To Evaluate the Efficacy and Safety of Capecitabine Prior to Surgery in Women With Breast Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of treatment with oral capecitabine or intravenous (IV) 5-fluorouracil (5-FU), in combination with epirubicin and cyclophosphamide, prior to surgery in participants with breast cancer. The participants will receive 4 cycles of neoadjuvant Capecitabine + Epirubicin + Cyclophosphamide (CEX) or 5-FU + Epirubicin + Cyclophosphamide (FEC 100) chemotherapy during first treatment period (Period 1, Days 1-85). After 4-6 weeks of the fourth cycle of neoadjuvant chemotherapy (Day 120 +/- 7 days), breast surgery with regional lymph node dissection will be performed, followed within a maximum of 6 weeks by the second treatment period (Period 2, Days 1 to 85) when participants in both study arms will receive 4 cycles of adjuvant docetaxel 100 milligrams per meter square (mg/m^2) by IV infusion on Day 1 of each 21-day cycle. Upon completion of the second treatment period, participants will enter the post-treatment follow-up period which will last for 5 years from the initial date of participant randomization. During this period participants will be evaluated once a year on the anniversary date of randomization.

Official Title
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An Open-Label, Multicenter, Randomized, Phase II Study to Evaluate the Efficacy and Safety of Two Combination Dose Regimens: Capecitabine + Epirubicin + Cyclophosphamide (CEX) Versus 5-FU + Epirubicin + Cyclophosphamide (FEC 100) as Neoadjuvant Therapy in Females Presenting With Operable Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: 5-Fluorouracil
* Drug: Capecitabine
* Drug: Cyclophosphamide
* Drug: Docetaxel
* Drug: Epirubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females with a unilateral, non-inflammatory, non-multicentric, non-metastatic breast adenocarcinoma, not considered candidates for conservative management, and whose diagnosis had been histologically confirmed as T2-3, N0-1, M0 according to the tumor-nodes-metastasis (TNM) classification Clinically or radiologically measurable lesion (in 2 dimensions) Eastern Cooperative Oncology Group (ECOG) performance Status less than equal to (<=) 1 Exclusion Criteria: Females presenting with brain metastases or a neurological or psychiatric disorder which could interfere with proper treatment compliance Previous radiotherapy, chemotherapy, or hormonal therapy for breast cancer Previous history of a malignancy in last 5 years other than cutaneous basal cell carcinoma or carcinoma in situ of the uterine cervix Serious concomitant infection Pregnant or lactating females

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

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 5-Fluorouracil + Epirubicin + Cyclophosphamide<br>Neoadjuvant treatment (Period 1): Participants will receive 4 cycles (cycle length = 21 days) of 5-FU + epirubicin + cyclophosphamide. Surgery will be performed 5 (+/- 1) weeks after the last cycle. Adjuvant treatment (Period 2): Participants will receive 4 cycles (cycle length = 21 days) of docetaxel. | Drug: 5-Fluorouracil<br>* 5-FU will be administered at 500 mg/m^2 by short IV infusion on Day 1 of each 21-day cycle during neoadjuvant treatment period for 4 cycles.<br>Drug: Cyclophosphamide<br>* Cyclophosphamide will be administered at 500 mg/m^2 by short IV infusion on Day 1 of each 21-day cycle for 4 cycles during neoadjuvant treatment period.<br>Drug: Docetaxel<br>* Docetaxel will be administered at 100 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles during adjuvant treatment period.<br>Drug: Epirubicin<br>* Epirubicin will be administered at 100 mg/m^2 by short IV infusion on Day 1 of each 21-day cycle for 4 cycles during neoadjuvant treatment period.<br>|
| Experimental: Capecitabine + Epirubicin + Cyclophosphamide<br>Neoadjuvant treatment (Period 1): Participants will receive 4 cycles (cycle length = 21 days) of capecitabine + epirubicin + cyclophosphamide. Surgery will be performed 5 (+/- 1) weeks after the last cycle. Adjuvant treatment (Period 2): Participants will receive 4 cycles (cycle length = 21 days) of docetaxel. | Drug: Capecitabine<br>* Capecitabine will be administered at 900 mg/m^2 orally twice daily on Days 1-14 of each 21-day cycle for 4 cycles during neoadjuvant treatment period.<br>* Other names: Xeloda;Drug: Cyclophosphamide<br>* Cyclophosphamide will be administered at 500 mg/m^2 by short IV infusion on Day 1 of each 21-day cycle for 4 cycles during neoadjuvant treatment period.<br>Drug: Docetaxel<br>* Docetaxel will be administered at 100 mg/m^2 by IV infusion on Day 1 of each 21-day cycle for 4 cycles during adjuvant treatment period.<br>Drug: Epirubicin<br>* Epirubicin will be administered at 100 mg/m^2 by short IV infusion on Day 1 of each 21-day cycle for 4 cycles during neoadjuvant treatment period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with pathological complete tumor response Assessed by Expert Blinded Independent Review according to the Sataloff classification\n |  | Day 120 +/- 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with pathological complete tumor response Assessed by Investigator according to the Sataloff classification |  | Day 120 +/- 7 days | 
| Percentage of participants with breast conserving surgery |  | Day 120 +/- 7 days | 
| Percentage of participants with objective clinical response, assessed by World Health Organization (WHO) criteria |  | Week 15 | 
| Percentage of participants with clinical response, assessed by WHO criteria |  | Week 15 | 
| Percentage of participants with disease progression, assessed by WHO criteria |  | Baseline up to 29 +/- 1 weeks | 
| Percentage of participants with abnormalities in bilateral mammography |  | Day 85 | 
| Percentage of participants who died |  | Baseline up to 29 +/- 1 weeks | 
| Percentage of participants with abnormal left ventricular ejection fraction (LVEF) |  | Days 1-85 | 
| Percentage of participants with abnormal liver ultrasound |  | Days 1-85 | 
| Percentage of participants with abnormal Chest X-Ray |  | Days 1-85 | 
| Overall survival |  | Baseline up to 5 years | 
| Disease free survival, according to WHO criteria |  | Baseline up to 5 years |