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

Sponsored by:	University of California, Davis
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00389584

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 Cancer-Related Problem/Condition Unspecified Adult Solid Tumor, Protocol Specific Unspecified Childhood Solid Tumor, Protocol Specific	Drug: irinotecan hydrochloride Procedure: cognitive assessment Procedure: management of therapy complications Procedure: radiation therapy	Phase I Phase II

MedlinePlus related topics: Cancer

Drug Information available for: Irinotecan Irinotecan hydrochloride

U.S. FDA Resources

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

Further study details as provided by National Cancer Institute (NCI):

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 ]

Estimated Enrollment:	51
Study Start Date:	December 2002

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

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 Chen, MD

University of California, Davis

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000506074, UCDCC-132, UCDCC-200210643-5, PFIZER-Z1001692
Study First Received:	October 18, 2006
Last Updated:	October 18, 2008
ClinicalTrials.gov Identifier:	NCT00389584
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Irinotecan
Neoplasm Metastasis
Central Nervous System Neoplasms
Camptothecin
Nervous System Neoplasms

Additional relevant MeSH terms:

Neoplastic Processes
Neoplasms
Neoplasms by Site
Pathologic Processes
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Nervous System Diseases
Enzyme Inhibitors
Antineoplastic Agents, Phytogenic
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009