Patients diagnosed with a neoplasm and treated with a tyrosine kinase inhibitor which is mainly metabolised by CYP3A4.
Conditions
Interventions
Trade Name: Cabozantinib/Cabometyx
Pharmaceutical Form: Film-coated tablet
Trade Name: Cobimetinib/Cotellic
Pharmaceutical Form: Film-coated tablet
Trade Name: Dabrafenib/Tafinlar
Pharmaceutical For
Sponsors
Erasmus MC Cancer Institute
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Indication to start treatment with TKI which is preliminary mainly metabolised by CYP3A4; 2. Proven malignancy; 3. Age =>18 years; 4. Able and willing to give written informed consent; 5. WHO performance status of 0, 1 or 2; 6. Able and willing to undergo blood sampling for PK and genetic analysis; 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 119 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 79
Exclusion criteria
Exclusion criteria: 1. Pregnant or lactating women; 2. Patients with known alcoholism, drug addiction and/or psychiatric of physiological condition which in the opinion of the investigator would impair treatment compliance; 3. Serious illness or medical unstable condition prohibiting adequate treatment and follow-up; 4. Therapy with TKI has been started more than 7 days before date of inclusion/informed consent; 5. Unable or unwilling to stop the use of (over the counter) medication or (herbal) supplements which are known or suspected to strongly inhibit or induct the CYP3A4 enzymes;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To compare toxicity grades (based on CTCAE) between carriers and non-carriers. - After pharmacokinetic assessment the dose may be adjusted based on clinical presentation and toxicity; incidence of dose modifications after four weeks will be compared using descriptive statistics between carriers and non-carriers.;Primary end point(s): To compare the Ctrough 2-4 weeks (depending on drug) after reporting of the CYP3A4 mutation status (or the latest moment possible in case of toxicity or treatment discontinuation) between the CYP3A4*22 carrier group and wild type patients.;Timepoint(s) of evaluation of this end point: End of study;Main Objective: To demonstrate that a dose reduction of 20-33% of CYP3A4 metabolized tyrosine kinase inhibitors in patients expressing the CYP3A4*22 gene (rs35599367 C>T in intron 6) does not result in a lower exposure (Ctrough) than the wildtype group with the usual dose. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - To compare toxicity grades (based on CTCAE) between carriers and non-carriers. - After pharmacokinetic assessment the dose may be adjusted based on clinical presentation and toxicity; incidence of dose modifications after four weeks will be compared using descriptive statistics between carriers and non-carriers.;Timepoint(s) of evaluation of this end point: End of study | — |
Countries
Netherlands
Contacts
Public ContactStijn Koolen
Erasmus MC
Outcome results
None listed