Cyclophosphamide and Docetaxel or Doxorubicin in Treating Women With Newly Diagnosed Breast Cancer That Can Be Removed by Surgery

National Cancer Centre, Singapore

Status and phase

Unknown

Phase 2

Conditions

Breast Cancer

Treatments

Drug: docetaxel

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Study type

Interventional

Funder types

Other

Identifiers

NCT00801411

SINGAPORE-NCC0705

SANOFI-AVENTIS-NCC0705

CDR0000624374

Details and patient eligibility

About

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, docetaxel, and doxorubicin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving combination chemotherapy before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known which chemotherapy regimen is more effective in treating breast cancer.

PURPOSE: This randomized phase II trial is studying cyclophosphamide given together with docetaxel to see how well it works compared with cyclophosphamide given together with doxorubicin in treating women with newly diagnosed breast cancer that can be removed by surgery.

Full description

OBJECTIVES:

Primary

To evaluate tumor pathological complete response rate after neoadjuvant cyclophosphamide in combination with docetaxel vs doxorubicin hydrochloride in women with operable clinically node-negative breast cancer and normal topoisomerase IIα expression.

Secondary

To assess tumor clinical and pathological overall response rates in patients treated with these regimens.
To assess the safety and toxicity of these regimens.
To assess disease-free survival and overall survival of these patients.
To assess the efficacy of short-course (3 days) filgrastim (G-CSF) as primary and secondary prophylaxis against febrile neutropenia in patients receiving docetaxel and cyclophosphamide.

OUTLINE: This is a multicenter study.

Patients are stratified according to hormone receptor status (estrogen receptor [ER]- or progesterone receptor [PR]-positive vs ER- and PR-negative) and T stage (T2 vs T3). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive cyclophosphamide IV and docetaxel IV over 1 hour on day 1.
Arm II: Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1.

In both arms, treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of neoadjuvant chemotherapy, all patients undergo surgery.

Tumor specimens obtained prior to neoadjuvant chemotherapy are analyzed for topoisomerase IIα gene and protein expression by IHC and FISH. Tissue samples are also collected at surgery for future studies.

After completion of study therapy, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

Enrollment

318 estimated patients

Sex

Female

Ages

21+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed invasive breast cancer
- Newly diagnosed disease
- Operable disease
Must have clinical T2 (> 2cm) or T3 (> 5 cm) primary tumors with no clinical lymph node involvement (N0)
- No clinical T4 lesion (e.g., peau d'orange, skin ulceration, satellite nodules, or inflammatory breast cancer)
No evidence of metastatic disease
Known hormone receptor status

PATIENT CHARACTERISTICS:

Menopausal status not specified
ECOG performance status (PS) 0-2 (Karnofsky PS 60-100%)
Life expectancy > 10 years
Leukocytes ≥ 3,000/mm³
ANC ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Total bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine normal or creatinine clearance ≥ 40 mL/min
Normal cardiac ejection fraction, defined as ≥ 50% by MUGA scan or 2D-ECHO
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to docetaxel or other agents used in this study
No history of pre-existing peripheral neuropathy
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness/social situations that would limit compliance with study requirements
No prior malignancies except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy
No other concurrent investigational or commercial agents or therapies with the intent to treat the patient's malignancy
No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, surgery for cancer, or experimental medications
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent antitumor therapy