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SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profils in Metastatic NSCLC Patients (SAFIR02_Lung)

This study is currently recruiting participants.
Verified May 2017 by UNICANCER
Sponsor:
ClinicalTrials.gov Identifier:
NCT02117167
First Posted: April 17, 2014
Last Update Posted: May 5, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborators:
IFCT
Fondation ARC
AstraZeneca
Information provided by (Responsible Party):
UNICANCER
  Purpose
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).

Condition Intervention Phase
Non-small Cell Lung Cancer Metastatic Drug: AZD2014 Drug: AZD4547 Drug: AZD5363 Drug: AZD8931 Drug: Selumetinib Drug: Vandetanib Drug: Standard maintenance for squamous NSCLC Drug: Pemetrexed Drug: MEDI4736 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Intergroup Trial UNICANCER UC 0105-1305/ IFCT 1301: SAFIR02_Lung - Evaluation of the Efficacy of High Throughput Genome Analysis as a Therapeutic Decision Tool for Patients With Metastatic Non-small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • progression-free survival in the targeted drug arm compared to standard maintenance therapy arm [ Time Frame: from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months) ]
    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


Secondary Outcome Measures:
  • progression-free survival in patients treated with anti-PDL1 antibody (MEDI4736) compared to standard maintenance therapy arm [ Time Frame: from randomization to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months) ]
    To evaluate whether treatment with MEDI4736 improves progression-free survival as compared to standard maintenance therapy in patients with metastatic NSCLC

  • overall survival in each substudy [ Time Frame: from randomization to death (any cause), up to 16 months ]
    To evaluate whether treatment with targeted agents guided by high throughput molecular analysis (CGH array, next generation sequencing) or MEDI4736 improves overall survival as compared to standard maintenance therapy in patients with metastatic NSCLC

  • overall response rates and changes in tumor size in each substudy [ Time Frame: 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) ]
    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

  • evaluate safety, in each substudy [ Time Frame: 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 ]
    Toxicities are graded according to the CTCAE V4

  • efficacy (response rate, change in tumor size, progression-free survival, overall survival) and safety of each individual targeted agent (substudy 1) [ Time Frame: 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) ]
    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

  • correlate molecular characteristics in patients with the efficacy endpoints (response rate, progression-free and overall survival) in each substudy [ Time Frame: from randomization or treatment initiation to disease progression or death from any cause, whichever comes first, up to 16 months (estimated treatment duration average: 4 months) ]
    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria


Estimated Enrollment: 650
Actual Study Start Date: April 23, 2014
Estimated Study Completion Date: February 2022
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Substudy 1: targeted agent
Arm A1/ targeted arm: targeted maintenance from a list of 6 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,
Drug: AZD2014
Target: m-TOR
Drug: AZD4547
Target: FGFR
Drug: AZD5363
Target: AKT
Drug: AZD8931
Target: HER2, EGFR
Drug: Selumetinib
Target: MEK
Other Name: ARRY-142866
Drug: Vandetanib
Target : VEGF, EGFR
Other Name: CAPRELSA
Active Comparator: Substudy 1: standard maintenance therapy
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 NSCLC Drug: Pemetrexed
Standard maintenance for non squamous NSCLC
Other Name: ALIMTA
Experimental: Substudy 2: Immunotherapy
Arm A2/ Immunotherapy arm: maintenance with MEDI4736 for patient without actionable genomic alterations or non eligible to Targeted substudy 1, MEDI4736 Intra-venous 10 mg/kg, Q2W
Drug: MEDI4736
Target: PD-L1
Active Comparator: Substudy 2: standard maintenance therapy
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 NSCLC Drug: Pemetrexed
Standard maintenance for non squamous NSCLC
Other Name: ALIMTA

Detailed Description:

Screening phase:

New frozen biopsy or an archived frozen sample or ctDNA sample will be sent to the genomic plateforms for DNA extraction and genomic analysis (DNA microarrays and Next generation sequencing).

Patients can be considered as pre-eligible for the targeted substudy 1 randomisation phase when both following mandatory conditions have been met : stable or responding disease has been observed after 4 cycles of chemotherapy (investigator judgment) and targetable alteration has been identified by the Molecular tumor board (MTB).

