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


Phase 1/Phase 2
1 Year
N/A
Not Enrolling
Both
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

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Trial Information

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


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.

Inclusion 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)

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

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

Safety Issue:

Yes

Principal Investigator

Allan Y. Chen, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, Davis

Authority:

United States: Federal Government

Study ID:

CDR0000506074

NCT ID:

NCT00389584

Start Date:

December 2002

Completion Date:

November 2006

Related Keywords:

  • 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
  • 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
  • Neoplasm Metastasis
  • Nervous System Neoplasms
  • Central Nervous System Neoplasms
  • Neoplasms

Name

Location

University of California Davis Cancer CenterSacramento, California  95817