Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Carboplatin

Pemetrexed

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

Brigatinib 180mg QD (1 x 180mg tablet) until progression

Brigatinib 180mg QD (1 x 180mg tablet) until progression + Carboplatin AUC of 5 mg/mL/min IV infusion every 3 weeks for 4 infusions + pemetrexed 500 mg/m² IV infusion every 3 weeks for 4 infusions

Patients will receive brigatinib orally at a dose of 90 mg QD for a 7 days lead-in period followed by 180 mg QD continuously, with or without food, in 28-day cycles until progression. Dose reductions are possible.

Brigatinib 180 MG

Patients will receive pemetrexed 500 mg/m² followed by carboplatin to target AUC of 5 mg/mL/min both on Day 1 as IV infusion every 3 weeks for 4 infusions. The first infusion of carboplatin and pemetrexed will be administrated at day 8 of brigatinib treatment, at time of dose escalation from 90 mg QD to 180mg QD continuously.

Opérations Cliniques

Marie Capucine WILLEMIN, Dr

Virginie WESTEEL, Pr

Etienne GIROUX LEPRIEUR, Pr

Michael DURUISSEAUX, Dr

Jeannick MADELAINE, Dr

Lise THIBONNIER, Dr

Jean Bernard AULIAC, Dr

Laure FAVIER, Dr

Denis MORO-SIBILOT, Pr

Alexis CORTOT, Pr

Thomas EGENOD, Dr

Aurélie SWALDUZ, Dr

Anne MADROSZYK, Dr

Pascale TOMASINI, Dr

Benoit ROCH, Dr

Didier DEBIEUVRE, Dr

Marie WISLEZ, Pr

Sophie BEAUCAIRE DANEL, Dr

Valérie GOUNANT, Dr

Jacques CADRANEL, Pr

Rémi VEILLON, Dr

Charles RICORDEL, Dr

Florian GUISIER, Dr

Judith RAIMBOURG, Dr

Charles DAYEN, Dr

Céline MASCAUX, Pr

Séverine FRABOULET-MOREAU, Dr

Olivier BYLICKI, Dr

Laurence BIGAY-GAME, Dr

Christelle CLEMENT-DUCHENE, Dr

Luc ODIER, Dr

This is a phase II randomized, open-labelled, non-comparative multicenter study in which ALK+ NSCLC patients who are naïve of treatment for advanced disease will be randomized to receive brigatinib monotherapy (Arm A) or brigatinib and carboplatin-pemetrexed therapy (Arm B). An estimated 110 patients (55 in Arm A, 55 in Arm B) will be enrolled at approximately 30 centers. A safety phase will evaluate the safety of brigatinib with carboplatin and pemetrexed treatment combination (Arm B). The first twenty-six patients enrolled in Arm B will represent the population of the safety phase. Patients will be treated until they experience progressive disease, intolerable toxicity, or another discontinuation criterion is met. Continuation of brigatinib beyond progression is permitted, at the investigator's discretion, if there is evidence of continued clinical benefit. The null hypothesis is progression free survival at 12 months ≤ 69% for Arm B, which is considered not sufficiently clinically meaningful to warrant further study. The alternative hypothesis is that 86% or more of patients in Arm B would achieve progression free survival at 12 months.

Interventional, phase II, randomized, open-labelled, non-comparative multicenter study with two parallel arms

Study of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK)

A Phase II Randomized, Open-Labelled, Multicenter Study of Safety & Efficacy of Combination Brigatinib and Carboplatin-Pemetrexed Therapy or Brigatinib Monotherapy as First-Line Treatment in Advanced ALK-Positive Non-Small Cell Lung Cancer

Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause), determined by investigator assessment.

Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause), determined by independent review.

Proportion of patients who have achieved a best overall response of complete response or partial response (RECIST1.1), determined by investigator assessment and by independent review.

Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).

Proportion of patients who achieved progression free survival (RECIST1.1) with ALK fusion detection in ctDNA baseline liquid biopsy.

Proportion of patients who have achieved a best overall response of complete response or partial response (RECIST1.1) with ALK fusion detection in ctDNA baseline liquid biopsy.

Proportion of patients who have achieved a best overall response of complete response or partial response of the baseline measurable and non-measurable CNS disease (RECIST1.1 + RANO), determined by investigator assessment and by independent review.

Time from enrollment to first observation of progression of the baseline measurable and non-measurable CNS disease (RECIST1.1 + RANA), determined by investigator assessment and by independent review.

Change from baseline of EuroQol Quality of Life 5-Dimension 5-Level Scale (EQ-5D-5L) at all scheduled time points.

The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/QLQ-LC13 questionnaire will be used to determine time until definitive HRQoL score deterioration.

Spots Global Cancer Trial Database for brigatinib 180 mg