Clinical trial NCT05525338: Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
Official title: Standard Dosed Alectinib Versus Therapeutic Drug Monitoring Guided Alectinib Dosing
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Drug Monitoring
Carcinoma, Non-Small-Cell Lung
Lung Cancer
Anaplastic Lymphoma Kinase Gene Mutation
Anaplastic Lymphoma Kinase Gene Translocation
Keywords: Alectinib
Randomized Controlled Trial
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Amsterdam University Medical Center
name: Erasmus Medical Center
name: Maastricht University Medical Center
name: Radboud University Medical Center
name: The Netherlands Cancer Institute
name: Leiden University Medical Center
First posted: 2022-09-01
Enrollment: 196
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Both study-arms will receive oral alectinib (Alecensa®, Roche). In arm A (TDM arm), the alectinib dose will be increased if Cmin \<435 ng/mL and manageable toxicity. In both arms, alectinib dose can be reduced based on toxicity.
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Median progression free survival (mPFS)
timeFrame: mPFS will be assessed through study completion, after 12 months of follow-up.
Secondary outcomes:
measure: Succesfull Therapeutic Drug monitoring
timeFrame: 4 to 6 weeks after dose adjustment based on TDM
measure: Overall response rate (ORR)
timeFrame: Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up
measure: Median overall survival
timeFrame: Through total study completion, after 12 months of follow-up
measure: Intracranial PFS
timeFrame: 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
measure: Patient adherence to alectinib treatment
timeFrame: Through study completion, an average of 2 years
measure: Number of adverse events (AE) related to plasma concentration and dose increases
timeFrame: Through total study completion, after 12 months of follow-up
measure: 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
timeFrame: Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
measure: European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire
timeFrame: Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
measure: Incremental cost-effectiveness ratio (ICER)
timeFrame: Through total study completion, after 12 months of follow-up
measure: Alectinib M4 protein
timeFrame: Through total study completion, after 12 months of follow-up
Other outcomes:
Locations:
city: Villejuif
country: France
facility: Gustave Roussy
state: Val-de-Marne
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center
state: Gelderland
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center +
state: Limburg
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute
state: Noord-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center
state: Noord-Holland
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: A.J. van der Wekken, PhD
role: PRINCIPAL_INVESTIGATOR
References: