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

NCT ID: NCT05525338

Last Updated: 2024-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

196 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-23

Study Completion Date

2026-12-31

Brief Summary

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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

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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).

Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

The alectinib Cmin for patients treated in arm B (standard dose arm) will be blinded to participants and care providers

Study Groups

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TDM-guided dosing arm

Group Type EXPERIMENTAL

Alectinib

Intervention Type 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.

Standard dose arm

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.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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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.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amsterdam University Medical Center

OTHER

Sponsor Role collaborator

Erasmus Medical Center

OTHER

Sponsor Role collaborator

Maastricht University Medical Center

OTHER

Sponsor Role collaborator

Radboud University Medical Center

OTHER

Sponsor Role collaborator

The Netherlands Cancer Institute

OTHER

Sponsor Role collaborator

Leiden University Medical Center

OTHER

Sponsor Role collaborator

University Medical Center Groningen

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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A.J. van der Wekken, PhD

Role: PRINCIPAL_INVESTIGATOR

University Medical Center Groningen

Locations

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Gustave Roussy

Villejuif, Val-de-Marne, France

Site Status NOT_YET_RECRUITING

Radboud University Medical Center

Nijmegen, Gelderland, Netherlands

Site Status RECRUITING

Maastricht University Medical Center +

Maastricht, Limburg, Netherlands

Site Status RECRUITING

The Netherlands Cancer Institute

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

Amsterdam University Medical Center

Amsterdam, North Holland, Netherlands

Site Status RECRUITING

Leiden University Medical Center

Leiden, South Holland, Netherlands

Site Status RECRUITING

Erasmus Medical Center

Rotterdam, South Holland, Netherlands

Site Status RECRUITING

University Medical Center Groningen

Groningen, , Netherlands

Site Status RECRUITING

Countries

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France Netherlands

Central Contacts

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M.B. Muntinghe-Wagenaar, Msc

Role: CONTACT

+31503616161

Facility Contacts

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B. Besse, PhD

Role: primary

M.M. van den Heuvel, PhD

Role: primary

L.E.L. Hendriks, PhD

Role: primary

A.J. de Langen, PhD

Role: primary

S.M.S. Hashemi, Msc

Role: primary

E.F. Smit, PhD

Role: primary

A.C. Dingemans, PhD

Role: primary

A.J. van der Wekken, PhD

Role: primary

References

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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.

Reference Type DERIVED
PMID: 36969063 (View on PubMed)

Other Identifiers

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2020-001737-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

NL9411

Identifier Type: REGISTRY

Identifier Source: secondary_id

202000251

Identifier Type: -

Identifier Source: org_study_id

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