If not eligible for the substudy 1 randomisation phase, patients can be considered as pre-eligible for the immune substudy 2 randomization phase when both following mandatory conditions are met: stable or responding disease (investigator judgment) is observed after 4 cycles of a platinum-based chemotherapy AND not eligible to randomization in the substudy 1 (because patient had no targetable alteration identified by the Molecular Tumor Board, or failed to have a genomic profile for the tumor [low tumor cells percentage, technical issue during genomic analysis, etc.], or a non-inclusion criteria that precluded entry into the substudy 1)

Randomization phase:

The mandatory post-chemotherapy 28-day wash-out period following cycle 4 of chemotherapy will provide time to achieve all the required tests and examinations.

The randomization program will allocate the following treatments with a 2:1 ratio in favor of Arm A of the considered substudy:

Substudy 1 : targeted therapies versus standard maintenance therapy

  • Arm A1 / targeted arm: targeted maintenance from a list of 6 targeted drugs guided by the genomic analysis, or
  • Arm B1 / standard arm : standard maintenance (pemetrexed in non-squamous and standard practice in squamous NSCLC).

Substudy 2 : immunotherapy versus standard maintenance therapy

  • Arm A2 / immunotherapy maintenance arm: MEDI4736 or
  • Arm B2 / standard arm : standard maintenance (pemetrexed in non-squamous and standard practice in squamous NSCLC).
  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Screening phase:

Inclusion Criteria:

  • 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

Exclusion criteria

  • 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 heamorrhagic or thrombotic stroke, TIA or other CNS bleeds
  • Renal disease including glomerulonephritis, nephritic syndrome, Fanconi syndrome, renal tubular acidosis
  • Patients using drugs that are known potent inhibitors or potent inducers or substrates of cytochrome P450

Randomized phase:

Substudy 1:

Inclusion criteria

  • Patients who received 4 cycles of an induction platinum-based chemotherapy and who have a SD or a PR at randomization
  • presenting at least one genomic alteration from the predefined list
  • Age > 25 years for patients planned to receive AZD4547
  • 28-day washout period from chemo prior to randomization and grade ≤1 residual toxicities

Exclusion criteria

  • Life expectancy < 3 months
  • Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the platinium based chemotherapy before 4 full cycles have been delivered
  • Less than 28 days from radiotherapy, less than 2 weeks from palliative radiation
  • Patients previously treated with a targeted agent in the same class as agents tested in this study
  • Toxicities of grade ≥2 from any previous anti-cancer therapy
  • Altered haematopoietic or organ function
  • Mean resting corrected QT interval (QTc)>480msec (or QTcF >450 msec) obtained from 3 consecutive ECGs
  • LVEF <55% (MUGA scan or Echocardiogram),
  • Altered ophthalmic conditions confirmed by an ophthalmology specialist for patients likely to be treated with AZD4547 orAZD8931 or Selumetinib
  • Patients using non-substitutable drugs, that are known to prolong QT interval or induce Torsades de Pointes, when they are supposed to be treated with vandetanib, AZD5363 or AZD8931

Substudy 2:

Inclusion criteria

  • Patients who received 4 cycles of an induction platinum-based chemotherapy and who have a SD or a PR at randomization
  • Patients not eligible to substudy 1
  • 28-day washout period from chemo prior to randomization and grade ≤1 residual toxicities

Exclusion criteria

  • Life expectancy < 3 months
  • Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the platinium based chemotherapy before 4 full cycles have been delivered
  • Any previous treatment with a PD1 or PD-L1 inhibitor, including MEDI4736
  • Toxicities of grade ≥2 from any previous anti-cancer therapy
  • Altered haematopoietic or organ function
  • Mean resting QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 consecutive ECGs using Bazett's Correction
  • Current or prior use of immunosuppressive medication within 28 days before the first dose of MEDI4736, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid
  • Active or prior documented autoimmune disease within the past 2 years NOTE: Subjects with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded
  • History of primary immunodeficiency
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02117167


Contacts
Contact: Alexandra JACQUET, Ms + 33 1 73 77 55 45 a-jacquet@unicancer.fr

