NCT02117167

Brief Summary

Open label multicentric randomized phase II trial, using high throughput genome analysis as a therapeutic decision tool, aimed at comparing a targeted treatment administered according to the identified molecular anomalies of the tumor with a standard treatment (pemetrexed in Non-squamous patients and erlotinib in squamous cells, targeted substudy 1) as well as immunotherapy with maintenance therapy in patients without actionable genomic alterations or non eligible to substudy 1 (immune substudy 2).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
999

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2014

Longer than P75 for phase_2

Geographic Reach
1 country

37 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 8, 2014

Completed
9 days until next milestone

First Posted

Study publicly available on registry

April 17, 2014

Completed
6 days until next milestone

Study Start

First participant enrolled

April 23, 2014

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 22, 2018

Completed
4.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2023

Completed
Last Updated

January 10, 2024

Status Verified

January 1, 2024

Enrollment Period

4.7 years

First QC Date

April 8, 2014

Last Update Submit

January 9, 2024

Conditions

Outcome Measures

Primary Outcomes (1)

  • progression-free survival in the targeted drug arm compared to standard maintenance therapy arm

    To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) improves progression-free survival as compared to standard maintenance therapy in patients with metastatic NSCLC

    from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months)

Secondary Outcomes (6)

  • progression-free survival in patients treated with anti-PDL1 antibody (MEDI4736) compared to standard maintenance therapy arm

    from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months)

  • overall survival in each substudy

    from randomization to death (any cause), up to 16 months

  • overall response rates and changes in tumor size in each substudy

    tumor response is assessed every 21 days from treatment initiation until first progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months)

  • evaluate safety, in each substudy

    toxicities will be assessed during the whole treatment period (4 months expected in average) followed by a 1-year post-treatment follow-up period, and reported during the visits scheduled by the study flow chart

  • efficacy (response rate, change in tumor size, progression-free survival, overall survival) and safety of each individual targeted agent (substudy 1)

    tumor response is assessed every 21 days from treatment initiation until first progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months)

  • +1 more secondary outcomes

Study Arms (4)

Substudy 1: targeted agent

EXPERIMENTAL

Arm A1/ targeted arm: targeted maintenance from a list of targeted drugs guided by the genomic analysis, AZD2014 tablet per os 50 mg bd, continuous dosing, AZD4547 tablet per os 80 mg bd, 2 weeks on/1 week off, AZD5363 capsule per os 480 mg bd, 4 days on/3 days off, AZD8931 tablet per os 40 mg bd, continuous dosing, selumetinib capsule per os 75 mg bd, continuous dosing, vandetanib tablet per os 300 mg od, continuous dosing, olaparib tablet per os 300 mg bd continuous dosing savolitinib tablet per os 600 mg od continuous dosing

Drug: AZD2014Drug: AZD4547Drug: AZD5363Drug: AZD8931Drug: SelumetinibDrug: VandetanibDrug: savolitinibDrug: Olaparib

Substudy 1: standard maintenance therapy

ACTIVE COMPARATOR

Arm B1/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice

Drug: Standard maintenance for squamous NSCLCDrug: Pemetrexed

Substudy 2: Immunotherapy

EXPERIMENTAL

Arm A2/ Immunotherapy arm: maintenance with durvalumab for patient without actionable genomic alterations or non eligible to Targeted substudy 1, durvalumab Intra-venous 10 mg/kg, Q2W

Drug: Durvalumab

Substudy 2: standard maintenance therapy

ACTIVE COMPARATOR

Arm B2/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice

Drug: Standard maintenance for squamous NSCLCDrug: Pemetrexed

Interventions

Target: m-TOR

Substudy 1: targeted agent

Target: FGFR

Substudy 1: targeted agent

Target: AKT

Substudy 1: targeted agent

Target: HER2, EGFR

Substudy 1: targeted agent

Target: MEK

Also known as: ARRY-142866
Substudy 1: targeted agent

Target : VEGF, EGFR

Also known as: CAPRELSA
Substudy 1: targeted agent
Substudy 1: standard maintenance therapySubstudy 2: standard maintenance therapy

Standard maintenance for non squamous NSCLC

Also known as: ALIMTA
Substudy 1: standard maintenance therapySubstudy 2: standard maintenance therapy

Target: PD-L1

Substudy 2: Immunotherapy

target : MET

Substudy 1: targeted agent

target : PARP

Also known as: LYNPARZA
Substudy 1: targeted agent

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • histologically proven NSCLC
  • Metastatic relapse or stage IV at diagnosis, or stage IIIb not amenable to surgery or radiotherapy
  • No EGFR-activating mutation or ALK translocation
  • primary tumor or metastases that can be biopsied, excluding bone.
  • Age \>18 years
  • WHO Performance Status 0/1
  • Chemo-naïve patients eligible to a first line platinum-based chemotherapy
  • No tumor progression observed with the current line of treatment
  • measurable target lesion or evaluable diseases RECIST

