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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Intergroupe Francophone de Cancerologie Thoracique
Sponsor:
Information provided by (Responsible Party):
Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier:
NCT01556191
First received: March 8, 2012
Last updated: November 29, 2013
Last verified: July 2013
  Purpose

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 Intervention Phase
Stage IV Lung Cancer
Drug: Gefitinib
Drug: Fulvestrant
Drug: Erlotinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Intergroupe Francophone de Cancerologie Thoracique:

Primary Outcome Measures:
  • progression-free survival [ Time Frame: Around nine months ] [ Designated as safety issue: No ]
    From date of randomization until the date of first progression for EGFR mutated patient

  • Progression free survival [ Time Frame: Around three months ] [ Designated as safety issue: No ]
    From date of randomization until the date of first progression for EGFR wild type patients


Secondary Outcome Measures:
  • toxicity of EGFR-TKI and fulvestrant [ Time Frame: Around three months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    For EGFR WT patients

  • Overall survival [ Time Frame: Up to 18 months ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: Around three months ] [ Designated as safety issue: No ]
    For EGFR WT patients

  • toxicity of EGFR-TKI and fulvestrant [ Time Frame: Around Nine months ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    For EGFR-Mutated patients

  • Quality of life [ Time Frame: Around nine months ] [ Designated as safety issue: No ]
    For EGFR mutated patients


Estimated Enrollment: 358
Study Start Date: May 2012
Estimated Study Completion Date: May 2016
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gefinitib + Fulvestrant (patient with EGFR mutations) Drug: Gefitinib
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) Drug: Erlotinib
150 mg per day (oral)
Experimental: Erlotinib + Fulvestrant (wild type patients) Drug: Fulvestrant
500 mg (2 x 250 mg), IV by month with an additional 500 mg dose two weeks after the initial dose
Drug: Erlotinib
150 mg per day (oral)
Active Comparator: Gefinib (patient with EGFR mutations) Drug: Gefitinib
250 mg per day (oral)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556191

Contacts
Contact: Franck MORIN contact@ifct.fr
Contact: Elodie AMOUR contact@ifct.fr

  Show 62 Study Locations
Sponsors and Collaborators
Intergroupe Francophone de Cancerologie Thoracique
Investigators
Principal Investigator: Julien MAZIERES, MD, phD University Hospital, Toulouse
  More Information

Additional Information:
No publications provided

Responsible Party: Intergroupe Francophone de Cancerologie Thoracique
ClinicalTrials.gov Identifier: NCT01556191     History of Changes
Other Study ID Numbers: IFCT-1003
Study First Received: March 8, 2012
Last Updated: November 29, 2013
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by Intergroupe Francophone de Cancerologie Thoracique:
lung cancer
women

Additional relevant MeSH terms:
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Estrogen Antagonists
Fulvestrant
Estrogen Receptor Modulators
Estrogens
Gefitinib
Erlotinib
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hormones
Antineoplastic Agents
Therapeutic Uses
Antineoplastic Agents, Hormonal
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014