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A Randomised Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide Compared to Doxorubicin and Cyclophosphamide in Operable Node Negative Breast Cancer With Normal Topoisomerase IIα Expression

Phase 2
21 Years
Open (Enrolling)
Breast Cancer

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Trial Information

A Randomised Phase 2 Study of Neoadjuvant Docetaxel and Cyclophosphamide Compared to Doxorubicin and Cyclophosphamide in Operable Node Negative Breast Cancer With Normal Topoisomerase IIα Expression



- 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


- 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

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.

Inclusion Criteria


- 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


- 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

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia

- Psychiatric illness/social situations that would limit compliance with study

- No prior malignancies except curatively treated basal cell carcinoma of the skin or
carcinoma in situ of the cervix


- 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

Type of Study:


Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Pathological complete response rate

Safety Issue:


Principal Investigator

Wong Nan Soon, MBBS, MRCP, FAMS

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Centre, Singapore



Study ID:




Start Date:

October 2008

Completion Date:

Related Keywords:

  • Breast Cancer
  • stage II breast cancer
  • Breast Neoplasms