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

• ClinicalTrials.gov Identifier: NCT00389584
• Recruitment Status: Completed
• First Posted: October 19, 2006
• Last Update Posted: November 6, 2017
• Sponsor: University of California, Davis
• Information provided by: University of California, Davis

Study Description

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:

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 Design

• 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

Arms and Interventions

Outcome Measures

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)

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 120 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• 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

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

• 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
• Other Study ID Numbers: CDR0000506074; UCDCC-132; UCDCC-200210643-5; PFIZER-Z1001692
• First Posted: October 19, 2006
• 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:

Neoplasms; Neoplasm Metastasis; Nervous System Neoplasms; Central Nervous System Neoplasms; Neoplastic Processes; Pathologic Processes; Neoplasms by Site; Nervous System Diseases; Irinotecan; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents