Clinical trial NCT02178397: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: NSCLC Patients With EGFR Activating Mutation
Keywords: erlotinib
lung cancer
EGFR mutation
Lead sponsor: Centre Francois Baclesse
Sponsor class: OTHER
Collaborators: name: Groupe Francais De Pneumo-Cancerologie
name: Hoffmann-La Roche
First posted: 2014-06-30
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Efficacy by PFS
timeFrame: From date of randomization until the date of first documented progression evaluated every 6-9 weeks
Secondary outcomes:
measure: scores of QoL
timeFrame: at 4 months after inclusion
measure: Overall survival
timeFrame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 100 months
measure: Tumoral response
timeFrame: every 6-9 weeks
measure: Toxicities
timeFrame: From date of randomization until study participation, assessed up to 100 months
measure: Rebound phenomenon (flare)
timeFrame: within 3 weeks after disease progression before inclusion
Other outcomes:
Locations:
city: Aix En Provence
country: France
facility: CH
city: Amiens
country: France
facility: CH
city: Angers
country: France
facility: CHRU
city: Annecy
country: France
facility: CH
city: Brest
country: France
facility: CHU
city: Caen
country: France
facility: Centre François BACLESSE
city: Creteil
country: France
facility: CHIC
city: Draguignan
country: France
facility: CH
city: Elbeuf
country: France
facility: CH
city: GAP
country: France
facility: CHIC
city: La Roche/yon
country: France
facility: Ch La Roche/Yon
city: Le MANS
country: France
facility: Centre Hospitalier
city: Lille
country: France
facility: Centre Oscar Lambret
city: Limoges
country: France
facility: CHU
city: Longjumeau
country: France
facility: CH
city: Lorient
country: France
facility: CH
city: Macon
country: France
facility: CH
city: Mantes La Jolie
country: France
facility: CH
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Marseille
country: France
facility: AP-HM - Hôpital Nord
city: Meaux
country: France
facility: CH
city: Meulan
country: France
facility: Centre Hospitalier Intercommunal
city: PAU
country: France
facility: CH
city: Perpignan
country: France
facility: Centre Catalan
city: Rennes
country: France
facility: CHU
city: Roanne
country: France
facility: CH
city: Rouen
country: France
facility: CHU
city: Salon de Provence
country: France
facility: CH
city: Sens
country: France
facility: CH
city: St BRIEUC
country: France
facility: CH
city: St ETIENNE
country: France
facility: Institut de Cancérologie de la Loire
city: Strasbourg
country: France
facility: Centre Paul Strauss
city: Tarbes
country: France
facility: CH
city: Toulon
country: France
facility: Hôpital d'instruction des Armées Sainte-Anne
city: Villefranche
country: France
facility: CH
Study officials:
affiliation: Centre François Baclesse - CAEN- FRANCE
name: Radj GERVAIS, MD
role: PRINCIPAL_INVESTIGATOR
References: