Clinical trial NCT00547547: High-Selenium Brassica Juncea, Irinotecan, and Capecitabine in Treating Patients With Advanced Cancer
Official title: A Phase I Study of a Combination of High Selenium Brassica Juncea With Irinotecan and Capecitabine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-10-22
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Maximum tolerated dose of high-selenium Brassica juncea, irinotecan hydrochloride and capecitabine
timeFrame: After two 21 day cycles of treatment
measure: Toxicity
timeFrame: After two 21 day cycles of treatment
measure: Pharmacokinetics
timeFrame: For patients treated at the MTD only at the end of cycle one of treatment
Secondary outcomes:
measure: Serum selenium and protein profile
timeFrame: 21 days after the start of the last cycle of treatment
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Medical Center
state: California
city: Pasadena
country: United States
facility: South Pasadena Cancer Center
state: California
Study officials:
affiliation: City of Hope Medical Center
name: Yun I. Yen, MD
role: PRINCIPAL_INVESTIGATOR
References: