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

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.

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