SAFETY, FEASIBILITY AND COST-ANALYSIS OF UGT1A1 GENOTYPE-GUIDED DOSING OF IRINOTECA

Completed

Conditions: Adverse events
toxicity
10027656

Registration Number: NL-OMON49649

Lead Sponsor: Catharina-ziekenhuis

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 388

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

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).

Study & Design

Study Type: Observational invasive

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>The primary endpoint of the study is the incidence of febrile neutropenia of<br /><br>UGT1A1 genotype-guided dosing during the first two cycle of irinotecan<br /><br>treatment.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>* Incidence of grade 3 toxicity<br /><br> Incidence of toxicity-related hospital admissions<br /><br>* Number of patients with treatment delay, defined as a delay of more than 2<br /><br>days<br /><br>* Incidence of early treatment withdrawal<br /><br>* Pharmacokinetics of irinotecan and its metabolite SN-38 in UGT1A128 and/or<br /><br>93 homozygous variant allele carriers.<br /><br>* Incidence of treatment delay due to prospective screening of UGT1A1<br /><br>* Direct medical costs of irinotecan-based treatment<br /><br>* Progression free survival and overall survival<br /><br>* Bilirubin / conjugated bilirubin concentration ratio<br /><br>* The effect of additional polymorphisms other than UGT1A128 and 93 on<br /><br>treatment outcome in terms of toxicity and efficacy (survival and<br /><br>progression-free survival)</p><br>