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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: 5-Fluorouracil; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Epirubicin; Drug: Capecitabine

• Study Type: Interventional
• Enrollment (Actual): 182
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bayonne, France, 64100
  • Beziers, France, 34500
  • Bourg En Bresse, France, 01012
  • Colmar, France, 68024
  • Dijon, France, 21079
  • Hyeres, France, 83400
  • La Tronche, France, 38700
  • Le Mans, France, 72037
  • Limoges, France, 87042
  • Lyon, France, 69437
  • Marseille, France, 13385
  • Montbeliard, France, 25209
  • Montfermeil, France, 93370
  • Nice, France, 06189
  • Nimes, France, 30029
  • Paris, France, 75181
  • Pierre Benite, France, 69310
  • Saint Herblain, France, 44805
  • Strasbourg, France, 67010
  • Toulouse, France, 31059
  • Vannes, France, 56001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 5-Fluorouracil + Epirubicin + Cyclophosphamide; 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; 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.; Drug: Cyclophosphamide; 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.; Drug: Docetaxel; 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.; Drug: Epirubicin; 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.
Experimental: Capecitabine + Epirubicin + Cyclophosphamide; 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: Cyclophosphamide; 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.; Drug: Docetaxel; 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.; Drug: Epirubicin; 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.; Drug: Capecitabine; 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.; Other Names: Xeloda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: July 25, 2016
• First Submitted That Met QC Criteria: July 25, 2016
• First Posted (Estimate): July 27, 2016

Study Record Updates

• Last Update Posted (Estimate): July 27, 2016
• Last Update Submitted That Met QC Criteria: July 25, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Docetaxel; Cyclophosphamide; Fluorouracil; Capecitabine; Epirubicin
• Other Study ID Numbers: ML16986