Advanced EGFR mutation positive non small cell lung cancer, pancreatic carcinoma, colorectal cancer and biliary cancer MedDRA version: 21.1 Level: PT Classification code 10029522 Term: Non-small cell lung cancer stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Tarceva
Product Name: Erlotinib
Product Code: L01XE03
Pharmaceutical Form: Tablet
INN or Proposed INN: ERLOTINIB
CAS Number: 183321-74-6
Current Sponsor code: EMEA/H/C/000618
Other descri
Sponsors
Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients treated with single agent erlotinib 150mg QD, without disease progression at the first regular response evaluation after treatment initiation or patients who may benefit from erlotinib treatment • Age = 18 years • Accessible for repeated venipunctures • Ability to understand the study and give signed informed consent prior to beginning of protocol specific procedures 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 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: • Concomitant use of medication(s) which could influence the pharmacokinetics of erlotinib within 14 days or five half-lives of the drug (whichever is shorter) before start of the study, consisting of (but not limited to) CYP3A4-inhibitors/inductors • Active uncontrolled infection or severe cardiac dysfunction (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) • Impaired hepatic function (total bilirubin > ULN or Child-Pugh A, B and C) • Woman who are pregnant or breast feeding • Progression on erlotinib at the latest regular response evaluation • Current smokers or stopped smoking within 7 days before study allocation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of erlotinib, measured as AUC0-24h, AUCmean, Cmax and Cmin;Secondary Objective: 1. Safety of the CYP3A4 moderator ritonavir in combination with erlotinib, which will be measured as the incidence and severity of adverse events with and without ritonavir, according to CTC-AE v4.03. 2. The correlation between the pharmacokinetics, measured as AUC0-24h, AUCmean, Cmax and Cmin of ritonavir and toxicity according to CTC-AE v4.03 3. Study the effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of the active metabolite of erlotinib, OSI-420 , measured as AUC0-24h, AUCmean, Cmax and Cmin. 4. Quantification of ctDNA, determined with Droplet digital PCR (ddPCR) ;Primary end point(s): The effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of erlotinib, measured as AUC0-24h, Cmax and Cmin.;Timepoint(s) of evaluation of this end point: 15 days | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The incidence and severity of adverse events of co-administration of the highly potent CYP3A4 inhibitor ritonavir, according to CTC-AE v4.03. 2. To determine the correlation between the ritonavir pharmacokinetics (AUC0-24h, Cmax and Cmin) and the incidence and severity of adverse events. 3. To Study the effect of the highly potent CYP3A4 inhibitor ritonavir on the pharmacokinetics (PK) of the active metabolite of erlotinib OSI-420 , measured as AUC0-24h, Cmax and Cmin. 4. Quantification of ctDNA, determined with Droplet digital PCR (ddPCR) ;Timepoint(s) of evaluation of this end point: Not applicable | — |
Countries
Netherlands
Contacts
Public ContactDr. N. Steeghs
Stichting Het Nederlands Kanker Instituut-Antoni van Leuewenhoek Ziekenhuis
Outcome results
None listed