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

NCT02178397 | Terminated Phase 3 DMC

• 1 other identifier: FLARE /GFPC 03-2013
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 35

Brief Summary

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.

Conditions

NSCLC Patients With EGFR Activating Mutation

Keywords

erlotinib; lung cancer; EGFR mutation

Outcome Measures

Primary Outcomes (1)

• Efficacy by PFS

  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

Secondary Outcomes (5)

• scores of QoL

  at 4 months after inclusion

• Overall survival

  From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months

• Tumoral response

  every 6-9 weeks

• Toxicities

  From date of randomization until study participation, assessed up to 100 months

• Rebound phenomenon (flare)

  within 3 weeks after disease progression before inclusion

Study Arms (2)

EXPERIMENTAL ARM B

EXPERIMENTAL

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

Drug: ERLOTINIB WITH CHEMOTHERAPY

STANDARD ARM A

ACTIVE COMPARATOR

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

Drug: CHEMOTHERAPY ONLY

Interventions

ERLOTINIB WITH CHEMOTHERAPY DRUG

EXPERIMENTAL ARM B

CHEMOTHERAPY ONLY DRUG

STANDARD ARM A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Centre Francois Baclesse: lead
• Groupe Francais De Pneumo-Cancerologie: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (35)

CH

Aix-en-Provence, France

Location

CH

Amiens, France

Location

CHRU

Angers, 49933, France

Location

CH

Annecy, 74374, France

Location

CHU

Brest, 29609, France

Location

Centre François BACLESSE

Caen, 14000, France

Location

CHIC

Créteil, 94000, France

Location

CH

Draguignan, 83007, France

Location

CH

Elbeuf, France

Location

CHIC

Gap, 05007, France

Location

Ch La Roche/Yon

La Roche/yon, France

Location

Centre Hospitalier

Le Mans, 72037, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

CHU

Limoges, 87042, France

Location

CH

Longjumeau, 91160, France

Location

CH

Lorient, 35632, France

Location

CH

Mantes-la-Jolie, 78201, France

Location

Institut Paoli Calmettes

Marseille, 13273, France

Location

AP-HM - Hôpital Nord

Marseille, France

Location

CH

Mâcon, 71018, France

Location

CH

Meaux, 77104, France

Location

Centre Hospitalier Intercommunal

Meulan-en-Yvelines, 78250, France

Location

CH

Pau, France

Location

Centre Catalan

Perpignan, France

Location

CHU

Rennes, 35033, France

Location

CH

Roanne, France

Location

CHU

Rouen, France

Location

CH

Saint-Brieuc, France

Location

Institut de Cancérologie de la Loire

Saint-Etienne, 42271, France

Location

CH

Salon-de-Provence, France

Location

CH

Sens, 89100, France

Location

Centre Paul Strauss

Strasbourg, 67065, France

Location

CH

Tarbes, France

Location

Hôpital d'instruction des Armées Sainte-Anne

Toulon, 83041, France

Location

CH

Villefranche, 69655, France

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Erlotinib Hydrochloride; Drug Therapy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Therapeutics

Study Officials

• Radj GERVAIS, MD

  Centre François Baclesse - CAEN- FRANCE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2014
• First Posted: June 30, 2014
• Study Start: June 1, 2014
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: July 17, 2017

Record last verified: 2016-07

Locations

FR (35)