Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer

Neoadjuvant Epirubicin-cyclophosphamide-S-1 (ECS) Versus Epirubicin-cyclophosphamide-5-FU (ECF) in Local Advanced Breast Cancer

S-1 is a newly developed novel oral dihydrouracil dehydrogenase inhibiting fluoro-pyrimidine drug consisting of i M tegafur (FT), 0.4 M 5-chloro-2, 4-dihydroxypyrimidine (gimeracil), and 1 M potassium oxonate (oteracil), with efficient antitumor activity and low gastrointestinal toxicity. Several studies have proved the safety and efficacy of single agent S-1 in metastatic breast cancer. This study is designed to further investigate and compare the efficacy and safety of Epirubicin-cyclophosphamide-S-1(ECS) vs. Epirubicin-cyclophosphamide-5-fluorouracil (ECF) as neoadjuvant chemotherapy in patients with local advanced breast cancer.

Study Overview

• Status: Unknown
• Conditions: Breast Neoplasms; Neoadjuvant Therapy
• Intervention / Treatment: Drug: S-1; Drug: 5-FU

• Study Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250033
      • the Second Hospital of Shandong Universtity

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:

• Disease characteristic:

  • Histologically confirmed primary breast cancer by core biopsy (Mammotome or bard needle)
  • Disease stage appropriate for neoadjuvant chemotherapy (T≥3cm, N0 or T（2-3cm）N1 or any T, N2)
  • Her-2(-); Ki67≥14%
  • No previous treatment for breast cancer (chemotherapy, endocrinotherapy, radiotherapy)

• Patients characteristic:

  • Female patients, age 18 to 70 years old
  • Performance Status- Eastern Cooperative Oncology Group (ECOG) 0-2
  • Life expectancy of at least 12 weeks
  • Willing to be kept follow-up
  • Functions below are maintained in major organs:
  • Cardiac status:

LVEF: 50% 45% • Haematopoietic status: Leukocyte count: ≥4.0×109/L Neutrophil count: ≥2.0×109/L Platelet count: ≥100×109/L Hemoglobin: ≥80g/L

• Hepatic status: Total Bilirubin ≤ 1.5 x upper limit of normal (ULN), AST and ALT ≤ 2.5 times ULN(no liver metastasis) bilirubin:

• Renal status: BUN ≤ 1.5 x times ULN Creatinine ≤1.5 times ULN or calculated creatinine clearance, using the Cockcroft-Gault formula, ≥50 mL/min; Women's Ccr = Body weight x (140-Age)/(72 x Serum creatinine) x 0.85

• Written informed consent (both biopsy and neoadjuvant chemotherapy) will be obtained for patients for entering this study

Exclusion Criteria:

• Previous treatment for breast cancer (neither local nor systemic therapy)
• Known or suspected distant metastasis
• Potentially pregnant, pregnant, or breast-feeding
• Drug allergy
• Concurrent malignancy or history of other malignancy (except Hodgkin lymphoma)
• Currently active severe infection (Hepatitis included)
• History of significant neurological or psychiatric disorders including psychotic disorders, dementia or seizures
• Known history of uncontrolled severe heart disease, myocardial infarction within 6 months, congestive heart failure, unstable angina pectoris, clinically significant hydropericardium or unstable arrhythmias

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
Experimental: Epirubicin-cyclophosphamide-S-1( ECS); S-1(SuLi,QILU Pharmaceutical co.ltd ) was given at a standard dose of 40 mg/m2 twice daily in cycles of 14-day consecutive administration followed by a 14-day rest, combined with by epirubicin(80mg/m2, d1 and d8 respectively) and cyclophosphamide(500mg/m2, d1, infusion). The chemotherapy was applicated 4 cycles 4-weekly.	Drug: S-1; S-1(SuLi, QILU Pharmaceutical co.ltd ) was given at a standard dose of 40 mg/m2 twice daily in cycles of 14-day consecutive administration; Other Names: SuLi, QILU Pharmaceutical co.ltd
Active Comparator: Epirubicin-cyclophosphamide-5-FU (ECF); 5-FU was given at a standard dose of 500mg/m2 (infusion, d1, d8 respectively), combined with by epirubicin(80mg/m2, d1 and d8 respectively) and cyclophosphamide(500mg/m2, d1, infusion). The chemotherapy was applicated 4 cycles 4-weekly.	Drug: 5-FU; 5-FU was given at a standard dose of 500mg/m2 (infusion, d1, d8 respectively),

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological complete response	Pathological complete response (pCR=ypT0 ypN0) rates of neoadjuvant treatment No microscopic evidence of residual invasive or non-invasive viable tumor cells in all resected specimens of the breast and axilla. Pathological response will be assessed considering all removed breast and lymphatic tissues from all surgeries. The primary endpoint will be summarized as pathological complete remission rate for each treatment group. Ultrasonic examination will be performed every 2 cycles of treatment for efficacy evaluation.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-free Survival	The length of time after primary treatment for a cancer ends that the patient survives without any signs or symptoms of that cancer. Evaluation will be performed every 2 cycles of treatment during therapy, and follow-up will be performed every 3 months after therapy	5 years
Tolerability and safety	Reference to NCI Common Toxicity Criteria for Adverse Effects (CTCAE) v 3.0. The endpoint will be summarized as events rate (%) for each treatment group	12 weeks

Collaborators and Investigators

• Sponsor: Shandong University
• Investigators: Principal Investigator: Gang Z Yu, Dr; PhD, The Second Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start: June 1, 2013
• Primary Completion (Anticipated): October 1, 2013
• Study Completion (Anticipated): June 1, 2018

Study Registration Dates

• First Submitted: May 6, 2013
• First Submitted That Met QC Criteria: May 6, 2013
• First Posted (Estimate): May 8, 2013

Study Record Updates

• Last Update Posted (Estimate): May 8, 2013
• Last Update Submitted That Met QC Criteria: May 6, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Keywords: S-1; Neoadjuvant Chemotherapy; Local Advanced Breast Neoplasms
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: BEST T-01