Locations
France
Centre Hospitalier Henri Duffau Recruiting
Avignon, France
Contact: Nicolas CLOAREC, MD       nicolas.cloarec@ch-avignon.fr   
Principal Investigator: Nicolas CLOAREC, MD         
Centre Hospitalier Universitaire de Besancon - Hopital Jean Minjoz Not yet recruiting
Besancon, France
Contact: Virginie WESTEEL, MD       virginie.westeel@univ.fcomte.fr   
Principal Investigator: Virginie WESTEEL, MD         
Hôpital Avicenne Not yet recruiting
Bobigny, France
Contact: Boris DUCHEMANN, MD       boris.duchemann@aphp.fr   
Principal Investigator: Boris DUCHEMANN, MD         
Institut Bergonié Recruiting
Bordeaux, France
Contact: François Chomy, MD       f.chomy@bordeaux.unicancer.fr   
Principal Investigator: François Chomy, MD         
Hôpital Ambroise Paré Not yet recruiting
Boulogne Billancourt, France
Contact: Etienne GIROUX LEPRIEUR, MD       etienne.giroux-leprieur@aphp.fr   
Principal Investigator: Etienne GIROUX LEPRIEUR, MD         
Hospices Civils de Lyon- Hôpital Louis Pradel Not yet recruiting
Bron, France
Contact: Nicolas Girard, MD       nicolas.girard@chu-lyon.fr   
Principal Investigator: Nicolas Girard, MD         
Centre François Baclesse Recruiting
Caen, France
Contact: Radj Gervais, MD       r.gervais@baclesse.unicancer.fr   
Principal Investigator: Radj Gervais, MD         
CHU Caen Recruiting
Caen, France
Contact: Gérard Zalcman, MD       zalcman-g@chu-caen.fr   
Principal Investigator: Gérard Zalcman, MD         
Chu de Caen - Hopital Cote de Nacre Not yet recruiting
Caen, France
Contact: Jeannick MADELAINE, MD       madelaine-j@chu-caen.fr   
Principal Investigator: Jeannick MADELAINE, MD         
Hôpital Louis Pasteur Recruiting
Chartres, France
Contact: Claire Lethrosne, MD       clethrosne@ch-chartres.fr   
Principal Investigator: Claire Lethrosne, MD         
centre Jean Perrin Not yet recruiting
Clermont-Ferrand, France
Contact: Xavier Durando, MD       xavier.durando@cjp.fr   
Principal Investigator: Xavier Durando, MD         
CHU Clermont Ferrand - Hôpital Gabriel Montpied Recruiting
Clermont-Ferrand, France
Contact: Henri Janicot, MD       hjanicot@chu-clermontferrand.fr   
Principal Investigator: Henri Janicot, MD         
Hopitaux Civils de Colmar Not yet recruiting
Colmar, France
Contact: Lionel MOREAU, MD       lionel.moreau@ch-colmar.fr   
Principal Investigator: Lionel MOREAU, MD         
Centre Hopsitalier Intercommunal de Créteil Recruiting
Créteil, France
Contact: Isabelle Monnet, MD       isabelle.monnet@chicreteil.fr   
Principal Investigator: Isabelle Monnet, MD         
Centre Georges François Leclerc Recruiting
Dijon, France
Contact: Bruno Coudert, MD       bcoudert@cgfl.fr   
Principal Investigator: Bruno Coudert, MD         
CHU Grenoble Recruiting
Grenoble, France
Contact: Denis Moro-Sibilot, MD       Dmoro-Sibilot@chu-grenoble.fr   
Principal Investigator: Denis Moro-Sibilot, MD         
Chd Vendee Not yet recruiting
La Roche Sur Yon, France
Contact: Marie MARCQ, MD       marie.marcq@chd-vendee.fr   
Principal Investigator: Marie MARCQ, MD         
CH du Mans Not yet recruiting
Le Mans, France
Contact: Olivier Molinier, MD       omolinier@ch-lemans.fr   
Principal Investigator: Olivier Molinier, MD         
Centre Oscar Lambret Recruiting
Lille, France
Contact: Eric Dansin, MD       e-dansin@o-lambret.fr   
Principal Investigator: Eric Dansin, MD         
CHRU de Lille Recruiting
Lille, France
Contact: Alexis Cortot, MD       Alexis.CORTOT@CHRU-LILLE.FR   
Principal Investigator: Alexis Cortot, MD         
Centre Léon Bérard Recruiting
Lyon, France
Contact: Maurice Pérol, MD       maurice.perol@lyon.unicancer.fr   
