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

Phase 2

Terminated

• Conditions: Breast Cancer
• Interventions: Drug: cyclophosphamide; Drug: carboplatin; Drug: doxorubicin hydrochloride; Drug: paclitaxel

• Registration Number: NCT00589238
• Lead Sponsor: National Cancer Centre, Singapore

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.

Study Timeline

• Study Start: 2008-01
• Study First Submitted: 2008-01-03
• Study First Submitted QC: 2008-01-05
• Study First Posted: 2008-01-09
• Primary Completion: 2012-07
• Status Verified: 2013-06
• Last Update Submitted: 2013-06-18
• Last Update Posted: 2013-06-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Female
• Target Recruitment: 16

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1 (Standard Arm)	doxorubicin hydrochloride	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 1 (Standard Arm)	cyclophosphamide	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 1 (Standard Arm)	paclitaxel	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)	carboplatin	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.
Arm 2 (Experimental Arm)	cyclophosphamide	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.
Arm 2 (Experimental Arm)	doxorubicin hydrochloride	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.
Arm 2 (Experimental Arm)	paclitaxel	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.

Primary Outcome Measures

Name	Time	Method
Pathological complete response rate	Pathological response will be assessed by evaluation of surgical specimen after completion of protocol treatment.

Secondary Outcome Measures

Name	Time	Method
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.
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.
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.
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.

Trial Locations

Locations (2)

National Cancer Centre - Singapore; 🇸🇬 Singapore, Singapore

KK Women's and Children Hospital; 🇸🇬 Singapore, Singapore