Neoadjuvant ECS Versus ECF in Local Advanced Breast Cancer

• Sponsor: Shandong University
• Information provided by (Responsible Party): Yu-Zhi Gang, Shandong University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Breast Neoplasms; Neoadjuvant Therapy	Drug: S-1; Drug: 5-FU	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 240 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Neoadjuvant Epirubicin-cyclophosphamide-S-1 (ECS) Versus Epirubicin-cyclophosphamide-5-FU (ECF) in Local Advanced Breast Cancer
• Study Start Date: June 2013
• Estimated Primary Completion Date: October 2013
• Estimated Study Completion Date: June 2018

Arms and Interventions

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 Name: 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),

Outcome Measures

Primary Outcome Measures :

1. Pathological complete response [ Time Frame: 12 weeks ]

   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.

Secondary Outcome Measures :

1. Disease-free Survival [ Time Frame: 5 years ]

   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

2. Tolerability and safety [ Time Frame: 12 weeks ]
   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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Gang Z Yu, Dr; PhD; +86 0531-85875048; yzg@medmail.com.cn

Locations

China, Shandong

the Second Hospital of Shandong Universtity; Not yet recruiting

Jinan, Shandong, China, 250033

Contact: Gang Z Yu, Dr; PhD +86 0531-85875048 yzg@medmail.com.cn

Principal Investigator: Gang Z Yu, Dr; PhD

Sponsors and Collaborators

Shandong University

Investigators

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

More Information

• Responsible Party: Yu-Zhi Gang, Director of Department of Breast Disease, Shandong University
• ClinicalTrials.gov Identifier: NCT01849380 History of Changes
• Other Study ID Numbers: BEST T-01
• First Posted: May 8, 2013
• Last Update Posted: May 8, 2013
• Last Verified: May 2013

Keywords provided by Yu-Zhi Gang, Shandong University:

Local Advanced Breast Neoplasms; Neoadjuvant Chemotherapy; S-1

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Cyclophosphamide; Epirubicin; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Enzyme Inhibitors