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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00994968
• Other study ID #: CDR0000650694
• Secondary ID: YONSEI-YCC-BR09-
• Status: Recruiting
• Phase: Phase 2
• First received: October 13, 2009
• Last updated: October 28, 2010
• Start date: July 2009

Study information

• Verified date: October 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 49
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• cyclophosphamide

• docetaxel

• doxorubicin hydrochloride

• tegafur-gimeracil-oteracil potassium

Procedure:
• neoadjuvant therapy

• therapeutic conventional surgery

Locations

Country	Name	City	State
Korea, Republic of	Yonsei Cancer Center at Yonsei University Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Yonsei University

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of pathologic complete response			No
Secondary	Safety and tolerability			Yes
Secondary	Rate of overall radiologic response			No
Secondary	Rate of breast-conserving procedure			No
Secondary	Disease-free survival			No
Secondary	Relevant pharmacogenomics and biomarker(s) which may be useful to predict any responses to the anticancer treatments			No