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Non-small Cell Lung Cancer MetastaticPhase 2SAFIR02_LungNCT02117167

SAFIR02_Lung - Efficacy of Targeted Drugs Guided by Genomic Profiles in Metastatic NSCLC Patients

A Phase 2 study testing AZD2014, AZD4547 and AZD5363 in people with Non-small Cell Lung Cancer Metastatic, run by UNICANCER at 37 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non-small Cell Lung Cancer Metastatic
What is being tested?
AZD2014, AZD4547 and AZD5363
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
999 participants
Where
37 sitesFrance
Study dates
23 Apr 2014to Dec 2023
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 16Show fewer
  • 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
  • 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
  • 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

Who cannot join

  • 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
Show all 39Show fewer
  • 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
  • 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:
  • Life expectancy <3 months
  • Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the platinum-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
  • Left ventricular ejection fraction (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:
  • Life expectancy <3 months
  • Disease progression occuring at any time during chemotherapy and before randomization or toxicity that led to the discontinuation of the platinum-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

Trial locations and contacts

37 sites in 1 country.

37 sites in 1 country

France37 sites

  • Centre Hospitalier Henri Duffau

    Avignon

  • Centre Hospitalier Universitaire de Besancon - Hopital Jean Minjoz

    Besançon

  • Hôpital Avicenne

    Bobigny

  • Institut Bergonié

    Bordeaux

  • Hôpital Ambroise Paré

    Boulogne-Billancourt

  • Hospices Civils de Lyon- Hôpital Louis Pradel

    Bron

  • Centre François Baclesse

    Caen

  • CHU Caen

    Caen

  • Chu de Caen - Hopital Cote de Nacre

    Caen

  • Hôpital Louis Pasteur

    Chartres

  • centre Jean Perrin

    Clermont-Ferrand

  • CHU Clermont Ferrand - Hôpital Gabriel Montpied

    Clermont-Ferrand

  • Hopitaux Civils de Colmar

    Colmar

  • Centre Hopsitalier Intercommunal de Créteil

    Créteil

  • Centre Georges François Leclerc

    Dijon

  • CHU Grenoble

    Grenoble

  • Chd Vendee

    La Roche-sur-Yon

  • CH du Mans

    Le Mans

  • Centre Oscar Lambret

    Lille

  • CHRU de Lille

    Lille

  • Centre Léon Bérard

    Lyon

  • Hôpital Nord

    Marseille

  • Institut Paoli Calmettes

    Marseille

  • Institut de cancérologie de l'Ouest

    Nantes

  • Centre Antoine Lacassagne

    Nice

  • Chr Orleans

    Orléans

  • AH-HP Hôpital Saint Louis

    Paris

  • AP-HP Hôpital Cochin

    Paris

  • AP-HP Hôpital Tenon

    Paris

  • Institut Curie

    Paris

  • Centre Hospitalier de Pau

    Pau

  • Centre Hospitalier Lyon Sud

    Pierre-Bénite

  • Chru Strasbourg - Nouvel Hopital Civil

    Strasbourg

  • CHI de Toulon - Hôpital Sainte-Musse

    Toulon

  • CHU Toulouse -Hôpital Larrey

    Toulouse

  • Hôpital Bretonneau

    Tours

  • Gustave Roussy

    Villejuif

Other trials in France

About this study

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

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).

Read the detailed description

Screening phase:

New frozen biopsy or an archived frozen sample or ctDNA sample will be sent to the genomic platforms 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).
Being tested
AZD2014, AZD4547, AZD5363, AZD8931, Selumetinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AZD2014Drug

    Target: m-TOR

  • AZD4547Drug

    Target: FGFR

  • AZD5363Drug

    Target: AKT

  • AZD8931Drug

    Target: HER2, EGFR

  • SelumetinibDrug

    Also called ARRY-142866

    Target: MEK

  • VandetanibDrug

    Also called CAPRELSA

    Target : VEGF, EGFR

  • Standard maintenance for squamous NSCLCDrug

  • PemetrexedDrug

    Also called ALIMTA

    Standard maintenance for non squamous NSCLC

  • DurvalumabDrug

    Target: PD-L1

  • savolitinibDrug

    target : MET

  • OlaparibDrug

    Also called LYNPARZA

    target : PARP

Study groups in NCT02117167
Study groupRoleWhat they receive
Substudy 1: targeted agentExperimentalArm 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
Receives: Drug: AZD2014; Drug: AZD4547; Drug: AZD5363; Drug: AZD8931; Drug: Selumetinib; Drug: Vandetanib; Drug: savolitinib; Drug: Olaparib
Substudy 1: standard maintenance therapyActive comparatorArm B1/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice
Receives: Drug: Standard maintenance for squamous NSCLC; Drug: Pemetrexed
Substudy 2: ImmunotherapyExperimentalArm 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
Receives: Drug: Durvalumab
Substudy 2: standard maintenance therapyActive comparatorArm B2/ standard arm pemetrexed Intra venous 500 mg/m², every 3 weeks, standard maintenance left to the investigator's choice
Receives: Drug: Standard maintenance for squamous NSCLC; Drug: Pemetrexed

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 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)

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

    To evaluate whether treatment with MEDI4736 improves progression-free survival as compared to standard maintenance therapy in patients with metastatic NSCLC

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

  2. overall survival in each substudy

    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

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

  3. overall response rates and changes in tumor size in each substudy

    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

    Measured: 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)

  4. evaluate safety, in each substudy

    Toxicities are graded according to the CTCAE V4

    Measured: 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

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

    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

    Measured: 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)

  6. correlate molecular characteristics in patients with the efficacy endpoints (response rate, progression-free and overall survival) in each substudy

    tumor response is defined as a complete or partial response, upon RECIST v1.1 criteria

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Apr 2014 (estimated)
  2. Study start23 Apr 2014
  3. Primary completion22 Dec 2018
  4. Study completionDec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
999 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02117167
Sponsor's protocol ID
UC-0105/1305 / IFCT 1301
Other IDs
2013-001653-27
Acronym
SAFIR02_Lung
Status last verified
Jan 2024
First submitted
8 Apr 2014
Last updated
10 Jan 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 26410619

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing AZD2014, AZD4547 and AZD5363 in people with Non-small Cell Lung Cancer Metastatic, run by UNICANCER at 37 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 37 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02117167, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2024.

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