Lung Cancer in Women Treated With Anti-oestrogens anD Inhibitors of EGFR (LADIE)
|ClinicalTrials.gov Identifier: NCT01556191|
Recruitment Status : Active, not recruiting
First Posted : March 16, 2012
Last Update Posted : September 20, 2017
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 .
|Condition or disease||Intervention/treatment||Phase|
|Stage IV Lung Cancer||Drug: Gefitinib Drug: Fulvestrant Drug: Erlotinib||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||394 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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 Start Date :||May 2012|
|Estimated Primary Completion Date :||March 2018|
|Estimated Study Completion Date :||December 2018|
|Experimental: Gefinitib + Fulvestrant (patient with EGFR mutations)||
250 mg per day (oral)Drug: Fulvestrant
500 mg (2 x 250 mg), IV by month with an additional 500 mg dose two weeks after the initial dose
|Active Comparator: Erlotinib (wild type patients)||
150 mg per day (oral)
|Experimental: Erlotinib + Fulvestrant (wild type patients)||
500 mg (2 x 250 mg), IV by month with an additional 500 mg dose two weeks after the initial doseDrug: Erlotinib
150 mg per day (oral)
|Active Comparator: Gefinib (patient with EGFR mutations)||
250 mg per day (oral)
- progression-free survival [ Time Frame: Around nine months ]From date of randomization until the date of first progression for EGFR mutated patient
- Progression free survival [ Time Frame: Around three months ]From date of randomization until the date of first progression for EGFR wild type patients
- toxicity of EGFR-TKI and fulvestrant [ Time Frame: Around three 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 WT patients
- Response rate [ Time Frame: Around three months ]For EGFR WT patients
- Overall survival [ Time Frame: Up to 18 months ]
- Quality of life [ Time Frame: Around three months ]For EGFR WT patients
- toxicity of EGFR-TKI and fulvestrant [ Time Frame: 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
- Response rate [ Time Frame: Around nine months ]For EGFR-Mutated patients
- Quality of life [ Time Frame: Around nine months ]For EGFR mutated patients
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01556191
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|Principal Investigator:||Julien MAZIERES, MD, phD||University Hospital, Toulouse|