Paclitaxel, Doxorubicin, and Cyclophosphamide With Or Without Carboplatin in Treating Women With Locally Advanced 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:	NCT00589238

Purpose

RATIONALE: Drugs used in chemotherapy, such as paclitaxel, doxorubicin, cyclophosphamide, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether combination chemotherapy is more effective with or without carboplatin in treating breast cancer.

PURPOSE: This randomized phase II trial is studying giving paclitaxel together with doxorubicin and cyclophosphamide to see how well it works compared to giving paclitaxel together with doxorubicin, cyclophosphamide, and carboplatin in treating women with locally advanced breast cancer that can be removed by surgery.

Condition	Intervention	Phase
Breast Cancer	Drug: carboplatin Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Genetic: microarray analysis Genetic: protein expression analysis Genetic: reverse transcriptase-polymerase chain reaction Other: immunohistochemistry staining method Other: laboratory biomarker analysis Procedure: biopsy Procedure: conventional surgery Procedure: neoadjuvant therapy	Phase II

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Surgery

Drug Information available for: Cyclophosphamide Doxorubicin Doxorubicin hydrochloride Paclitaxel Carboplatin Myocet

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label
Official Title:	Randomised Phase II Trial of Neoadjuvant Weekly Paclitaxel Plus Carboplatin Compared to Weekly Paclitaxel Alone Followed in Both Arms by Doxorubicin and Cyclophosphamide for Operable or Locally Advanced Basal-Like Subtype Breast Cancer Correlating BRCA-1 mRNA and Protein Expression With Carboplatin Response

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 rates [ Designated as safety issue: No ]
Overall and disease-free survival [ Designated as safety issue: No ]
Incidence of each toxicity item [ Designated as safety issue: Yes ]
Correlation between low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK14, basal like gene expression profile, and response to carboplatin based treatment [ Designated as safety issue: No ]

Estimated Enrollment:	72
Study Start Date:	January 2008
Estimated Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

To evaluate tumor pathological complete response rate after neoadjuvant paclitaxel with vs without carboplatin followed by cyclophosphamide and doxorubicin hydrochloride in women with basal-type subtype primary breast cancer.

Secondary

To evaluate the clinical and pathological overall response rate.
To evaluate safety and toxicity.
To evaluate disease-free survival and overall survival.
To correlate low BRCA1 expression (protein and mRNA), p53 mutation, positive CK5/6, positive CK 14, basal-like gene expression profile, and response to carboplatin-based treatment.

OUTLINE: This is a multicenter study. Patients are stratified according to clinical stage (T2-3 vs T4). Patients are randomized to 1 of 2 treatment arms.

Arm I (standard therapy): Patients receive paclitaxel IV over 1 hour once weekly in weeks 1-12. Patients then receive doxorubicin hydrochloride IV and cyclophosphamide IV on days 1, 8, and 15. Treatment with doxorubicin hydrochloride and cyclophosphamide repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Arm II (experimental therapy): Patients receive paclitaxel IV over 1 hour and carboplatin IV over 15 to 20 minutes on days 1, 8, and 15. Treatment with paclitaxel and carboplatin repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients then receive doxorubicin hydrochloride and cyclophosphamide as in arm I. All patients will then undergo surgical resection of the tumor.

Patients undergo biopsy for correlative studies. Samples are analyzed for estrogen receptor and progesterone receptor status, and molecular endpoints (CK 5/6, CK14, p53, BRCA, and EGFR) by RT-PCR, immunohistochemistry, protein expression, and gene expression profiling.

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

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed invasive basal-type breast cancer meeting the following criteria:
- Newly diagnosed disease
- Locally advanced or operable primary disease > 2 cm, without evidence of metastatic disease
- Clinical T2 (> 2 cm), T3 (> 5 cm), or T4 primary tumors with or without clinical lymph node involvement (N0-3)
  - T4 tumors are defined by any of the following:
    - Skin ulceration
    - Satellite nodules
    - Peau d' orange (skin edema)
    - Chest wall invasion
    - Inflammatory breast cancer
Her-2/neu 0-1+ by IHC (or negative by fluorescent in situ hybridization if Her-2 2+ by immunohistochemistry)
No metastatic disease
Hormone receptor status:
- Estrogen and progesterone receptor-negative disease

PATIENT CHARACTERISTICS:

Inclusion criteria:

Female
Menopausal status not specified
ECOG performance status (PS) 0-2 or Karnofsky PS 60-100%
Life expectancy > 10 years
Leukocytes ≥ 3,000/μL
Absolute neutrophil count ≥ 1,500/μL
Platelets ≥ 100,000/μL
Total bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Not pregnant or nursing
Fertile patients must use effective contraception
Cardiac ejection fraction ≥ 50% as assessed by MUGA scan or 2D echocardiogram

Exclusion criteria:

History of allergic reactions attributed to compounds of similar chemical or biologic composition to paclitaxel, carboplatin, or other agents used in the study
Pre-existing peripheral neuropathy
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 or social situations that would limit compliance with study requirements
Prior malignancies except for basal cell carcinoma of the skin or curatively treated carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

No prior chemotherapy or radiotherapy
No HIV-positive patients receiving combination antiretroviral therapy
No concurrent primary growth factor prophylaxis
No other concurrent investigational agents
No other concurrent chemotherapy, immunotherapy, hormonal cancer therapy, surgery for cancer, or experimental medications

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589238

Locations

Singapore
National Cancer Centre - Singapore	Recruiting
Singapore, Singapore, 169610
Contact: Wong Nan Soon, MBBS, MRCP, FAMS 65-6-436-8088

Sponsors and Collaborators

National Cancer Centre, Singapore

Investigators

Principal Investigator:	Wong Nan Soon, MBBS, MRCP, FAMS	National Cancer Centre, Singapore
Principal Investigator:	Ann Lee Siew Gek	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:	CDR0000579522, SINGAPORE-NCC-0701
Study First Received:	January 3, 2008
Last Updated:	February 13, 2009
ClinicalTrials.gov Identifier:	NCT00589238 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Study placed in the following topic categories:

Skin Diseases
Immunologic Factors
Breast Neoplasms
Antimitotic Agents
Cyclophosphamide
Carboplatin
Immunosuppressive Agents
Doxorubicin

Anti-Bacterial Agents
Paclitaxel
Tubulin Modulators
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Alkylating Agents
Breast Diseases

Additional relevant MeSH terms:

Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Cyclophosphamide
Antibiotics, Antineoplastic
Neoplasms by Site
Therapeutic Uses
Alkylating Agents
Breast Diseases
Skin Diseases
Mitosis Modulators
Breast Neoplasms

Carboplatin
Antimitotic Agents
Immunosuppressive Agents
Pharmacologic Actions
Doxorubicin
Neoplasms
Paclitaxel
Tubulin Modulators
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 07, 2009