You may not qualify if:

  • Spinal cord compression and/or symptomatic or progressive brain metastases
  • Abnormal coagulation contraindicating biopsy
  • Inability to swallow
  • Major problem with intestinal absorption
  • Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG
  • Any factors increasing the risk of QTc prolongation or arrhythmic events
  • Experience of any of the following in the preceding 12 months: coronary artery bypass graft, angioplasty, vascular stent, myocardial infarction, past or current uncontrolled angina pectoris, congestive heart failure NYHA Grade ≥2, torsades de pointes, current uncontrolled hypertension, cardiomyopathy
  • Past medical history of interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which requires steroid treatment or any evidence of clinically interstitial lung disease
  • Previous or current malignancies of other histologies within the last 5 years,
  • Evidence of severe or uncontrolled systemic disease (active bleeding diatheses, or active Hepatitis B, C and HIV)
  • Diagnosis of diabetes mellitus type I or II
  • diagnosis of acne rosacea, severe psoriasis and severe atopic eczema
  • Prior exposure to anthracyclines or mitoxantrone with cumulative exposure in excess of 360 mg/m² for doxorubicin, 720 mg/m² for epirubicin, or 72 mg/m² for mitoxantrone
  • History of retinal degenerative disease, eye injury or corneal surgery in the previous 3 months, past history of central serous retinopathy or retinal vein occlusion, intraocular pressure \>21 mmHg, or uncontrolled glaucoma.
  • History of hemorrhagic or thrombotic stroke, TIA or other CNS bleeds
  • +31 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (37)

Centre Hospitalier Henri Duffau

Avignon, France

Location

Centre Hospitalier Universitaire de Besancon - Hopital Jean Minjoz

Besançon, France

Location

Hôpital Avicenne

Bobigny, France

Location

Institut Bergonié

Bordeaux, France

Location

Hôpital Ambroise Paré

Boulogne-Billancourt, France

Location

Hospices Civils de Lyon- Hôpital Louis Pradel

Bron, France

Location

Centre François Baclesse

Caen, France

Location

CHU Caen

Caen, France

Location

Chu de Caen - Hopital Cote de Nacre

Caen, France

Location

Hôpital Louis Pasteur

Chartres, France

Location

centre Jean Perrin

Clermont-Ferrand, France

Location

CHU Clermont Ferrand - Hôpital Gabriel Montpied

Clermont-Ferrand, France

Location

Hopitaux Civils de Colmar

Colmar, France

Location

Centre Hopsitalier Intercommunal de Créteil

Créteil, France

Location

Centre Georges François Leclerc

Dijon, France

Location

CHU Grenoble

Grenoble, France

Location

Chd Vendee

La Roche-sur-Yon, France

Location

CH du Mans

Le Mans, France

Location

Centre Oscar Lambret

Lille, France

Location

CHRU de Lille

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital Nord

Marseille, France

Location

Institut Paoli Calmettes

Marseille, France

Location

Institut de cancérologie de l'Ouest

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Chr Orleans

Orléans, France

Location

AH-HP Hôpital Saint Louis

Paris, France

Location

AP-HP Hôpital Cochin

Paris, France

Location

AP-HP Hôpital Tenon

Paris, France

Location

Institut Curie

Paris, France

Location

Centre Hospitalier de Pau

Pau, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, France

Location

Chru Strasbourg - Nouvel Hopital Civil

Strasbourg, France

Location

CHI de Toulon - Hôpital Sainte-Musse

Toulon, France

Location

CHU Toulouse -Hôpital Larrey

Toulouse, France

Location

Hôpital Bretonneau

Tours, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (1)

  • Middleton G, Crack LR, Popat S, Swanton C, Hollingsworth SJ, Buller R, Walker I, Carr TH, Wherton D, Billingham LJ. The National Lung Matrix Trial: translating the biology of stratification in advanced non-small-cell lung cancer. Ann Oncol. 2015 Dec;26(12):2464-9. doi: 10.1093/annonc/mdv394. Epub 2015 Sep 25.

Related Links

MeSH Terms

Interventions

vistusertibAZD4547capivasertibAZD 8931AZD 6244vandetanibPemetrexeddurvalumab1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazineolaparib

Intervention Hierarchy (Ancestors)

GuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Dicarboxylic

Study Officials

  • Fabrice BARLESI, Pr

    CHU Hopital Nord Marseille

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 8, 2014

First Posted

April 17, 2014

Study Start

April 23, 2014

Primary Completion

December 22, 2018

Study Completion

December 1, 2023

Last Updated

January 10, 2024

Record last verified: 2024-01

Locations