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ID
Source
Brief title
Health condition
Dietary restriction
Fasting
Metastatic colorectal carcinoma
Irinotecan
Dieetrestrictie
Vasten
Gemetastaseerd colorectaal carcinoom
Irinotecan
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary objective is to demonstrate a 25% reduction of the active irinotecan metabolite, SN38, in healthy liver tissue (without reducing the intra-tumoral SN38 concentration) in patients with mCRC and other solid tumors as a result of preceding dietary restriction.
Secondary outcome
Secondary objectives are systemic and intratumoral irinotecan pharmacokinetics and toxicity.
Background summary
Currently, more than half of the metastatic colorectal cancer patients do not benefit (optimally) from intravenously administered irinotecan as second line treatment. In recent preclinical studies in mice we have shown that the anti-tumor effects of irinotecan can be enhanced by fasting before irinotecan treatment. In addition, toxicity may be seriously reduced by fasting. While mice are significantly protected from the side effects of irinotecan chemotherapy after 72 hours of fasting, SN-38 (the active irinotecan metabolite) concentrations in both plasma and liver were significantly lower and intra-tumoral drug concentrations tend to be higher. The DIRINO study is a randomised two-arm cross-over study during which patients with mCRC and other solid tumors will be using a dietary restriction regimen for five days prior to the first or second irinotecan cycle. Primary endpoint is to demonstrate a 25% reduction of the SN-38 concentrations in healthy liver tissue (without reducing the intra-tumoral SN-38 concentration) 24 hours after irinotecan administration with preceding dietary restriction compared to no preceding dietary restriction. Secondary objectives are toxicity, systemic and intra-tumoral irinotecan pharmacokinetics.
Study objective
Short term dietary restriction will lead to lower concentrations of SN-38 in healthy liver tissue (without reducing the intratumoral concentration) and to less toxicity of irinotecan
Study design
First and second cycle of irinotecan treatment.
Intervention
Standard treatment with or without dietary restriction
F.M. de Man
‘s Gravendijkwal 230
Rotterdam 3015 CE
The Netherlands
Tel: +31 (0)10 7042451
f.deman@erasmusmc.nl
F.M. de Man
‘s Gravendijkwal 230
Rotterdam 3015 CE
The Netherlands
Tel: +31 (0)10 7042451
f.deman@erasmusmc.nl
Inclusion criteria
• Metastatic colorectal cancer and other solid tumors
• Treatment with irinotecan 600 mg 3-weekly
• Age ≥ 18 years
• BMI:20-30 kg/m2
• WHO performance status 0-1
• Written informed consent
• Adequate renal function, i.e. serum creatinin < 2 x ULN and creatinin clearance > 45 mL/min (calculated with Cockroft-Gault formula)
• Patients with safely accessible liver metastases and healthy liver tissue
• Adequate coagulation status as measured by:
o PT-INR < 1.5
o APTT < 1.5 x ULN
o Hb > 6 mmol/L
Note: Red blood cell transfusions are allowed to increase the Hb at the discretion of the investigator, but not during blood withdrawal for PK-analysis. Any necessary red blood cell transfusions during the first three cycles of irinotecan will be reported in the article.
o Platelet count > 100 x 109/L
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: all aspirin derivatives, NSAIDs, coumarines, platelet function inhibitors, heparins (including LMWHs) and oral factor Xa inhibitors.
• 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))
• 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
• Unable or unwilling to abstain from grapefruit or grapefruit juice during the study
• Bilirubin > 1.5 x ULN, AF > 5x ULN, ASAT > 5x ULN, ALAT >5x ULN
• Uncontrolled hypertension, despite medical treatment
• Cows milk and/or soy allergy and/or lactose intolerance
Design
Recruitment
IPD sharing statement
Plan description
Followed up by the following (possibly more current) registration
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| NTR-new | NL5624 |
| NTR-old | NTR5731 |
| CCMO | NL55597.078.15 |
| OMON | NL-OMON43513 |