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

Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00589238
• Other study ID #: CDR0000579522
• Secondary ID: SINGAPORE-NCC-07
• Status: Terminated
• Phase: Phase 2
• First received: January 3, 2008
• Last updated: June 18, 2013
• Start date: January 2008

Study information

• Verified date: June 2013
• Source: National Cancer Centre, Singapore
• Contact: n/a
• Is FDA regulated: No
• Health authority: Singapore: Health Sciences Authority
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. primary completion date: July 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• carboplatin

• cyclophosphamide

• doxorubicin hydrochloride

• paclitaxel

Locations

Country	Name	City	State
Singapore	KK Women's and Children Hospital	Singapore
Singapore	National Cancer Centre - Singapore	Singapore

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Centre, Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pathological complete response rate		Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.	No
Secondary	Clinical and pathological overall response rates		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.	No
Secondary	Overall and disease-free survival		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.	No
Secondary	Incidence of each toxicity item		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.	Yes
Secondary	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		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.	No