Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
- Conditions
- Drug MonitoringCarcinoma, Non-Small-Cell LungLung CancerAnaplastic Lymphoma Kinase Gene MutationAnaplastic Lymphoma Kinase Gene Translocation
- Interventions
- Registration Number
- NCT05525338
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
The ADAPT ALEC randomized controlled trial (RCT) is performed in patients with Anaplastic Lymphoma Kinase (ALK) positive non-small cell lung cancer (NSCLC). The RCT will compare the use of Therapeutic Drug Monitoring (TDM) and dose increases if alectinib 35 ng/Ml (arm A) with standard of care (arm B).
- Detailed Description
The ADAPT ALEC trial is a phase IV, RCT in patients with ALK positive NSCLC treated with alectinib. A longer median progression free survival (mPFS) is expected in patients treated with standard dose alectinib when minimum plasma concentrations (Cmin) of alectinib exceed 435 ng/mL. The ADAPT ALEC trial will investigate whether using therapeutic drug monitoring (TDM) and increasing the dose of alectinib in patients with Cmin \<435 ng/mL, will raise the mPFS. We will compare mPFS in the subgroup of patients with an alectinib Cmin \<435 ng/mL using TDM and dose increases (arm A) to fixed dosing/standard of care (arm B).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 196
- Patients with locally advanced or metastatic NSCLC (stage IIIB to stage IV by AJCC 8th)
- ECOG performance status 0-4
- Histologically or cytology confirmed NSCLC
- Documented ALK rearrangement based on an EMA approved test
- Patients can either be chemotherapy-naïve or have received one line of platinum-based chemotherapy
- Patients with brain or leptomeningeal metastases are allowed on the 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
- Measurable disease (by RECIST criteria version 1.1) prior to the first dose of study treatment
- Signed writte Institutional Review Board (IRB)/Ethical Committee (EC) approved informed consent form, prior to performing any study-related procedures
- Observational other studies are allwoed for patients included in this study
- Local radiotherapy is allowed for pain
- Any significant concomitant disease determined by the investigator to be potentially aggravated by the investigational drug
- 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)
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TDM-guided dosing arm Alectinib -
- Primary Outcome Measures
Name Time Method Median progression free survival (mPFS) mPFS will be assessed through study completion, after 12 months of follow-up. PFS is measured from start of treatment to progressive disease, death or lost to follow-up.Patients who did not die or progress, or lost to follow-up, will be censored at their last available date.
- Secondary Outcome Measures
Name Time Method Succesfull Therapeutic Drug monitoring 4 to 6 weeks after dose adjustment based on TDM The percentage of succesfull TDM interventions, in which successful is defines as tartget attainment and manageable toxicity.
Overall response rate (ORR) Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up ORR is the percentage of patients with partial response or complete response, according to RECIST v1.1, of the total treated population.
Incremental cost-effectiveness ratio (ICER) Through total study completion, after 12 months of follow-up The ICER is the final outcome of the comparative cost-effectiveness analysis performed using a health-state transition model to compare costs and effectiveness between both study arms.
Patient adherence to alectinib treatment Through study completion, an average of 2 years This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.
European Organization for Research and Treatment of Cancer 30-item core quality of life questionnaire (EORTC QLQ-C30) and the the Quality of Life Questionnaire-Lung Cancer 13 (EORTC QLQ-LC-13) module Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years. Mean change from baseline in EORTC QLQ-C30 and QLQ-LC13 scores
Median overall survival Through total study completion, after 12 months of follow-up mOS is defined as time from randomization to death from any cause in the total population.
Intracranial PFS Progressive disease will be assessed once every 2-3 months. Intracranial PFS will be assessed through total study completion, after 12 months of follow-up PFS is measured from start of treatment to progressive disease in the brain, death or lost to follow-up. Patients who did not die or progress, or lost to follow-up, will be censored at their last available date.
Number of adverse events (AE) related to plasma concentration and dose increases Through total study completion, after 12 months of follow-up AE's will be defined using CTCAE v5.0. Number of AE's in the subgroups of patients with Cmin \<435 ng/mL compared to Cmin \>= 435 ng/ML, and in patients who did and who did not receive a TDM-guided dose increase.
European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years. Mean change from baseline in EQ-5D-5L score
Alectinib M4 protein Through total study completion, after 12 months of follow-up Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations
Trial Locations
- Locations (8)
The Netherlands Cancer Institute
🇳🇱Amsterdam, Noord-Holland, Netherlands
Leiden University Medical Center
🇳🇱Leiden, Zuid-Holland, Netherlands
University Medical Center Groningen
🇳🇱Groningen, Netherlands
Radboud University Medical Center
🇳🇱Nijmegen, Gelderland, Netherlands
Gustave Roussy
🇫🇷Villejuif, Val-de-Marne, France
Erasmus Medical Center
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Maastricht University Medical Center +
🇳🇱Maastricht, Limburg, Netherlands
Amsterdam University Medical Center
🇳🇱Amsterdam, Noord-Holland, Netherlands