Cancer
Conditions
Interventions
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: IRINOTECAN
CAS Number: 97682-44-5
Concentration unit: mg/ml milligram(s)/millilitre
Sponsors
Catharina Hospital Eindhoven
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathologically confirmed malignancy for which treatment with irinotecan is indicated at a dosing regimen of = 180 mg/m2 or 450-600mg flat dose in 2- or 3-weekly treatment schedules (see table 1) 2. Age = 18 years 3. Able and willing to give written informed consent 4. WHO performance status 0-2 5. Minimal acceptable safety laboratory values defined as a. ANC of = 1.5 x 109 /L b. Platelet count of = 100 x 109 /L c. Hepatic function as defined by serum bilirubin = 1.5 x ULN, ALAT and ASAT = 2.5 x ULN; in case of liver metastases ALAT and ASAT = 5 x ULN. d. Renal function (eGFR) = 50 ml/min OR creatinine = 1.5 x ULN Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 300 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 88
Exclusion criteria
Exclusion criteria: 1. Prior treatment with irinotecan 2. Patients with known substance abuse, psychotic disorders, and/or other diseases expected to interfere with study or the patient’s safety 3. Patients of Asian origin 4. Patients unable or unwilling to stop the use of (over the counter) medication or (herbal) supplements which can interact with irinotecan (e.g. by induction of inhibition of CYP3A4) (see Appendix 2 study protocol).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To develop a dosing nomogram of irinotecan in patients homozygous polymorphic for UGT1A1*28 and *93 in order to reduce the incidence of severe irinotecan-associated toxicity, defined as febrile neutropenia during the first two cycle of irinotecan treatment ; Secondary Objective: • To determine the effect of UGT1A1*28 and *93 genotype-guided dosing of irinotecan on the incidence of grade =3 toxicity, toxicity-related hospital admissions, treatment delay and early treatment withdrawal. • To confirm adequate drug exposure of UGT1A1*28 and *93 genotype-guided dosing by determining the pharmacokinetics of irinotecan in homozygous variant allele carriers. • To determine the feasibility of UGT1A1 genotype-guided dosing defined as no delay of treatment due to prospective screening of UGT1A1 genotype • To demonstrate that UGT1A1 genotype-guided dosing of irinotecan is cost-saving • To determine the effect of the dosing nomogram on efficacy of treatment • To determine the specificity and sensitivity of the bilirubin / conjugated bilirubin concentration ratio as a marker for the added value of genotyping for UGT1A1*28 and *93. • To retrospectively determine the effect of additional polymorphisms other than UGT1A1*28 and *93 on treatment outcome ;Primary end point(s): The primary endpoint of the study is the incidence of febrile neutropenia of UGT1A1 genotype-guided dosing during the first two cycles of irinotecan treatment;Timepoint(s) of evaluation of this end point: see study protocol, annex 14.1 study procedures | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Incidence of grade =3 toxicity • Incidence of toxicity-related hospital admissions • Number of patients with treatment delay, defined as a delay of more than 2 days • Incidence of early treatment withdrawal • Pharmacokinetics of irinotecan and its metabolite SN-38 in UGT1A1*28 and/or *93 homozygous variant allele carriers. • Incidence of treatment delay due to prospective screening of UGT1A1 • Direct medical costs of irinotecan-based treatment • Progression free survival and overall survival • Bilirubin / conjugated bilirubin concentration ratio • The effect of additional polymorphisms other than UGT1A1*28 and *93 on treatment outcome in terms of toxicity and efficacy (survival and progression-free survival) ;Timepoint(s) of evaluation of this end point: see study protocol, annex 14.1 study procedures | — |
Countries
Netherlands
Contacts
Public ContactClinical Pharmacy
Catharina Hospital Eindhoven
Outcome results
None listed