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A Multicenter Randomized Phase III Study Comparing Second-line Treatment With Chemotherapy Associated or Not to Erlotinib in NSCLC Patients With Secondary Resistance to TKI-EGFR (FLARE)

13 luglio 2017 aggiornato da: Centre Francois Baclesse

The current first line treatment of patients with EGFR activating mutation lung cancer is EGFR TKI. Compared to platinum-based chemotherapy, EGFR-TKIs are superior in terms of response rate and progression-free survival. However, an acquired resistance occurs almost constantly. The second-line treatment includes platinum-based chemotherapy in the absence of contraindication. This chemotherapy is then administered after discontinuing EGFR TKIs.

However, a rebound phenomenon of the disease was described in patients who discontinued EGFR TKIs. Some clinical teams therefore recommend, as a precaution, in order to avoid any withdrawal phenomenon, to never discontinue EGFR TKIs in patients developing an EGFR TKI acquired resistance.

It seems therefore useful to conduct a study to better define the therapeutic strategy to adopt in patients developing an acquired resistance after having received EGFR TKIs as first line treatment.

Panoramica dello studio

Stato

Terminato

Condizioni

Intervento / Trattamento

Tipo di studio

Interventistico

Iscrizione (Effettivo)

6

Fase

  • Fase 3

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Francia
      • Aix En Provence, Francia
        • CH
      • Amiens, Francia
        • CH
      • Angers, Francia, 49933
        • CHRU
      • Annecy, Francia, 74374
        • CH
      • Brest, Francia, 29609
        • CHU
      • Caen, Francia, 14000
        • Centre Francois Baclesse
      • Creteil, Francia, 94000
        • CHIC
      • Draguignan, Francia, 83007
        • CH
      • Elbeuf, Francia
        • CH
      • GAP, Francia, 05007
        • CHIC
      • La Roche/yon, Francia
        • Ch La Roche/Yon
      • Le MANS, Francia, 72037
        • Centre hospitalier
      • Lille, Francia, 59020
        • Centre Oscar Lambret
      • Limoges, Francia, 87042
        • CHU
      • Longjumeau, Francia, 91160
        • CH
      • Lorient, Francia, 35632
        • CH
      • Macon, Francia, 71018
        • CH
      • Mantes La Jolie, Francia, 78201
        • CH
      • Marseille, Francia, 13273
        • Institut Paoli Calmettes
      • Marseille, Francia
        • AP-HM - Hôpital Nord
      • Meaux, Francia, 77104
        • CH
      • Meulan, Francia, 78250
        • Centre Hospitalier Intercommunal
      • PAU, Francia
        • CH
      • Perpignan, Francia
        • Centre Catalan
      • Rennes, Francia, 35033
        • CHU
      • Roanne, Francia
        • CH
      • Rouen, Francia
        • CHU
      • Salon de Provence, Francia
        • CH
      • Sens, Francia, 89100
        • CH
      • St BRIEUC, Francia
        • CH
      • St ETIENNE, Francia, 42271
        • Institut de Cancerologie de La Loire
      • Strasbourg, Francia, 67065
        • Centre Paul Strauss
      • Tarbes, Francia
        • CH
      • Toulon, Francia, 83041
        • Hôpital d'instruction des armées Sainte-Anne
      • Villefranche, Francia, 69655
        • CH

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

18 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

Inclusion Criteria:

  • Man or woman aged 18 years or more
  • Non-small cell lung cancer carcinoma (NSCLC) cytologically or histologically confirmed
  • Measurable disease according to RECIST 1.1 criteria
  • Life expectancy greater than 12 weeks
  • Performance Status (ECOG) ≤ 2
  • Stage IIIB considered ineligible for thoracic radiotherapy at "curative" doses or stage IV
  • Presence of at least one measurable target lesion
  • Documented disease progression (RECIST 1.1) after first line treatment with erlotinib, during at least 4 months in case of partial or complete response according to RECIST criteria, or 6 months in case of stable disease. The treatment with Erlotinib should not be discontinued for more than 8 days between the progression and the inclusion in the study. The daily dose of Erlotinib should be at least 50 mg.
  • Presence of one of the EGFR activating mutations in the tumor (exon 19 deletion or L858R, G719X or L861Q)
  • One additional line of previous chemotherapy is allowed if administered in adjuvant or neoadjuvant setting and received more than six months before.
  • Prior radiotherapy is allowed if the volume of irradiated marrow is <25% of the total bone marrow. The prior radiotherapy must be completed at least two weeks before study entry
  • Brain metastases are allowed if they are controlled without steroids and if their treatment is completed (radiotherapy and/or surgery). Patients with no symptomatic brain metastases may be included; even if brain metastases are progressive and even if they are the only site of progression (since the investigator considers that irradiation is not required). These metastases have not to be life-threatening (are excluded: cerebellar metastasis ≥ 2 cm, brainstem metastasis, brain metastasis > 3 cm and/or near important functional structure).
  • Normal Liver function (bilirubin ≤ULN, AST - ALT ≤2.5 x ULN, alkaline phosphatase ≤3 x ULN), or in case of liver metastases: alkaline phosphatase, AST-ALT ≤ 5 x ULN
  • Normal renal function: blood creatinine ≤ULN and / or creatinine clearance> 60 ml/min calculated with the MDRD formula
  • Normal blood function: absolute neutrophil count ≥ 1.5 x 109/l and / or platelets ≥ 100 x 109 / l, hemoglobin> 9 g/dl
  • Woman and man under efficient contraception during treatment and at least 6 months after the end of treatment by pemetrexed or platinum or gemcitabine
  • Signed written Informed consent

