Cancer
Conditions
Interventions
Treatment with irinotecan 600mg 3-weekly with or without dietary restriction.
Sponsors
Erasmus MC, Universitair Medisch Centrum Rotterdam
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: *Metastatic colorectal cancer or other solid tumors *Eligible for treatment with irinotecan 600 mg 3-weekly *Age * 18 years *BMI 20-30kg/m2 *WHO performance status 0-1 *Written informed consent *Adequate renal function, i.e. serum creatinin 45 mL/min *Patients with safely accessible liver metastases and healthy liver tissue *Adequate coagulation status (PT-INR 6mmol/L, trombocyten > 100x10 9)
Exclusion criteria
Exclusion criteria: *Previous treatment with irinotecan within the last 6 months *Pregnant or lactating patients; patients with reproductive potential must use a reliable method of contraception (excluding oral contraceptives), if required. *Serious illness or medical unstable condition prohibiting adequate treatment and follow-up. *History of bleeding disorders (such as hemophilia) or bleeding complications from biopsies, dental procedures or surgeries. *Patients using any anti-coagulant medication which cannot be safely stopped or counteracted at the time of biopsy *Unable or unwilling to stop the use of (over the counter) medication of (herbal) supplements which can interact with irinotecan (e.g. by induction or inhibition of CYP3A4 (see Appendix B)) *Unable or unwilling to abstain from grapefruit or grapefruit juice during the study *Bilirubin > 1.5 x ULN, ASAT > 5x ULN, ALAT >5x ULN *Uncontrolled hypertension, despite medical treatment *Cows milk and/or soy allergy and/or lactose intolerance *Patients using insulin *Patients with hyperventilation *Patients unable of unwilling to fill in a food diary *Patients using oxygen and not able to stop for 30 minutes
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To demonstrate a 25% reduction of the active irinotecan metabolite, SN38, in healthy liver tissue (without reducing the intra-tumoral SN38 concentration), 24-26 hours after irinotecan administration with preceding dietary restriction compared to without preceding dietary restriction. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To determine intra-tumoral irinotecan and SN-38 concentrations with and without preceding dietary restriction. - To determine the systemic PK parameters of irinotecan in peripheral blood with and without preceding dietary restriction. - To determine leukocyte number with and without preceding dietary restriction - Toxicity of irinotecan with and without preceding dietary restriction. - Transcriptome analysis of tumor and liver to identify mechanisms responsible for increased intra-tumoral irinotecan concentrations and decreased side effects. | — |
Countries
Netherlands
Outcome results
None listed