High-Selenium Brassica Juncea, Irinotecan, and Capecitabine in Treating Patients With Advanced Cancer

NCT ID: NCT00547547

Last Updated: 2015-11-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2012-08-31

Brief Summary

RATIONALE: Brassica juncea that contains high amounts of selenium may slow the growth of cancer cells. Drugs used in chemotherapy, such as irinotecan and capecitabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving high-selenium Brassica juncea together with combination chemotherapy may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of high-selenium Brassica juncea and capecitabine when given together with irinotecan in treating patients with advanced cancer.

Detailed Description

OBJECTIVES:

Primary

• To determine the maximum tolerated dose of high-selenium Brassica juncea (BJ-Se) and capecitabine when administered in combination with irinotecan hydrochloride in patients with advanced malignancies.
• To determine the effects of BJ-Se on the pharmacokinetics of irinotecan hydrochloride and capecitabine.

Secondary

• To determine the effect of BJ-Se on the serum selenium and protein profile.
• To correlate response and tolerance to this regimen with expression of key enzymes involved as targets or with the metabolism of the components of treatment, including thymidylate synthase and dihydropyrimidine dehydrogenase.
• To evaluate changes to potential selenium related parameters.

OUTLINE: This is a multicenter, dose-escalation study of high-selenium Brassica juncea (BJ-Se) and capecitabine. The dose of capecitabine is escalated first, followed by dose escalation of BJ-Se.

Patients receive oral BJ-Se on days -7 to 21 in course 1 and on days 1-21 in all other courses. Patients also receive irinotecan IV on days 1 and 8 and oral capecitabine twice daily on days 1-14. Treatment repeats every 21 days in the absence of unacceptable toxicity or disease progression.

After the maximum tolerated dose (MTD) of capecitabine and BJ-Se are determined, additional patients are accrued and receive treatment at the MTD. Blood is collected from these patients during course 1 for pharmacokinetic studies.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (high-selenium therapy and chemotherapy)

Group Type: EXPERIMENTAL

high-selenium Brassica juncea

Intervention Type: DIETARY_SUPPLEMENT

Dose Level A: 3200 mcg orally day -7 through duration of treatment. Dose Level B: 4800 mcg orally day -7 through duration of treatment. Dose Level C: 6400 mcg orally day -7 through duration of treatment. Dose Level D: 7200 mcg orally day -7 through duration of treatment. Dose Level E: 8000 mcg orally day -7 through duration of treatment.

capecitabine

Intervention Type: DRUG

Dose Level 1: 750 mg/m2, 2x daily x 14 days every 21 days. Dose Level 1.5: 850 mg/m2, 2x daily x 14 days every 21 days. Dose Level 2: 1000 mg/m2, 2x daily x 14 days every 21 days.

irinotecan hydrochloride

Intervention Type: DRUG

Dose Level 1: 100 mg/m2 on day 1 and day 8 every 21 days. Dose Level -1: 75 mg/m2 on day 1 and day 8 every 21 days.

Interventions

high-selenium Brassica juncea

Dose Level A: 3200 mcg orally day -7 through duration of treatment. Dose Level B: 4800 mcg orally day -7 through duration of treatment. Dose Level C: 6400 mcg orally day -7 through duration of treatment. Dose Level D: 7200 mcg orally day -7 through duration of treatment. Dose Level E: 8000 mcg orally day -7 through duration of treatment.

Intervention Type: DIETARY_SUPPLEMENT

capecitabine

Dose Level 1: 750 mg/m2, 2x daily x 14 days every 21 days. Dose Level 1.5: 850 mg/m2, 2x daily x 14 days every 21 days. Dose Level 2: 1000 mg/m2, 2x daily x 14 days every 21 days.

Intervention Type: DRUG

irinotecan hydrochloride

Dose Level 1: 100 mg/m2 on day 1 and day 8 every 21 days. Dose Level -1: 75 mg/m2 on day 1 and day 8 every 21 days.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Patients with advanced, biopsy-proven cancer for which there is no standard curative therapy
• Karnofsky Performance status >= 60
• Prior therapy completed at least 3 weeks before protocol treatment initiation with recovery from any side-effects
• Prior capecitabine and/or irinotecan are allowed if subject did not progress while on treatment or within 6 months of treatment with these medications either alone or in combination
• Prior radiation therapy allowed if < 30% of marrow treated
• Alanine aminotransferase (ALT) and alkaline phosphatase with 3x upper limit of normal
• Serum bilirubin within normal limits
• Absolute neutrophil count >= 15000/ul
• Platelet count >= 100,000/ul
• Hemoglobin >= 10 gm/dl - transfusion allowed to achieve this
• Serum creatinine within 1.5 x upper limit of normal
• Ability to understand and sign an IRB approved informed consent
• Ability to use appropriate contraception and no evidence of pregnancy in female patients of reproductive potential

Exclusion Criteria

• No significant medical or psychiatric condition that would make treatment unsafe
• No active brain metastases (patients who have treated brain metastases and are stable off of steroids are eligible)
• Nursing women
• Patients must be able to comply with protocol related studies and follow-up
• Patients who are UGT1a1 7/7 positive will be excluded from the dose escalation portion of the trial, but may participate in the cohort of patients treated at the MTD

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Yun I. Yen, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

South Pasadena Cancer Center

Pasadena, California, United States

Countries

United States

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-05122

Identifier Type: -

Identifier Source: secondary_id

CDR0000570284

Identifier Type: REGISTRY

Identifier Source: secondary_id

05122

Identifier Type: -

Identifier Source: org_study_id