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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

Primary Purpose

Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
Singapore
Study Type
Interventional
Intervention
carboplatin
cyclophosphamide
doxorubicin hydrochloride
paclitaxel
Sponsored by
National Cancer Centre, Singapore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • National Cancer Centre - Singapore
  • KK Women's and Children Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Arm 1 (Standard Arm)

Arm 2 (Experimental Arm)

Arm Description

Arm 1 (Standard Arm) Preoperative (primary/ neoadjuvant) intravenous weekly paclitaxel 80 mg/m2 for 12 weeks followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles.

Arm 2 (Experimental Arm) Preoperative intravenous weekly paclitaxel 80 mg/m2 in combination with carboplatin AUC 2 on D1, D8 and D15 every 28 days for 4 cycles followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles.

Outcomes

Primary Outcome Measures

Pathological complete response rate

Secondary Outcome Measures

Clinical and pathological overall response rates
Overall and disease-free survival
Incidence of each toxicity item
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

Full Information

First Posted
January 3, 2008
Last Updated
June 18, 2013
Sponsor
National Cancer Centre, Singapore
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1. Study Identification

Unique Protocol Identification Number
NCT00589238
Brief Title
Paclitaxel, Doxorubicin, and Cyclophosphamide With Or Without Carboplatin in Treating Women With Locally Advanced Breast Cancer That Can Be Removed by Surgery
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Terminated
Study Start Date
January 2008 (undefined)
Primary Completion Date
July 2012 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Centre, Singapore

4. Oversight

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
16 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1 (Standard Arm)
Arm Type
Other
Arm Description
Arm 1 (Standard Arm) Preoperative (primary/ neoadjuvant) intravenous weekly paclitaxel 80 mg/m2 for 12 weeks followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles.
Arm Title
Arm 2 (Experimental Arm)
Arm Type
Experimental
Arm Description
Arm 2 (Experimental Arm) Preoperative intravenous weekly paclitaxel 80 mg/m2 in combination with carboplatin AUC 2 on D1, D8 and D15 every 28 days for 4 cycles followed by doxorubicin 60 mg/m2 in combination with cyclophosphamide 600 mg/m2 every 21 days for 4 cycles.
Intervention Type
Drug
Intervention Name(s)
carboplatin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
doxorubicin hydrochloride
Intervention Type
Drug
Intervention Name(s)
paclitaxel
Primary Outcome Measure Information:
Title
Pathological complete response rate
Time Frame
Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.
Secondary Outcome Measure Information:
Title
Clinical and pathological overall response rates
Time Frame
Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Title
Overall and disease-free survival
Time Frame
Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Title
Incidence of each toxicity item
Time Frame
Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.
Title
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
Time Frame
Clinical response: Serial 4 weekly clinical examination; Mammography, breast ultrasound: Baseline, 3 weeks after treatment protocol or documented clinical progression. Pathological response: Evaluation of surgical specimen after protocol treatment.

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wong Nan Soon, MBBS, MRCP, FAMS
Organizational Affiliation
National Cancer Centre, Singapore
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ann Lee Siew Gek
Organizational Affiliation
National Cancer Centre, Singapore
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Cancer Centre - Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
KK Women's and Children Hospital
City
Singapore
Country
Singapore

12. IPD Sharing Statement

Learn more about this trial

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

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