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

Primary Purpose

Brain and Central Nervous System Tumors, Cognitive/Functional Effects, Long-term Effects Secondary to Cancer Therapy in Adults

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

irinotecan hydrochloride

cognitive assessment

management of therapy complications

radiation therapy

About this trial

This is an interventional treatment trial for Brain and Central Nervous System Tumors focused on measuring 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

Eligibility Criteria

1 Year - 120 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

University of California Davis Cancer Center

Outcomes

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)

Overall survival (Phase II)

Secondary Outcome Measures

Neurocognitive deterioration as assessed by Mini-Mental Status Examination (Phase II)

Time to cognitive failure as assessed by Kaplan-Meier (Phase II)

Full Information

NCT ID

NCT00389584

First Posted

October 18, 2006

Last Updated

October 31, 2017

Sponsor

University of California, Davis

1. Study Identification

Unique Protocol Identification Number

NCT00389584

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

December 2002 (undefined)

Primary Completion Date

November 2006 (Actual)

Study Completion Date

November 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

University of California, Davis

4. Oversight

Data Monitoring Committee

Yes

5. 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)

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Drug

Intervention Name(s)

irinotecan hydrochloride

Intervention Type

Procedure

Intervention Name(s)

cognitive assessment

Intervention Type

Procedure

Intervention Name(s)

management of therapy complications

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Primary Outcome Measure Information:

Title

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

Title

Overall survival (Phase II)

Secondary Outcome Measure Information:

Title

Neurocognitive deterioration as assessed by Mini-Mental Status Examination (Phase II)

Title

Time to cognitive failure as assessed by Kaplan-Meier (Phase II)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Year

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Allan Y. Chen, MD, PhD

Organizational Affiliation

University of California, Davis

Official's Role

Study Chair

Facility Information:

Facility Name

University of California Davis Cancer Center

City

Sacramento

State/Province

California

ZIP/Postal Code

95817

Country

United States

12. IPD Sharing Statement

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

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