Letrozole and Metronomic Capecitabine in ER-positive HER2 Negative Advanced Breast Cancer (B-001 Study)

Study Overview
=================
Brief Summary
-----------------
A phase II clinical trial designed to test the effect of combining endocrinal therapy (Letrozole) with chemotherapy (Capecitabine) in first line treatment of advanced cases of female breast cancer with ER positive disease.

Detailed Description
-----------------
This is a randomized clinical trial that assigns patients with female breast cancer in the metastatic entity or advanced -beyond local disease treatment - entity into two arms. Arm A contains Letrozole with metronomic Capecitabine versus arm B that contains Letrozole alone. This is to be applied on ER positive HER2 negative tumours.

Official Title
-----------------
Letrozole With or Without Metronomic Capecitabine in First Line Treatment of Patients With ER-positive HER2 Negative Advanced Breast Cancer: A Randomized Phase II Study.

Conditions
-----------------
Breast Cancer, Estrogen Receptor-positive Breast Cancer, Metastatic Breast Cancer

Intervention / Treatment
-----------------
* Drug: Capecitabine
* Drug: Letrozole 2.5mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female sex Age 18-70 ECOG-PS 0-II. Histopathological proof of breast cancer ER positive (Allred score of ≥3 out of 8), and HER2 negative by IHC (or ISH if HER2 +2). Metastatic/recurrent disease as proven by CT scan, bone scan or clinical examination (for skin lesions). Biopsy of the recurrent lesions is encouraged but not mandatory. Either hormone sensitive setting (Denovo metastatic disease or disease progression after more than 1 year of ending adjuvant endocrine therapy) or secondary resistance to tamoxifen therapy (disease relapse after more than 2 years of starting and less than 1 year of ending adjuvant endocrine therapy, or DP of metastatic disease after more than 6 months of first line tamoxifen). Adequate organ function. Signed informed consent Exclusion criteria: Inadequate organ functions. Disease progression while on prior aromatase inhibitor therapy. Primary endocrine resistance. Double primary cancer (history of other malignancy apart from a non melanoma skin cancer). Refusal to sign consent.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients are assigned into two arms of treatment, arm A contains Letrozole and metronomic Capecitabine while arm B contains Letrozole alone.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemo endocrine treatment (A)<br>Letrozole 2.5mg PO daily + Capecitabine 500mg/m2 bid PO continously | Drug: Capecitabine<br>* Capecitabine metronomic combined with Letrozole<br>* Other names: Xeloda;Drug: Letrozole 2.5mg<br>* Letrozole daily alone<br>* Other names: Femara;|
| Active Comparator: Endocrine treatment only (B)<br>Letrozole 2.5mg PO daily | Drug: Letrozole 2.5mg<br>* Letrozole daily alone<br>* Other names: Femara;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6 months Progression free survival rate | Percentage of patients alive and progression-free at 6 months | 6 months from the start of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate | Rate of CR+PR as assessed by the investigator using RECIST 1.1 criteria | 6 months from the start of treatment | 
| Adverse events rates in both groups | Rates of all grade (grade 1-4) and high grade (grade 3+4) adverse events as assessed by NCI-CTAE v4.0 | 6 months from the start of treatment | 
| Quality of life assessment using FACIT-B questionnare | FACIT-B questionnare will be completed by each patient at baseline and 6 months after randomization | 6 months | 
| Median progression free survival | comparison of estimated median PFS between both groups | 18 months | 
| Time to treatment failure | Time from start treatment to progression, death or treatment discontinuation from any cause | 18 months | 
| Clinical benefit rate | Complete response + partial response + stable disease for 6 months | After 6 months of treatment | 
| Overall survival | Percentage of patients alive at 24 months | 24 months | 
| Time to chemotherapy adminstration | Time from randomization to the first chemotherapy administration | 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Advanced breast cancer, chemo-hormonal, hormone positive, metronomic capecitabine