Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels

Lung Cancer Clinical Trial

— ADAPT ALEC  

Official title:

Standard Dosed Alectinib Versus Therapeutic Drug Monitoring Guided Alectinib Dosing

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05525338
• Other study ID #: 202000251
• Secondary ID: 2020-001737-13NL
• Status: Recruiting
• Phase: Phase 4
• Start date: March 23, 2022
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2024
• Source: University Medical Center Groningen
• Contact: M.B. Muntinghe-Wagenaar, Msc
• Phone: +31503616161
• Email: adaptalec[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 196
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Anaplastic Lymphoma Kinase Gene Mutation
• Anaplastic Lymphoma Kinase Gene Translocation
• Carcinoma, Non-Small-Cell Lung
• Drug Monitoring
• Lung Cancer
• Lymphoma

Intervention

Drug:
• Alectinib
In case of an alectinib plasmaconcentration Cmin <435 ng/mL, determined by TDM, and manageable toxicity, the alectinib dose will be increased with 150mg BID up to a maximum of 900mg BID. In case of unacceptable toxicity (i.e. unbearable or persistent grade 2 toxicity and grade 3/4 toxicity), the alectinib dose can be reduced by 150mg BID.

Locations

Country	Name	City	State
France	Gustave Roussy	Villejuif	Val-de-Marne
Netherlands	Amsterdam University Medical Center	Amsterdam	Noord-Holland
Netherlands	The Netherlands Cancer Institute	Amsterdam	Noord-Holland
Netherlands	University Medical Center Groningen	Groningen
Netherlands	Leiden University Medical Center	Leiden	Zuid-Holland
Netherlands	Maastricht University Medical Center +	Maastricht	Limburg
Netherlands	Radboud University Medical Center	Nijmegen	Gelderland
Netherlands	Erasmus Medical Center	Rotterdam	Zuid-Holland

Sponsors (7)

Lead Sponsor	Collaborator
University Medical Center Groningen	Amsterdam University Medical Center, Erasmus Medical Center, Leiden University Medical Center, Maastricht University Medical Center, Radboud University Medical Center, The Netherlands Cancer Institute

Countries where clinical trial is conducted

France,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Median progression free survival (mPFS)	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.	mPFS will be assessed through study completion, after 12 months of follow-up.
Secondary	Succesfull Therapeutic Drug monitoring	The percentage of succesfull TDM interventions, in which successful is defines as tartget attainment and manageable toxicity.	4 to 6 weeks after dose adjustment based on TDM
Secondary	Overall response rate (ORR)	ORR is the percentage of patients with partial response or complete response, according to RECIST v1.1, of the total treated population.	Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up
Secondary	Median overall survival	mOS is defined as time from randomization to death from any cause in the total population.	Through total study completion, after 12 months of follow-up
Secondary	Intracranial PFS	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.	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
Secondary	Patient adherence to alectinib treatment	This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.	Through study completion, an average of 2 years
Secondary	Number of adverse events (AE) related to plasma concentration and dose increases	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.	Through total study completion, after 12 months of follow-up
Secondary	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	Mean change from baseline in EORTC QLQ-C30 and QLQ-LC13 scores	Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
Secondary	European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire	Mean change from baseline in EQ-5D-5L score	Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.
Secondary	Incremental cost-effectiveness ratio (ICER)	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.	Through total study completion, after 12 months of follow-up
Secondary	Alectinib M4 protein	Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations	Through total study completion, after 12 months of follow-up