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

NCT05525338 | Recruiting Phase 4 DMC

• 3 other identifiers: 2020002512020-001737-13NL9411
• Study Type: interventional
• Target: 196
• Locations: 2 countries
• Sites: 8

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).

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Succesfull Therapeutic Drug monitoring

  4 to 6 weeks after dose adjustment based on TDM

• 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

• Median overall survival

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

• 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

• Patient adherence to alectinib treatment

  Through study completion, an average of 2 years

Study Arms (2)

TDM-guided dosing arm

EXPERIMENTAL

Drug: Alectinib

Standard dose arm

NO INTERVENTION

Alectinib plasmaconcentration will be blinded untill the end of the trial. No intervention based on the alectinib plasmaconcentrion will be performed. 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.

Interventions

Alectinib DRUG

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.

TDM-guided dosing arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Groningen: lead
• Amsterdam University Medical Center: collaborator
• Erasmus Medical Center: collaborator
• Maastricht University Medical Center: collaborator
• Radboud University Medical Center: collaborator
• The Netherlands Cancer Institute: collaborator
• Leiden University Medical Center: collaborator

Study Sites (8)

Gustave Roussy

Villejuif, Val-de-Marne, 94805, France

NOT YET RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, 6525 GA, Netherlands

RECRUITING

Maastricht University Medical Center +

Maastricht, Limburg, 6229 HX, Netherlands

RECRUITING

The Netherlands Cancer Institute

Amsterdam, North Holland, 1066 CX, Netherlands

RECRUITING

Amsterdam University Medical Center

Amsterdam, North Holland, 1105 AZ, Netherlands

RECRUITING

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, 3015 GD, Netherlands

RECRUITING

University Medical Center Groningen

Groningen, 9713GZ, Netherlands

RECRUITING

Related Publications (1)

• Meertens M, Muntinghe-Wagenaar MB, Sikkema BJ, Lopez-Yurda M, Retel VP, Paats MS, Ter Heine R, Schuuring E, Timens W, Touw DJ, van Boven JFM, de Langen AJ, Hashemi SMS, Hendriks LEL, Croes S, van den Heuvel MM, Dingemans AC, Mathijssen RHJ, Smit EF, Huitema ADR, Steeghs N, van der Wekken AJ. Therapeutic drug monitoring guided dosing versus standard dosing of alectinib in advanced ALK positive non-small cell lung cancer patients: Study protocol for an international, multicenter phase IV randomized controlled trial (ADAPT ALEC). Front Oncol. 2023 Mar 9;13:1136221. doi: 10.3389/fonc.2023.1136221. eCollection 2023.

  PMID: 36969063 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

alectinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• A.J. van der Wekken, PhD

  University Medical Center Groningen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

M.B. Muntinghe-Wagenaar, Msc

CONTACT

+31503616161; adaptalec@umcg.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The alectinib Cmin for patients treated in arm B (standard dose arm) will be blinded to participants and care providers
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 26, 2022
• First Posted: September 1, 2022
• Study Start: March 23, 2022
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 13, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The study protocol will be available after ending of the study and publication of the manuscript ending 5 years after article publication.
• Access Criteria: For individual participant data meta-analysis

Locations

FR (1); NL (7)