Clinical trial NCT01556191: Lung Cancer in Women Treated With Anti-oestrogens anD Inhibitors of EGFR
Official title: Phase II Randomised Clinical Trial Evaluating an EGFR Tyrosine Kinase Inhibitor (EGFR-TKI) Versus an EGFR-TKI Combined With an Anti-oestrogen Treatment (Fulvestrant) in Women With Advanced Stage Non-squamous Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Stage IV Lung Cancer
Keywords: lung cancer
women
Lead sponsor: Intergroupe Francophone de Cancerologie Thoracique
Sponsor class: OTHER
First posted: 2012-03-16
Enrollment: 379
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Lung Cancer is to become the first cause of death related to cancer in France as it's already the case in United States. At Present, Lung Cancer in women and in men is treated similarly. Nevertheless, numerous studies shows that lung cancer in women has specificities : at the time of the diagnosis female patients are younger, there are less clinical signs, clinical stages are earlier, histology is often adenocarcinoma. The link with tabagism is weaker . Sensitivity to tabagism is higher (more cancer in women with the same tabagism). Response rate to chemotherapy is better. Prognosis is better

Numerous hypotheses have been put forward to account for the specific characteristics of female lung cancer described above.

* One hypothesis is that there are different genetic anomalies in women. Some studies show an increase of EGFR mutation and HER2 expression and a decrease of expression of repair enzymes (ERCC1, RRM1, BRCA) which can explain the increase sensitivity to tabagism and to chemotherapy.
* Another hypothesis is that hormones play a role in oncogenesis. Indeed, lung cancer presents hormonal risk factors : pre-menopause, less than 3 kids, short menstrual cycle, hormone replacement therapy. Estrogens would have a deleterious effect on cancer incidence and on survival of lung cancer in women. Cellular and animal models show that ER pathway is activated in lung cancer and participates in oncogenesis.
* Moreover an interaction between RE and EGFR pathway has been demonstrated on lung cancer cell lines and mouse models.

EGFR-TKI have shown benefit in women with wild type EGFR or unknown status (with erlotinib) and in women with EGFR mutations (with gefitinib). In this study, the use of these two treatment will be in accordance with their market authorisations.

The objective of this study is to test the addition of an anti-estrogen (fulvestrant) to EGFR-TKI. Fulvestrant is a pure anti-oestrogen that binds to ER, blocks it and accelerates its breakdown. It has a market authorisation in breast cancer. Furthermore the association between EGFR-TKI and anti-estrogen could have a synergetic effect due to interaction between RE and EGFR pathways .


Eligibility criteria: Inclusion Criteria:

* Histologically confirmed predominant non-squamous, non-small cell lung cancer
* The presence of analysable tissue for the research of EGFR activating mutation. Analysis must be performed in INCa-labelled laboratories or platforms according to a validated technique
* Not suitable for radiation, inoperable stage III or stage IV
* Patients with an EGFR mutation must never have taken chemotherapy or must be in progression after only one previous line of chemotherapy (including maintenance). Patients without an EGFR mutation must have received one or two lines of chemotherapy beforehand. Maintenance chemotherapy is not considered to be a treatment line. Adjuvant chemotherapy is not considered to be a first line of treatment if it dates back to over a year
* Female
* Menopausal: older than 60 years of age or history of ovariectomy or younger than 60 years old with amenorrhoea for more than 12 months or an FSH rate that corresponds to a post-menopausal rate (according to the laboratory)

Exclusion Criteria:

* History of cancer except for skin cancer or cancer dating from over five years ago and considered to be cured
* Known or suspected Cerebral metastases or spinal cord compression unless they are asymptomatic without treatment or stable after being treated by surgery and/or radiation therapy. Corticosteroid treatments for symptoms must have discontinued for more than four weeks
* Pregnancy and breast-feeding
* Patient taking hormone replacement therapy for menopause that has not been stopped two weeks before the start of the trial treatment
* A change in bone marrow, kidney and liver functions inconsistent with treatment