Principal Investigator: Maurice Pérol, MD         
Hôpital Nord Recruiting
Marseille, France
Contact: Fabrice Barlesi, MD       fabrice.barlesi@ap-hm.fr   
Principal Investigator: Fabrice Barlési, MD         
Institut Paoli Calmettes Not yet recruiting
Marseille, France
Contact: Anne MADROSZYK, MD       madroszyka@ipc.unicancer.fr   
Principal Investigator: Anne MADROSZYK, MD         
Institut de cancérologie de l'Ouest Recruiting
Nantes, France
Contact: Jaafar Bennouna, MD       jaafar.bennouna@ico.unicancer.fr   
Principal Investigator: Jaafar Bennouna, MD         
Centre Antoine Lacassagne Not yet recruiting
Nice, France
Contact: Josiane OTTO, MD       josiane.otto@nice.unicancer.fr   
Principal Investigator: Josiane OTTO, MD         
Chr Orleans Not yet recruiting
Orleans, France
Contact: Hugues MOREL, MD       hugues.morel@chr-orleans.fr   
Contact: , MD         
Principal Investigator: Hugues MOREL         
AH-HP Hôpital Saint Louis Recruiting
Paris, France
Contact: Damien Pouessel, MD       damien.pouessel@sls.aphp.fr   
Principal Investigator: Damien Pouessel, MD         
AP-HP Hôpital Cochin Recruiting
Paris, France
Contact: Jeanne Chapron, MD       jeanne.chapron@cch.aphp.fr   
Principal Investigator: Jeanne Chapron, MD         
AP-HP Hôpital Européen Georges Pompidou Withdrawn
Paris, France
AP-HP Hôpital Tenon Recruiting
Paris, France
Contact: Marie Wislez, MD       marie.wislez@tnn.aphp.fr   
Principal Investigator: Marie Wislez, MD         
Institut Curie Recruiting
Paris, France
Contact: Catherine Daniel, MD       catherine.daniel@curie.fr   
Principal Investigator: Catherine Daniel, MD         
Centre Hospitalier de Pau Not yet recruiting
PAU, France
Contact: Aldo RENAULT, MD       aldo.renault@ch-pau.fr   
Principal Investigator: Aldo RENAULT, MD         
Centre Hospitalier Lyon Sud Recruiting
Pierre Bénite, France
Contact: Jean-Pierre Souquet, MD       pierre-jean.souquet@chu-lyon.fr   
Principal Investigator: Jean-Pierre Souquet, MD         
CHR Pontchailloux Not yet recruiting
Rennes, France
Contact: Hervé Léna, MD       herve.lena@chu-rennes.fr   
Principal Investigator: Hervé Léna, MD         
Chru Strasbourg - Nouvel Hopital Civil Not yet recruiting
Strasbourg, France
Contact: Charlotte LEDUC, MD         
Contact: charlotte.leduc@chru-strasbourg.fr         
Principal Investigator: Charlotte LEDUC, MD         
CHI de Toulon - Hôpital Sainte-Musse Recruiting
Toulon, France
Contact: Clarisse Audigier Valette, MD       clarisse.audigier-valette@orange.fr   
Principal Investigator: Clarisse Audigier Valette, MD         
CHU Toulouse -Hôpital Larrey Recruiting
Toulouse, France
Contact: Julien Mazières, MD       mazieres.j@chu-toulouse.fr   
Principal Investigator: Julien Mazières, MD         
Hôpital Bretonneau Recruiting
Tours, France
Contact: Eric Pichon, MD       e.pichon@chu-tours.fr   
Principal Investigator: Eric Pichon, MD         
Gustave Roussy Recruiting
Villejuif, France
Contact: Benjamin Besse, MD       Benjamin.BESSE@gustaveroussy.fr   
Principal Investigator: Benjamin Besse, MD         
Sub-Investigator: Jean-Charles Soria, MD         
Sponsors and Collaborators
UNICANCER
IFCT
Fondation ARC
AstraZeneca
Investigators
Principal Investigator: Jean-Charles SORIA, Pr Gustave Roussy Villejuif
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT02117167     History of Changes
Other Study ID Numbers: UC 0105-1305 / IFCT 1301
2013-001653-27 ( EudraCT Number )
First Submitted: April 8, 2014
First Posted: April 17, 2014
Last Update Posted: May 5, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Pemetrexed
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors