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

Phase 4RecruitingNCT05525338

University Medical Center Groningen196 enrolled

Overview

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).

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

196

Conditions

Drug Monitoring Carcinoma, Non-Small-Cell Lung Lung Cancer

Interventions

AlectinibDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (8)

Gustave Roussy

Villejuif, Val-de-Marne, France

NOT_YET_RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

RECRUITING

Maastricht University Medical Center +

Maastricht, Limburg, Netherlands

RECRUITING

The Netherlands Cancer Institute

Amsterdam, North Holland, Netherlands

RECRUITING

Amsterdam University Medical Center

Amsterdam, North Holland, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, South Holland, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, Netherlands

RECRUITING

Outcomes

Primary Outcomes

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.

Time frame: mPFS will be assessed through study completion, after 12 months of follow-up.

Secondary Outcomes

Succesfull Therapeutic Drug monitoring

The percentage of succesfull TDM interventions, in which successful is defines as tartget attainment and manageable toxicity.

Time frame: 4 to 6 weeks after dose adjustment based on TDM

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.

Time frame: Response will be assessed every 2-3 months. ORR will be determined after total study completion and 12 months of follow-up

Median overall survival

mOS is defined as time from randomization to death from any cause in the total population.

Time frame: Through total study completion, after 12 months of follow-up

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.

Time frame: 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

Patient adherence to alectinib treatment

This will be estimated by pill counts of returned medication as well as a patient diary on drug intake.

Time frame: Through study completion, an average of 2 years

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.

Time frame: Through total study completion, after 12 months of follow-up

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

Time frame: Questionnaires will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.

European Quality of Life Five Dimensions with five levels (EQ-5D-5L) questionnaire

Mean change from baseline in EQ-5D-5L score

Time frame: Questionnaire will be filled in at baseline and every 3 months thereafter through study completion, an average of 2 years.

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.

Time frame: Through total study completion, after 12 months of follow-up

Alectinib M4 protein

Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations

Time frame: Through total study completion, after 12 months of follow-up

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

Overview

Conditions

Interventions

Eligibility

Locations (8)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts