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Paclitaxel, Doxorubicin, and Cyclophosphamide With Or Without Carboplatin in Treating Women With Locally Advanced Breast Cancer That Can Be Removed by Surgery

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00589238
First received: January 3, 2008
Last updated: June 16, 2009
Last verified: June 2009
History of Changes
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:

U.S. FDA Resources

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

ClinicalTrials.gov Identifier: NCT00589238     History of Changes
Other Study ID Numbers: CDR0000579522, SINGAPORE-NCC-0701
Study First Received: January 3, 2008
Last Updated: June 16, 2009
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

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Doxorubicin
Carboplatin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
 Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 22, 2013