Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Lymphoma

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Lymphosarcoma

Antineoplastic Agents

All Drugs and Chemicals

Crizotinib

patients with ALK rearrangement who started treatment with crizotinib (250 mg twice a day) between the 18/11/2010 and the 31/12/2013 (will include patients from the ATU programs and patients treated after the marketing of crizotinib)

Denis Moro-Sibilot

Michael Duruisseaux

Description of clinical and anatomical features and long-term follow-up for patients with ALK rearrangement and treated by crizotinib

Several French studies on crizotinib have been conducted in recent years. These are not only patients treated in the PROFILE 1005 and 1007 clinical studies but also patients who have been treated with crizotinib in the named patient ATU followed by the cohort ATU (Expended Access Cohort). Under the ATU program and according to ATU regulations, a limited set of data is collected and furthermore the follow up is stopped as soon as the ATU program closes. Thus it is not possible to have access to long term data and post progression data. Our project is to collect data from the patients from the ATU program (named patient and cohort) and if possible patients treated after the marketing of crizotinib, before, during and after crizotinib therapy. Centers selected for this observational study will be those of the IFCT network that took part in the ATU program.

This will allow an accurate analysis of crizotinib therapy under "real life" conditions. It should be emphasized that this information is generally neither available from clinical trials nor from ATU programs.

Description of Clinical Anatomical Features and Long Term Follow-up for Patients With ALK Rearrangements

overall survival post-progression on crizotinib

Incidence of rare and severe complications of crizotinib therapy: hepatotoxicity, interstitial pneumonitis, diastolic heart failure

Intergroupe Francophone de Cancerologie Thoracique

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Amino Acids

Alectinib

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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.

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.

M.B. Muntinghe-Wagenaar, Msc

B. Besse, PhD

M.M. van den Heuvel, PhD

L.E.L. Hendriks, PhD

A.J. de Langen, PhD

S.M.S. Hashemi, Msc

E.F. Smit, PhD

A.C. Dingemans, PhD

A.J. van der Wekken, PhD

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).

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.

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

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

Standard Dosed Alectinib Versus Therapeutic Drug Monitoring Guided Alectinib Dosing

Individual participant data that underlie the results will only be shared upon reasonable request from the Principal Investigator at the UMCG, who will discuss the request with the ADAPT ALEC study team.

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.

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

ORR is the percentage of patients with partial response or complete response, according to RECIST v1.1, of the total treated population.

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

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.

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

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.

Mean change from baseline in EORTC QLQ-C30 and QLQ-LC13 scores

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

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.

Alectinib M4 plasmaconcentrations in relation to alectinib plasma concentrations

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Description of Clinical Anatomical Features and Long Term Follow-up for Patients With ALK Rearrangements	NCT02727335	Non-small Cell ... Anaplastic Lymp...		18 Years -	Intergroupe Francophone de Cancerologie Thoracique
Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels	NCT05525338	Drug Monitoring Carcinoma, Non-... Lung Cancer Anaplastic Lymp... Anaplastic Lymp...	Alectinib	18 Years -	University Medical Center Groningen
Description of Clinical Anatomical Features and Long Term Follow-up for Patients With ALK Rearrangements	NCT02727335	Non-small Cell ... Anaplastic Lymp...		18 Years -	Intergroupe Francophone de Cancerologie Thoracique
Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels	NCT05525338	Drug Monitoring Carcinoma, Non-... Lung Cancer Anaplastic Lymp... Anaplastic Lymp...	Alectinib	18 Years -	University Medical Center Groningen
Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels	NCT05525338	Drug Monitoring Carcinoma, Non-... Lung Cancer Anaplastic Lymp... Anaplastic Lymp...	Alectinib	18 Years -	University Medical Center Groningen

Spots Global Cancer Trial Database for anaplastic lymphoma kinase gene mutation