ALK fusion in stage IV NSCLC
Conditions
Interventions
ECG, bloodsampling, scans, optional biopsy
Sponsors
University Medical Center Groningen
Eligibility
Inclusion criteria
Inclusion criteria: 1. Patients with locally advanced or metastatic NSCLC (stage IIIB to stage IV by AJCC 8th) 2. Male or female =18 years old 3. ECOG Performance Status of 0-2 4. Histologically or cytology confirmed NSCLC 5. Documented ALK rearrangement based on an EMA approved test 6. Patients can either be chemotherapy-naïve or have received one line of platinum-based chemotherapy 7. Patients with brain or leptomeningeal metastases are allowed on study if the lesions are asymptomatic without neurological signs and clinically stable for at least 2 weeks without steroid treatment. Patients who do not meet these criteria are not eligible for the study. However, they can be re-screened after completing WBRT or gamma –knife treatment. They must have completed any corticosteroid therapy =2 weeks prior to the first dose of study treatment. 8. Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment 9. Signed written Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures.
Exclusion criteria
Exclusion criteria: 1. Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug 2. Consumption of agents which modulate CYP3A4 or agents with potential QT prolonging effects within 14 days prior to admission and during the study (see concomitant medication restrictions) 3. Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or absorption of oral medications, or that would, in the opinion of the Principal Investigator, pose an unacceptable risk to the subject in this study. 4. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol requirements and/or follow-up procedures; those conditions should be discussed with the patient before trial entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoint is a a prolonged mPFS in the TDM-guided dosing arm for the subgroup who had a Cmin < 435 ng/mL at a certain time point during treatment, compared to these patients in the fixed dosing arm | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Feasibility and tolerability of TDM. This will be measured as percentage of successful TDM measures, in which successful is defined as target attainment with manageable toxicity. 2. Overall response rates (ORR). ORR will be defined as partial response or complete response (according to RECIST v1.1) percentage of the total treated population. 3. Median overall survival (mOS). OS will be defined as the time from randomization to death from any cause in the total population 4. Patient adherence. This will be measured by the amount of drugs that are taken by the patients diary. 5. Physician adherence. This will be measured as the percentage of dose recommendations that is implemented by the treating physicians. 6. Toxicity related to the plasma concentration and dose increases. This will be defined as AE’s in the subgroups with Cmin < 435 ng/mL and all Cmin = 435 ng/mL, and in patients who did and who did not receive a PK-guided dose increase. | — |
Contacts
Public ContactA.J. van der Wekken
University Medical Centre Groningen
Outcome results
None listed