Lung Cancer in Women Treated With Anti-oestrogens anD Inhibitors of EGFR

Stage IV Lung Cancer Clinical Trial

— LADIE  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01556191
• Other study ID #: IFCT-1003
• Status: Completed
• Phase: Phase 2
• Start date: May 15, 2012
• Est. completion date: June 17, 2020

Study information

• Verified date: January 2021
• Source: Intergroupe Francophone de Cancerologie Thoracique
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 .

Recruitment information / eligibility

• Status: Completed
• Enrollment: 379
• Est. completion date: June 17, 2020
• Est. primary completion date: May 15, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Lung Neoplasms
• Stage IV Lung Cancer

Intervention

Drug:
• Gefitinib
250 mg per day (oral)
• Fulvestrant
500 mg (2 x 250 mg), IV by month with an additional 500 mg dose two weeks after the initial dose
• Erlotinib
150 mg per day (oral)

Locations

Country	Name	City	State
France	Annemasse - CH	Ambilly
France	Clinique de l'Europe	Amiens
France	Angers - CHU	Angers
France	CH de la Côte Basque	Bayonne
France	CHU Besancon - Pneumologie	Besancon
France	Béziers - CH	Béziers
France	Bobigny - Hôpital Avicenne	Bobigny
France	Hôpital Ambroise Paré - Pneumologie	Boulogne
France	HCL Hôpital Louis Pradel	Bron
France	Caen - Centre François Baclesse	Caen
France	Caen - CHU Côte de Nacre	Caen
France	Cahors - CH	Cahors
France	Chambéry - CH	Chambéry
France	Centre Hospitalier	Chauny
France	Hôpital de Cholet - Pneumologie	Cholet
France	Clamart - Hôpital Percy	Clamart
France	CHU	Clermont-Ferrand
France	CH	Colmar
France	Clinique des Cèdres	Cornebarrieu
France	Créteil - CHI	Créteil
France	CH de Dax	Dax
France	Dijon - CAC	Dijon
France	Grenoble - CHU	Grenoble
France	Chartres - CH	Le Coudray
France	Centre Hospitalier - Pneumologie	Le Mans
France	CHU (Hôpital Calmette) - Pneumologie	Lille
France	CH	Longjumeau
France	Hôpital Nord - Oncologie Multidisciplinaire & Innovations Thérapeutiques	Marseille
France	Institut Paoli Calmette	Marseille
France	Polyclinique du Val de Sambre	Maubeuge
France	Mont de Marsan - CH	Mont de Marsan
France	Mulhouse - CH	Mulhouse
France	CHU Nancy	Nancy
France	Nantes - Centre René Gauducheau	Nantes
France	Nevers - CH	Nevers
France	Centre Antoine Lacassagne	Nice
France	HIA Val-de-Grâce	Paris
France	Hôpital Bichat - Claude - Bernard	Paris
France	Hôpital Européen Georges Pompidou	Paris
France	Hôpital Saint-Joseph	Paris
France	Hopital Tenon - Pneumologie	Paris
France	Paris - Curie	Paris
France	Pau - CH	Pau
France	Perpignan - Ch	Perpignan
France	HCL - Lyon Sud (Pneumologie)	Pierre Bénite
France	Centre Hospitalier	Rambouillet
France	CHU de Reims	Reims
France	Institut Jean Godinot	Reims
France	Rouen - CHU	Rouen
France	Saint Quentin - CH	Saint Quentin
France	Strasbourg - NHC	Strasbourg
France	Suresnes - Hopital Foch	Suresnes
France	Centre Hospitalier Intercommunal	Toulon
France	Clinique Pasteur	Toulouse
France	Toulouse - CHU Larrey	Toulouse
France	Tourcoing - CH	Tourcoing
France	CHU Tours - Pneumologie	Tours
France	Versailles - CH	Versailles
France	CHI de la Haute-Saône - Pneumologie	Vesoul
France	CH de Villefranche - Pneumologie	Villefranche
France	Institut Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Intergroupe Francophone de Cancerologie Thoracique

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	progression-free survival	From date of randomization until the date of first progression for EGFR mutated patient	Around nine months
Primary	Progression free survival	From date of randomization until the date of first progression for EGFR wild type patients	Around three months
Secondary	toxicity of EGFR-TKI and fulvestrant	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 WT patients	Around three months
Secondary	Response rate	For EGFR WT patients	Around three months
Secondary	Overall survival	For all patients	Up to 18 months
Secondary	toxicity of EGFR-TKI and fulvestrant	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	Around Nine months
Secondary	Response rate	For EGFR-Mutated patients	Around nine months

External Links

•   IFCT official website