Osimertinib Treatment on EGFR T790M Plasma Positive NSCLC Patients (APPLE)

Phase 2

Active, not recruiting

• Conditions: NSCLC
• Interventions: Drug: Osimertinib; Drug: Gefitinib

• Registration Number: NCT02856893
• Lead Sponsor: European Organisation for Research and Treatment of Cancer - EORTC

Brief Summary

The phase II APPLE trial gives the opportunity to prospectively validate liquid biopsies as a new standard for testing tumor progression compared with conventional radiological procedure in EGFR mutant advanced NSCLC patients. Moreover based on the sequential T790M test during treatment the investigators will assess the predictive value of liquid biopsies. APPLE trial will examine the best strategy for delivering osimertinib (upfront versus sequential treatment after 1st generation EGFR TKI) in EGFR mutant NSCLC patients. Finally, the trial will also explore the mechanisms of acquired resistance to Osimertinib based on the results of an optional biopsy upon progression.

Detailed Description

Primary objective To evaluate the best strategy for delivering Osimertinib (AZD9291) in NSCLC patients with EGFR mutation. The objective is assessed by Progression Free Survival rate at 18 months (PFS-18).

Secondary objectives

* To evaluate PFS on Osimertinib measured from randomization by RECIST criteria 1.1 \[Ref 33\].

* To evaluate PFS measured from switching to Osimertinib by RECIST criteria 1.1 \[Ref 33\].

* To determine the proportion of patients receiving Osimertinib based on the determination of cfDNA T790M mutation positive.

* To evaluate time to symptomatic brain metastases in patients with presence of brain metastases at study entry.

* To evaluate PFS-2 (defined as the sum of the PFS to Gefitinib and the PFS to Osimertinib treatment).

* To evaluate Overall Response Rate (ORR) to Osimertinib.

* To evaluate the Treatment duration.

* To evaluate Time to progression (TTP) on Osimertinib (measured from switching to osimertinib).

* To evaluate Overall Survival (OS).

* To evaluate time to brain progression (TTBP).

* Safety.

Study Timeline

• Study First Submitted: 2016-07-11
• Study First Submitted QC: 2016-08-04
• Study First Posted: 2016-08-05
• Study Start: 2017-10-10
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-13
• Last Update Posted: 2022-09-15
• Primary Completion: 2023-02
• Study Completion: 2027-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 156

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Osimertinib till progression	Osimertinib	Osimertinib until PD according to RECIST 1.1
Gefitinib till + blood test/progression than Osimertinib	Osimertinib	Gefitinib until emergence of positive T790M status ("cfDNA T790M positive progression") followed by Osimertinib until second PD according to RECIST 1.1
Gefitinib till progression than Osimertinib	Osimertinib	Gefitinib until PD according to RECIST 1.1 followed by Osimertinib until PD according to RECIST 1.1
Gefitinib till + blood test/progression than Osimertinib	Gefitinib	Gefitinib until emergence of positive T790M status ("cfDNA T790M positive progression") followed by Osimertinib until second PD according to RECIST 1.1
Gefitinib till progression than Osimertinib	Gefitinib	Gefitinib until PD according to RECIST 1.1 followed by Osimertinib until PD according to RECIST 1.1

Primary Outcome Measures

Name	Time	Method
PFS Rate at 18 months	24 months after first patient in

Secondary Outcome Measures

Name	Time	Method
Safety	24 months after first patient in	Number of participants with treatment-related adverse events by CTCAE version 4.0. Adverse events, serious adverse events and adverse reactions will be monitored.
Overall Response Rate (ORR) to Osimertinib	24 months after first patient in
Overall Survival (OS)	24 months after first patient in
Time to progression on Osimertinib	through study completion
PFS measured from switching to Osimertinib by RECIST criteria 1.1	24 months after first patient in
Proportion of patients receiving Osimertinib based on the determination of cfDNA T790M mutation positive	24 months after first patient in
Time to brain progression (TTBP)	24 months after first patient in
Time to symptomatic brain metastases in patients with presence of brain metastases at study entry	24 months after first patient in
Treatment duration	24 months after first patient in

Trial Locations

Locations (22)

CHU de Brest; 🇫🇷 Brest, France

Medical University of Gdansk; 🇵🇱 Gdansk, Poland

Institut Paoli-Calmettes; 🇫🇷 Marseille, France

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Institut Bergonie; 🇫🇷 Bordeaux, France

Centre Francois Baclesse; 🇫🇷 Caen, France

Centre Hopitalier Intercommunal De Creteil; 🇫🇷 Créteil, France

Centre Paul Strauss; 🇫🇷 Strasbourg, France

CHU Toulouse - Hopital Larrey; 🇫🇷 Toulouse, France

Assistance Publique - Hopitaux de Marseille - Hopital Nord; 🇫🇷 Marseille, France

Institut de Cancerologie de Lorraine; 🇫🇷 Vandœuvre-lès-Nancy, France

Gustave Roussy; 🇫🇷 Villejuif, France

King Hussein Cancer Center; 🇯🇴 Amman, Jordan

University Clinic Golnik; 🇸🇮 Golnik, Slovenia

The Institute Of Oncology; 🇸🇮 Ljubljana, Slovenia

Vall d'Hebron Institut d'Oncologia; 🇪🇸 Barcelona, Spain

Hospital De La Santa Creu I Sant Pau; 🇪🇸 Barcelona, Spain

University Hospital A Coruna-Hospital Teresa Herrera; 🇪🇸 Coruna, Spain

Hospital Clinic Universitari de Barcelona; 🇪🇸 Barcelona, Spain

Institut Catala d'Oncologia - ICO Badalona - Hospital De Mataro; 🇪🇸 Mataró, Spain

Virgen del Rocio University Hospital; 🇪🇸 Sevilla, Spain

Hospital Universitario 12 De Octubre; 🇪🇸 Madrid, Spain