PFIZER-Z1001692
Study First Received: October 18, 2006
Last Updated: March 15, 2010
Health Authority: United States: Federal Government

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:
Neoplasm Metastasis
Nervous System Neoplasms
Central Nervous System Neoplasms
Neoplasms
Neoplastic Processes
Pathologic Processes
Neoplasms by Site
Nervous System Diseases
Irinotecan
Camptothecin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs
Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014