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van CCT (UK)

van CCT (UK)

Dietary restriction followed by irinotecan chemotherapy

- candidate number24077
- NTR NumberNTR5731
- ISRCTNISRCTN no longer applicable
- Date ISRCTN created
- date ISRCTN requested
- Date Registered NTR4-mrt-2016
- Secondary IDsNL55597.078.15 
- Public TitleDietary restriction followed by irinotecan chemotherapy
- Scientific TitleEffects of a short-term dietary restriction regimen in cancer patients receiving irinotecan
- hypothesisShort 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
- Healt Condition(s) or Problem(s) studiedDietary restriction, Fasting, Colorectal metastised cancer, Irinotecan
- Inclusion criteria Metastatic colorectal cancer
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
- mec approval receivedyes
- multicenter trialno
- randomisedyes
- masking/blindingNone
- controlNot applicable
- groupCrossover
- Type2 or more arms, randomized
- Studytypeintervention
- planned startdate 11-mrt-2016
- planned closingdate11-mrt-2018
- Target number of participants18
- InterventionsStandard treatment with or without dietary restriction
- Primary outcomePrimary 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 as a result of preceding dietary restriction.
- Secondary outcomeSecondary objectives are systemic and intratumoral irinotecan pharmacokinetics and toxicity.
- TimepointsFirst and second cycle of irinotecan treatment.
- Trial web site
- status[default]
- Sponsor/Initiator Erasmus Medical Center, Rotterdam
- Funding
(Source(s) of Monetary or Material Support)
Erasmus Medical Center
- Publications
- Brief summaryCurrently, 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.
- Main changes (audit trail)3-jan-2017:Amendment

Inclusion NEW:
- Metastatic colorectal cancer and other solid tumors

Primary Outcome NEW:
in patients with mCRC and other solid tumors
- RECORD4-mrt-2016 - 3-jan-2017

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