Study of Safety and Efficacy of Letrozole Monotherapy as Second-line Endocrine Therapy in Postmenopausal Patients With Advanced Breast Cancer Who Received Previous Anti-estrogen Treatment

Study Overview
=================
Brief Summary
-----------------
Safety and efficacy of letrozole 2.5 mg/day monotherapy as second-line endocrine therapy in postmenopausal patients with advanced breast cancer who received previous anti-estrogen treatment To investigate changes in blood drug concentrations and blood hormone kinetics. To investigate gene polymorphisms of CYP2A6, an enzyme involved in the metabolism of letrozole

Official Title
-----------------
Study of Safety and Efficacy of Letrozole Monotherapy as Second-line Endocrine Therapy in Postmenopausal Patients With Advanced Breast Cancer Who Received Previous Anti-estrogen Treatment

Conditions
-----------------
Postmenopausal Women With Advanced Breast Cancer

Intervention / Treatment
-----------------
* Drug: Letrozole


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with histologically or cytologically documented breast cancer Patients with progressive breast cancer (advanced breast cancer, locoregional recurrence not operative, or metastatic breast cancer) Patients with hormone receptor (ER and/or PgR) positive or both unknown. Postmenopausal patients between ages 20 and 79 years, inclusive Patients with a history of adjuvant therapy or advanced breast cancer treated with anti-estrogens Patients with documented measurable or evaluable lesions. Patients with sufficient organ function to evaluate the safety Patients whose performance status (PS) is 0～2 Exclusion Criteria: Patients with diffuse lymphangitis carcinomatosa of the lung or CNS involvement, liver metastasis occupying more than one third of the liver, or inflammatory breast cancer Patients with other concurrent or previous malignant disease (excluding contralateral breast cancer, in situ carcinoma of cervix uteri, and adequately treated basal or squamous cell carcinoma of the skin) Patients in whom one of the following is the sole manifestation of disease: hilar enlargement, pleural effusion and ascites Patients with only blastic bone metastases or a mixed blastic and lytic bone metastases at the same site and no other measurable or evaluable lesions Patients with serious current disease such as uncontrolled cardiac diseases and/or uncontrolled diabetes mellitus by any medications (including a historical serious cardiac disease) Patients with adrenal insufficiency (treated or untreated) or Cushing's syndrome Patients with any of the following previous treatments Chemotherapy for metastatic and/or locoregional recurrent disease Previous adjuvant endocrine therapy other than ovariectomy, anti-estrogen treatment, LH-RH analogues or radiation castration Previous first-line endocrine therapy (e.g., aromatase inhibitors and gastagens) for the treatment of metastatic and/or locoregional recurrent breast cancer other than anti-estrogen or LH-RH analogues treatment Patients who have not recovered from toxicity caused by previous therapy For patients on investigational drugs, adequate wash-out periods of at least 7 days in the case of topical investigational drugs and at least 30 days in the case of systemic Previous bisphosphonate therapy started within 6 months without any other measurable or evaluable lesions Patients who have not stopped treatment with other anti-estrogen or anti-cancer drugs (other than bisphosphonates) before starting the trial medication Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Letrozole<br> | Drug: Letrozole<br> <br> * Other names: FEM345;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety during treatment |  | Until disease progression or appearance of unacceptable toxicity whichever comes first | 
| Response Rate during treatment |  | Until disease progression or appearance of unacceptable toxicity whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate during treatment |  | Until disease progression or appearance of unacceptable toxicity whichever comes first | 
| Duration of response |  | from the first date of response confirmed and the last date of response confirmed | 
| Time to progression |  | from the first date of response confirmed and the last date of response confirmed | 
| Time to treatment failure |  | from the date of study initiation and the date of disease progression confirmed or discontinuation other than disease progression | 
| Plasma drug concentration from baseline, every 4 weeks until 28 weeks, at 40 weeks and at 52 weeks |  | Baseline, 52 weeks | 
| Plasma estrogens level |  | baseline, 52 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Aromatase inhibitor, letrozole, breast cancer