Doxorubicin Hydrochloride, Cyclophosphamide, Docetaxel, and S-1 Before Surgery in Treating Women With Stage II or Stage III Breast Cancer

Neoadjuvant Doxorubicin and Cyclophosphamide Followed by Docetaxel and S-1 in Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride, cyclophosphamide, docetaxel, and S-1, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying giving doxorubicin hydrochloride together with cyclophosphamide, docetaxel, and S-1 before surgery in treating women with stage II or stage III breast cancer.

Study Overview

• Status: Unknown
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: cyclophosphamide; Drug: docetaxel; Procedure: therapeutic conventional surgery; Procedure: neoadjuvant therapy; Drug: doxorubicin hydrochloride; Drug: tegafur-gimeracil-oteracil potassium

Detailed Description

OBJECTIVES:

Primary

• Determine the rate of pathologic complete response in women with previously untreated stage II or III breast cancer treated with neoadjuvant doxorubicin hydrochloride and cyclophosphamide followed by docetaxel and S1.

Secondary

• Determine the safety and tolerability of this regimen in these patients.
• Determine the rate of overall radiologic response in these patients.
• Determine the rate of breast-conserving procedures in these patients.
• Determine the disease-free survival of these patients.
• Investigate the relevant pharmacogenomics and biomarker(s) which will be useful to predict any responses to the anticancer treatments.

OUTLINE: Patients receive neoadjuvant doxorubicin hydrochloride IV and cyclophosphamide IV on day 1. Treatment repeats every 3 weeks for up to 4 courses. Patients then receive docetaxel IV over 1 hour on day 1 and oral S-1 on days 1-14. Treatment repeats every 3 weeks for 4 courses. Two to four weeks later, patients undergo surgery to remove the tumor (either breast-conserving procedures or mastectomy). Patients may then undergo radiotherapy and receive endocrine therapy.

• Study Type: Interventional
• Enrollment (Anticipated): 49
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Yonsei Cancer Center at Yonsei University Medical Center
    • Contact: Joo Hyuk Sohn, MD, PhD; Phone Number: 82-2-2228-8130

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed invasive primary breast cancer

  • Clinical (radiologic) stage II or III disease
  • No T4d disease
  • No inflammatory breast cancer

• ErbB2-negative disease OR patient cannot receive trastuzumab treatment

  • ErbB2-positive disease defined as either immunohistochemistry 3+, or FISH- or CISH-positive; immunohistochemistry 2+ is to be determined according to FISH or CISH results

PATIENT CHARACTERISTICS:

• Mobile
• ECOG performance status 0-1
• Normal cardiac function (LVEF > 50%)
• Hemoglobin ≥ 10.0 g/dL
• Absolute neutrophil count ≥ 1,500/μL
• Platelet count ≥ 10 x 10^4/μL
• Creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
• Total bilirubin ≤ 1.5 times ULN
• AST/ALT ≤ 2.5 times ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• Able to swallow tablet whole with water
• No prior motor or sensory neurotoxicity CTCAE ≥ grade 2
• No other serious disease or medical condition

• No uncontrolled or serious cardiovascular disease, including any of the following:

  • Myocardial infarction within the past 6 months
  • New York Heart Association class III or IV heart failure
  • Uncontrolled angina pectoris
  • Clinically significant pericardial disease
  • Cardiac amyloidosis
• No history of symptomatic or therapy-requiring cardiac arrhythmia CTCAE grade 3 (e.g., multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation)
• No asymptomatic sustained ventricular tachycardia
• History of atrial fibrillation or cardiac arrhythmia controlled by medication allowed
• No uncontrolled infection, unstable peptic ulcer, uncontrolled diabetes, or any other contraindication to corticosteroid administration
• No history of infection or any other serious medical event which may cause any functional injury in the affected patient and consequently, interfere with continuing the study treatment
• No history of hypersensitivity to taxanes, fluorouracil, or S-1
• No significant gastrointestinal malfunction that will affect S-1 absorption
• No history of other cancer within the past 5 years except properly treated carcinoma in situ of the uterine cervix or basal cell or squamous cell carcinoma of the skin
• No severe psychological or neurological disorder or dementia that would preclude understanding of the informed consent
• No psychological, social, family, or geographical condition, or difficult circumstance that would preclude follow-up or compliance with the protocol

PRIOR CONCURRENT THERAPY:

• No prior systemic treatment for this cancer (e.g., radiotherapy, chemotherapy, hormone therapy, or biological therapy)
• No prior preoperative topical treatments (e.g., incomplete surgery or radiotherapy) for this cancer

• No concurrent drug(s) that may potentially cause changes in the pharmacological activity of S-1 formulation, including any of the following:

  • Allopurinol
  • Phenytoin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Rate of pathologic complete response

Secondary Outcome Measures

Outcome Measure
Safety and tolerability
Disease-free survival
Rate of overall radiologic response
Rate of breast-conserving procedure
Relevant pharmacogenomics and biomarker(s) which may be useful to predict any responses to the anticancer treatments

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Joo Hyuk Sohn, MD, PhD, Severance Hospital

Publications and helpful links

General Publications

• Moon YW, Lee S, Park BW, Kim EK, Kim SI, Koo JS, Park S, Kim MJ, Chung HC, Kim JH, Sohn J. S-1 combined with docetaxel following doxorubicin plus cyclophosphamide as neoadjuvant therapy in breast cancer: phase II trial. BMC Cancer. 2013 Dec 6;13:583. doi: 10.1186/1471-2407-13-583.

Study record dates

Study Major Dates

• Study Start: July 1, 2009

Study Registration Dates

• First Submitted: October 13, 2009
• First Submitted That Met QC Criteria: October 13, 2009
• First Posted (Estimate): October 14, 2009

Study Record Updates

• Last Update Posted (Estimate): October 29, 2010
• Last Update Submitted That Met QC Criteria: October 28, 2010
• Last Verified: October 1, 2009

More Information

Terms related to this study

• Keywords: stage II breast cancer; stage III breast cancer
• 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; Doxorubicin; Liposomal doxorubicin; Tegafur
• Other Study ID Numbers: CDR0000650694; YONSEI-YCC-BR09-01