Lung Cancer in Women Treated With Anti-oestrogens anD Inhibitors of EGFR
LADIE
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
1 other identifier
interventional
379
1 country
61
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 .
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started May 2012
Longer than P75 for phase_2
61 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 8, 2012
CompletedFirst Posted
Study publicly available on registry
March 16, 2012
CompletedStudy Start
First participant enrolled
May 15, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 15, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 17, 2020
CompletedJanuary 8, 2021
January 1, 2021
6 years
March 8, 2012
January 6, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
progression-free survival
From date of randomization until the date of first progression for EGFR mutated patient
Around nine months
Progression free survival
From date of randomization until the date of first progression for EGFR wild type patients
Around three months
Secondary Outcomes (5)
toxicity of EGFR-TKI and fulvestrant
Around three months
Response rate
Around three months
Overall survival
Up to 18 months
toxicity of EGFR-TKI and fulvestrant
Around Nine months
Response rate
Around nine months
Study Arms (4)
Gefinitib + Fulvestrant (patient with EGFR mutations)
EXPERIMENTALErlotinib (wild type patients)
ACTIVE COMPARATORErlotinib + Fulvestrant (wild type patients)
EXPERIMENTALGefinib (patient with EGFR mutations)
ACTIVE COMPARATORInterventions
250 mg per day (oral)
500 mg (2 x 250 mg), IV by month with an additional 500 mg dose two weeks after the initial dose
150 mg per day (oral)
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (61)
Annemasse - CH
Ambilly, 74100, France
Clinique de l'Europe
Amiens, France
Angers - CHU
Angers, 49000, France
CH de la Côte Basque
Bayonne, France
CHU Besancon - Pneumologie
Besançon, 25000, France
Béziers - CH
Béziers, 34525, France
Bobigny - Hôpital Avicenne
Bobigny, 93000, France
Hôpital Ambroise Paré - Pneumologie
Boulogne, France
HCL Hôpital Louis Pradel
Bron, France
Caen - Centre François Baclesse
Caen, 14000, France
Caen - CHU Côte de Nacre
Caen, 14000, France
Cahors - CH
Cahors, 46000, France
Chambéry - CH
Chambéry, France
Centre Hospitalier
Chauny, France
Hôpital de Cholet - Pneumologie
Cholet, France
Clamart - Hôpital Percy
Clamart, 92140, France
CHU
Clermont-Ferrand, France
CH
Colmar, France
Clinique des Cèdres
Cornebarrieu, France
Créteil - CHI
Créteil, 94000, France
CH de Dax
Dax, France
Dijon - CAC
Dijon, 21000, France
Grenoble - CHU
Grenoble, 38000, France
Chartres - CH
Le Coudray, 28630, France
Centre Hospitalier - Pneumologie
Le Mans, 72000, France
CHU (Hôpital Calmette) - Pneumologie
Lille, 59000, 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, 40000, France
Mulhouse - CH
Mulhouse, 68000, France
CHU Nancy
Nancy, France
Nantes - Centre René Gauducheau
Nantes, 44805, France
Nevers - CH
Nevers, 58033, France
Centre Antoine Lacassagne
Nice, France
Hopital Tenon - Pneumologie
Paris, 75020, France
HIA Val-de-Grâce
Paris, France
Hôpital Bichat - Claude - Bernard
Paris, France
Hôpital Européen Georges Pompidou
Paris, France
Hôpital Saint-Joseph
Paris, France
Paris - Curie
Paris, France
Pau - CH
Pau, 64046, France
Perpignan - Ch
Perpignan, 66046, France
HCL - Lyon Sud (Pneumologie)
Pierre-Bénite, 69495, France
Centre Hospitalier
Rambouillet, France
CHU de Reims
Reims, France
Institut Jean Godinot
Reims, France
Rouen - CHU
Rouen, 76000, France
Saint Quentin - CH
Saint-Quentin, 02100, France
Strasbourg - NHC
Strasbourg, 63000, France
Suresnes - Hopital Foch
Suresnes, 92151, France
Centre Hospitalier Intercommunal
Toulon, France
Clinique Pasteur
Toulouse, France
Toulouse - CHU Larrey
Toulouse, France
Tourcoing - CH
Tourcoing, 59208, France
CHU Tours - Pneumologie
Tours, France
Versailles - CH
Versailles, 78157, France
CHI de la Haute-Saône - Pneumologie
Vesoul, France
CH de Villefranche - Pneumologie
Villefranche, France
Institut Gustave Roussy
Villejuif, 94800, France
Related Publications (1)
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.
PMID: 32144133DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Julien MAZIERES, MD, phD
University Hospital, Toulouse
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 8, 2012
First Posted
March 16, 2012
Study Start
May 15, 2012
Primary Completion
May 15, 2018
Study Completion
June 17, 2020
Last Updated
January 8, 2021
Record last verified: 2021-01