Lung Cancer in Women Treated With Anti-oestrogens anD Inhibitors of EGFR
- Conditions
- Stage IV Lung Cancer
- Interventions
- Registration Number
- NCT01556191
- Lead Sponsor
- Intergroupe Francophone de Cancerologie Thoracique
- 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 .
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 379
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Gefinitib + Fulvestrant (patient with EGFR mutations) Gefitinib - Gefinitib + Fulvestrant (patient with EGFR mutations) Fulvestrant - Erlotinib + Fulvestrant (wild type patients) Erlotinib - Erlotinib (wild type patients) Erlotinib - Erlotinib + Fulvestrant (wild type patients) Fulvestrant - Gefinib (patient with EGFR mutations) Gefitinib -
- Primary Outcome Measures
Name Time Method progression-free survival Around nine months From date of randomization until the date of first progression for EGFR mutated patient
Progression free survival Around three months From date of randomization until the date of first progression for EGFR wild type patients
- Secondary Outcome Measures
Name Time Method Response rate Around nine months For EGFR-Mutated patients
Overall survival Up to 18 months For all patients
toxicity of EGFR-TKI and fulvestrant Around Nine months The number of patients for whom at least an adverse event will have been reported, the number of events, according to the relation to the treatment, the intensity, and the cycle of appearance for EGFR mutated patients
Trial Locations
- Locations (59)
Clinique de l'Europe
🇫🇷Amiens, France
Centre Antoine Lacassagne
🇫🇷Nice, France
Hôpital Européen Georges Pompidou
🇫🇷Paris, France
Hôpital Bichat - Claude - Bernard
🇫🇷Paris, France
Hopital Tenon - Pneumologie
🇫🇷Paris, France
HIA Val-de-Grâce
🇫🇷Paris, France
Hôpital Saint-Joseph
🇫🇷Paris, France
Paris - Curie
🇫🇷Paris, France
Perpignan - Ch
🇫🇷Perpignan, France
CHU de Reims
🇫🇷Reims, France
Saint Quentin - CH
🇫🇷Saint Quentin, France
CHU Besancon - Pneumologie
🇫🇷Besancon, France
CH
🇫🇷Longjumeau, France
Centre Hospitalier - Pneumologie
🇫🇷Le Mans, France
Caen - CHU Côte de Nacre
🇫🇷Caen, France
Annemasse - CH
🇫🇷Ambilly, France
Angers - CHU
🇫🇷Angers, France
HCL Hôpital Louis Pradel
🇫🇷Bron, France
CH de la Côte Basque
🇫🇷Bayonne, France
Béziers - CH
🇫🇷Béziers, France
Bobigny - Hôpital Avicenne
🇫🇷Bobigny, France
Hôpital Ambroise Paré - Pneumologie
🇫🇷Boulogne, France
Caen - Centre François Baclesse
🇫🇷Caen, France
Centre Hospitalier
🇫🇷Rambouillet, France
Cahors - CH
🇫🇷Cahors, France
Chambéry - CH
🇫🇷Chambéry, France
Hôpital de Cholet - Pneumologie
🇫🇷Cholet, France
Clamart - Hôpital Percy
🇫🇷Clamart, France
Grenoble - CHU
🇫🇷Grenoble, France
Clinique des Cèdres
🇫🇷Cornebarrieu, France
Créteil - CHI
🇫🇷Créteil, France
CHU
🇫🇷Clermont-Ferrand, France
CH de Dax
🇫🇷Dax, France
Dijon - CAC
🇫🇷Dijon, France
Chartres - CH
🇫🇷Le Coudray, France
CHU (Hôpital Calmette) - Pneumologie
🇫🇷Lille, France
Hôpital Nord - Oncologie Multidisciplinaire & Innovations Thérapeutiques
🇫🇷Marseille, France
Institut Paoli Calmette
🇫🇷Marseille, France
Polyclinique du Val de Sambre
🇫🇷Maubeuge, France
Mulhouse - CH
🇫🇷Mulhouse, France
Mont de Marsan - CH
🇫🇷Mont de Marsan, France
CHU Nancy
🇫🇷Nancy, France
Nantes - Centre René Gauducheau
🇫🇷Nantes, France
Nevers - CH
🇫🇷Nevers, France
Pau - CH
🇫🇷Pau, France
Institut Jean Godinot
🇫🇷Reims, France
Rouen - CHU
🇫🇷Rouen, France
HCL - Lyon Sud (Pneumologie)
🇫🇷Pierre Bénite, France
Strasbourg - NHC
🇫🇷Strasbourg, France
Suresnes - Hopital Foch
🇫🇷Suresnes, France
Toulouse - CHU Larrey
🇫🇷Toulouse, France
Centre Hospitalier Intercommunal
🇫🇷Toulon, France
Clinique Pasteur
🇫🇷Toulouse, France
CH de Villefranche - Pneumologie
🇫🇷Villefranche, France
Tourcoing - CH
🇫🇷Tourcoing, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Versailles - CH
🇫🇷Versailles, France
CHI de la Haute-Saône - Pneumologie
🇫🇷Vesoul, France
CHU Tours - Pneumologie
🇫🇷Tours, France