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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 de julio de 2017 actualizado por: 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.

Descripción general del estudio

Estado

Terminado

Condiciones

Intervención / Tratamiento

Tipo de estudio

Intervencionista

Inscripción (Actual)

6

Fase

  • Fase 3

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Ubicaciones de estudio

  • 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

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años y mayores (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Ninguno (etiqueta abierta)

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Experimental: 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
Comparador activo: 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

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Efficacy by PFS
Periodo de tiempo: 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

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
scores of QoL
Periodo de tiempo: 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
Periodo de tiempo: 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
Periodo de tiempo: every 6-9 weeks
Tumoral response (complete response, partial response, stable disease, progression) according to RECIST 1.1
every 6-9 weeks
Toxicities
Periodo de tiempo: 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)
Periodo de tiempo: 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

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Patrocinador

Centre Francois Baclesse

Colaboradores

Hoffmann-La Roche
Groupe Francais De Pneumo-Cancerologie

Investigadores

  • Investigador principal: Radj GERVAIS, MD, Centre François Baclesse - CAEN- FRANCE

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio

1 de junio de 2014

Finalización primaria (Actual)

1 de septiembre de 2015

Finalización del estudio (Actual)

1 de septiembre de 2015

Fechas de registro del estudio

Enviado por primera vez

25 de junio de 2014

Primero enviado que cumplió con los criterios de control de calidad

26 de junio de 2014

Publicado por primera vez (Estimar)

30 de junio de 2014

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

17 de julio de 2017

Última actualización enviada que cumplió con los criterios de control de calidad

13 de julio de 2017

Última verificación

1 de julio de 2016

Más información

Términos relacionados con este estudio

Palabras clave

Términos MeSH relevantes adicionales

Otros números de identificación del estudio

  • FLARE /GFPC 03-2013

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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