Exclusion Criteria:

  • Bronchoalveolar, mixed, neuroendocrine and small cell lung cancers
  • Patient with only bone metastases are not eligible
  • All progressive metastatic sites treated locally (surgery, radiotherapy)
  • Superior vena cava syndrome
  • Uncontrolled cardiac disease requiring treatment
  • Congestive heart failure, angina pectoris, significant arrhythmias or history of myocardial infarction within the previous 12 months
  • Neurological or psychiatric disorders
  • Uncontrolled infectious disease
  • Peripheral neuropathy grade≥ 2
  • Definitive contraindication for the use of steroids
  • Inductive anti-epileptic treatments (phenobarbital, phenytoïne)• Previous or concomitant other cancer, including skin cancer (except basal cell cancer of the skin), except in situ treated carcinoma of the cervix , except cancer treated with surgery alone without recurrence for 5 years
  • Pregnant or breastfeeding woman
  • Patient follow-up not achievable
  • Participation in a trial within the last 30 days
  • Patient deprived of liberty as a result of a justice or administrative decision

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Nessuno (etichetta aperta)

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Sperimentale: EXPERIMENTAL ARM B

INDUCTION chemotherapy: 4 cycles of

  • pemetrexed with cisplatin or carboplatin
  • or gemcitabine with cisplatin or carboplatin in combination with erlotinib

THEN, for responders and for patients with stable disease :MAINTENANCE chemotherapy by Pemetrexed in combination with erlotinib
Droga: ERLOTINIB WITH CHEMOTHERAPY
Comparatore attivo: STANDARD ARM A

INDUCTION chemotherapy: 4 cycles of

  • pemetrexed with cisplatin or carboplatin
  • or gemcitabine with cisplatin or carboplatin

THEN, for responders and for patients with stable disease :MAINTENANCE chemotherapy by Pemetrexed
Droga: CHEMOTHERAPY ONLY

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Efficacy by PFS
Lasso di tempo: From date of randomization until the date of first documented progression evaluated every 6-9 weeks
Efficacy will be assessed by the PFS, define as time between randomization of the patient in the study and disease progression (local, regional, distant and second cancer) or death (all causes). Alive patients free of progression will be censored at the last follow-up.
From date of randomization until the date of first documented progression evaluated every 6-9 weeks

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
scores of QoL
Lasso di tempo: at 4 months after inclusion
difference between the scores of QoL at baseline and at 4 months after inclusion for the three targeted dimensions of EORTC QLQ-C30 (global quality of life, fatigue and physical functioning). A difference or 10 points or more at 4 months after inclusion for one score between the 2 arms will be considered as clinically relevant.
at 4 months after inclusion
Overall survival
Lasso di tempo: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
Overall survival defined as time interval between randomization and death (all causes). Alive patients will be censored at the last date of news or data cut off
From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
Tumoral response
Lasso di tempo: every 6-9 weeks
Tumoral response (complete response, partial response, stable disease, progression) according to RECIST 1.1
every 6-9 weeks
Toxicities
Lasso di tempo: From date of randomization until study participation, assessed up to 100 months
Toxicities according to NCI-CTC-AE v.4
From date of randomization until study participation, assessed up to 100 months
Rebound phenomenon (flare)
Lasso di tempo: within 3 weeks after disease progression before inclusion
Rebound phenomenon (flare) defined by a hospitalization or a death within 3 weeks for disease progression after the end of TKI EGFR treatment (in the arm without EGFR TKI) and date of onset
within 3 weeks after disease progression before inclusion

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Centre Francois Baclesse

Collaboratori

Hoffmann-La Roche
Groupe Francais De Pneumo-Cancerologie

Investigatori

  • Investigatore principale: Radj GERVAIS, MD, Centre François Baclesse - CAEN- FRANCE

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 giugno 2014

Completamento primario (Effettivo)

1 settembre 2015

Completamento dello studio (Effettivo)

1 settembre 2015

Date di iscrizione allo studio

Primo inviato

25 giugno 2014

Primo inviato che soddisfa i criteri di controllo qualità

26 giugno 2014

Primo Inserito (Stima)

30 giugno 2014

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

17 luglio 2017

Ultimo aggiornamento inviato che soddisfa i criteri QC

13 luglio 2017

Ultimo verificato

1 luglio 2016

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • FLARE /GFPC 03-2013

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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