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

Sponsored by:	National Cancer Centre, Singapore
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00801411

Purpose

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.

Condition	Intervention	Phase
Breast Cancer	Drug: cyclophosphamide Drug: docetaxel Drug: doxorubicin hydrochloride	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Myocet Docetaxel

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	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

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Pathological complete response rate [ Designated as safety issue: No ]

Secondary Outcome Measures:

Clinical and pathological overall response rate [ Designated as safety issue: No ]
Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Overall survival [ Designated as safety issue: No ]
Disease-free survival [ Designated as safety issue: No ]

Estimated Enrollment:	318
Study Start Date:	October 2008

Arms	Assigned Interventions
Arm I: Experimental Patients receive cyclophosphamide IV and docetaxel IV over 1 hour on day 1.	Drug: cyclophosphamide Given IV Drug: docetaxel Given IV
Arm II: Active Comparator Patients receive cyclophosphamide IV and doxorubicin hydrochloride IV on day 1.	Drug: cyclophosphamide Given IV Drug: doxorubicin hydrochloride Given IV

Detailed 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.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00801411

Locations

Singapore
National Cancer Centre - Singapore	Recruiting
Singapore, Singapore, 169610
Contact: Wong Nan Soon, MBBS, MRCP, FAMS 65-6-436-8088
Singapore General Hospital	Recruiting
Singapore, Singapore, 169608
Contact: Wong Chow Yin 65-6222-3322

Sponsors and Collaborators

National Cancer Centre, Singapore

Investigators

Principal Investigator:

Wong Nan Soon, MBBS, MRCP, FAMS

National Cancer Centre, Singapore

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000624374, SINGAPORE-NCC0705, SANOFI-AVENTIS-NCC0705
Study First Received:	December 2, 2008
Last Updated:	March 12, 2009
ClinicalTrials.gov Identifier:	NCT00801411 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II breast cancer

Study placed in the following topic categories:

Docetaxel
Anti-Bacterial Agents
Immunologic Factors
Skin Diseases
Breast Neoplasms
Antineoplastic Agents, Alkylating

Cyclophosphamide
Antirheumatic Agents
Alkylating Agents
Immunosuppressive Agents
Doxorubicin
Breast Diseases

Additional relevant MeSH terms:

Molecular Mechanisms of Pharmacological Action
Skin Diseases
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Breast Neoplasms
Cyclophosphamide
Antibiotics, Antineoplastic
Immunosuppressive Agents
Doxorubicin

Pharmacologic Actions
Docetaxel
Neoplasms
Neoplasms by Site
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Alkylating Agents
Breast Diseases

ClinicalTrials.gov processed this record on May 07, 2009