Primary outcomes:
measure: progression-free survival
timeFrame: Around nine months
measure: Progression free survival
timeFrame: Around three months
Secondary outcomes:
measure: toxicity of EGFR-TKI and fulvestrant
timeFrame: Around three months
measure: Response rate
timeFrame: Around three months
measure: Overall survival
timeFrame: Up to 18 months
measure: toxicity of EGFR-TKI and fulvestrant
timeFrame: Around Nine months
measure: Response rate
timeFrame: Around nine months
Other outcomes:
Locations:
city: Ambilly
country: France
facility: Annemasse - CH
city: Amiens
country: France
facility: Clinique de l'Europe
city: Angers
country: France
facility: Angers - CHU
city: Bayonne
country: France
facility: CH de la Côte Basque
city: Besancon
country: France
facility: CHU Besancon - Pneumologie
city: Bobigny
country: France
facility: Bobigny - Hôpital Avicenne
city: Boulogne
country: France
facility: Hôpital Ambroise Paré - Pneumologie
city: Bron
country: France
facility: HCL Hôpital Louis Pradel
city: Béziers
country: France
facility: Béziers - CH
city: Caen
country: France
facility: Caen - Centre François Baclesse
city: Caen
country: France
facility: Caen - CHU Côte de Nacre
city: Cahors
country: France
facility: Cahors - CH
city: Chambéry
country: France
facility: Chambéry - CH
city: Chauny
country: France
facility: Centre Hospitalier
city: Cholet
country: France
facility: Hôpital de Cholet - Pneumologie
city: Clamart
country: France
facility: Clamart - Hôpital Percy
city: Clermont-Ferrand
country: France
facility: CHU
city: Colmar
country: France
facility: CH
city: Cornebarrieu
country: France
facility: Clinique des Cèdres
city: Créteil
country: France
facility: Créteil - CHI
city: Dax
country: France
facility: CH de Dax
city: Dijon
country: France
facility: Dijon - CAC
city: Grenoble
country: France
facility: Grenoble - CHU
city: Le Coudray
country: France
facility: Chartres - CH
city: Le Mans
country: France
facility: Centre Hospitalier - Pneumologie
city: Lille
country: France
facility: CHU (Hôpital Calmette) - Pneumologie
city: Longjumeau
country: France
facility: CH
city: Marseille
country: France
facility: Hôpital Nord - Oncologie Multidisciplinaire & Innovations Thérapeutiques
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Maubeuge
country: France
facility: Polyclinique du Val de Sambre
city: Mont de Marsan
country: France
facility: Mont de Marsan - CH
city: Mulhouse
country: France
facility: Mulhouse - CH
city: Nancy
country: France
facility: CHU Nancy
city: Nantes
country: France
facility: Nantes - Centre René Gauducheau
city: Nevers
country: France
facility: Nevers - CH
city: Nice
country: France
facility: Centre Antoine Lacassagne
city: Paris
country: France
facility: Hopital Tenon - Pneumologie
city: Paris
country: France
facility: HIA Val-de-Grâce
city: Paris
country: France
facility: Hôpital Bichat - Claude - Bernard
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Paris
country: France
facility: Hôpital Saint-Joseph
city: Paris
country: France
facility: Paris - Curie
city: Pau
country: France
facility: Pau - CH
city: Perpignan
country: France
facility: Perpignan - Ch
city: Pierre Bénite
country: France
facility: HCL - Lyon Sud (Pneumologie)
city: Rambouillet
country: France
facility: Centre Hospitalier
city: Reims
country: France
facility: CHU de Reims
city: Reims
country: France
facility: Institut Jean Godinot
city: Rouen
country: France
facility: Rouen - CHU
city: Saint Quentin
country: France
facility: Saint Quentin - CH
city: Strasbourg
country: France
facility: Strasbourg - NHC
city: Suresnes
country: France
facility: Suresnes - Hopital Foch
city: Toulon
country: France
facility: Centre Hospitalier Intercommunal
city: Toulouse
country: France
facility: Clinique Pasteur
city: Toulouse
country: France
facility: Toulouse - CHU Larrey
city: Tourcoing
country: France
facility: Tourcoing - CH
city: Tours
country: France
facility: CHU Tours - Pneumologie
city: Versailles
country: France
facility: Versailles - CH
city: Vesoul
country: France
facility: CHI de la Haute-Saône - Pneumologie
city: Villefranche
country: France
facility: CH de Villefranche - Pneumologie
city: Villejuif
country: France
facility: Institut Gustave Roussy
Study officials:
affiliation: University Hospital, Toulouse
name: Julien MAZIERES, MD, phD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mazieres J, Barlesi F, Rouquette I, Molinier O, Besse B, Monnet I, Audigier-Valette C, Toffart AC, Renault PA, Fraboulet S, Hiret S, Mennecier B, Debieuvre D, Westeel V, Masson P, Madroszyk-Flandin A, Pichon E, Cortot AB, Amour E, Morin F, Zalcman G, Moro-Sibilot D, Souquet PJ. Randomized Phase II Trial Evaluating Treatment with EGFR-TKI Associated with Antiestrogen in Women with Nonsquamous Advanced-Stage NSCLC: IFCT-1003 LADIE Trial. Clin Cancer Res. 2020 Jul 1;26(13):3172-3181. doi: 10.1158/1078-0432.CCR-19-3056. Epub 2020 Mar 6.