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
馃嚝馃嚪Amiens, France
Centre Antoine Lacassagne
馃嚝馃嚪Nice, France
H么pital Europ茅en Georges Pompidou
馃嚝馃嚪Paris, France
H么pital Bichat - Claude - Bernard
馃嚝馃嚪Paris, France
Hopital Tenon - Pneumologie
馃嚝馃嚪Paris, France
HIA Val-de-Gr芒ce
馃嚝馃嚪Paris, France
H么pital Saint-Joseph
馃嚝馃嚪Paris, France
Paris - Curie
馃嚝馃嚪Paris, France
Perpignan - Ch
馃嚝馃嚪Perpignan, France
CHU de Reims
馃嚝馃嚪Reims, France
Saint Quentin - CH
馃嚝馃嚪Saint Quentin, France
CHU Besancon - Pneumologie
馃嚝馃嚪Besancon, France
CH
馃嚝馃嚪Longjumeau, France
Centre Hospitalier - Pneumologie
馃嚝馃嚪Le Mans, France
Caen - CHU C么te de Nacre
馃嚝馃嚪Caen, France
Annemasse - CH
馃嚝馃嚪Ambilly, France
Angers - CHU
馃嚝馃嚪Angers, France
HCL H么pital Louis Pradel
馃嚝馃嚪Bron, France
CH de la C么te Basque
馃嚝馃嚪Bayonne, France
B茅ziers - CH
馃嚝馃嚪B茅ziers, France
Bobigny - H么pital Avicenne
馃嚝馃嚪Bobigny, France
H么pital Ambroise Par茅 - Pneumologie
馃嚝馃嚪Boulogne, France
Caen - Centre Fran莽ois Baclesse
馃嚝馃嚪Caen, France
Centre Hospitalier
馃嚝馃嚪Rambouillet, France
Cahors - CH
馃嚝馃嚪Cahors, France
Chamb茅ry - CH
馃嚝馃嚪Chamb茅ry, France
H么pital de Cholet - Pneumologie
馃嚝馃嚪Cholet, France
Clamart - H么pital Percy
馃嚝馃嚪Clamart, France
Grenoble - CHU
馃嚝馃嚪Grenoble, France
Clinique des C猫dres
馃嚝馃嚪Cornebarrieu, France
Cr茅teil - CHI
馃嚝馃嚪Cr茅teil, France
CHU
馃嚝馃嚪Clermont-Ferrand, France
CH de Dax
馃嚝馃嚪Dax, France
Dijon - CAC
馃嚝馃嚪Dijon, France
Chartres - CH
馃嚝馃嚪Le Coudray, France
CHU (H么pital Calmette) - Pneumologie
馃嚝馃嚪Lille, France
H么pital Nord - Oncologie Multidisciplinaire & Innovations Th茅rapeutiques
馃嚝馃嚪Marseille, France
Institut Paoli Calmette
馃嚝馃嚪Marseille, France
Polyclinique du Val de Sambre
馃嚝馃嚪Maubeuge, France
Mulhouse - CH
馃嚝馃嚪Mulhouse, France
Mont de Marsan - CH
馃嚝馃嚪Mont de Marsan, France
CHU Nancy
馃嚝馃嚪Nancy, France
Nantes - Centre Ren茅 Gauducheau
馃嚝馃嚪Nantes, France
Nevers - CH
馃嚝馃嚪Nevers, France
Pau - CH
馃嚝馃嚪Pau, France
Institut Jean Godinot
馃嚝馃嚪Reims, France
Rouen - CHU
馃嚝馃嚪Rouen, France
HCL - Lyon Sud (Pneumologie)
馃嚝馃嚪Pierre B茅nite, France
Strasbourg - NHC
馃嚝馃嚪Strasbourg, France
Suresnes - Hopital Foch
馃嚝馃嚪Suresnes, France
Toulouse - CHU Larrey
馃嚝馃嚪Toulouse, France
Centre Hospitalier Intercommunal
馃嚝馃嚪Toulon, France
Clinique Pasteur
馃嚝馃嚪Toulouse, France
CH de Villefranche - Pneumologie
馃嚝馃嚪Villefranche, France
Tourcoing - CH
馃嚝馃嚪Tourcoing, France
Institut Gustave Roussy
馃嚝馃嚪Villejuif, France
Versailles - CH
馃嚝馃嚪Versailles, France
CHI de la Haute-Sa么ne - Pneumologie
馃嚝馃嚪Vesoul, France
CHU Tours - Pneumologie
馃嚝馃嚪Tours, France