Combination Chemotherapy With or Without Trastuzumab in Treating Patients With Stage II or Stage III Breast Cancer

September 14, 2025 updated by: City of Hope Medical Center

Randomized Phase II Study of Docetaxel, Adriamycin, and Cytoxan (TAC) Versus Adriamycin/Cytoxan, Followed by Abraxane/Carboplatin (ACAC) +/- Trastuzumab as Neoadjuvant Therapy for Patients With Stage II-III Breast Cancer

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving combination chemotherapy with or without trastuzumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed. It is not yet known whether combination chemotherapy is more effective with or without trastuzumab in treating breast cancer.

PURPOSE: This randomized phase II trial is comparing two different regimens of combination chemotherapy given together with or without trastuzumab to see how well they work in treating patients with stage II or stage III breast cancer.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Compare 2 neoadjuvant chemotherapy regimens (docetaxel, doxorubicin hydrochloride, and cyclophosphamide [TAC] vs doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin [ACAC]), in terms of toxicities and effectiveness as defined by the pathological complete remission rate, in patients with non HER2/neu overexpressing stage II or III breast cancer.
  • Evaluate the probability of achieving a pathological complete remission when adding trastuzumab (Herceptin®) to ACAC in the subset of patients with HER2/neu overexpressing stage II or III breast cancer.

Secondary

  • Identify prognostic and predictive markers of outcome, recurrence, and targets of therapy.

OUTLINE: This is a randomized study. Patients with non HER2/neu overexpressing tumors are randomized to 1 of 2 treatment arms. Patients with HER2/neu overexpressing tumors are assigned to arm III.

  • Arm I: Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses.
  • Arm II: Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses.
  • Arm III: Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin.

Within 4 weeks after completion of chemotherapy with or without trastuzumab (Herceptin®), all patients undergo surgery.

PROJECTED ACCRUAL: A total of 105 patients will be accrued for this study.

Study Type

Interventional

Enrollment (Actual)

121

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010-3000
        • City of Hope Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

DISEASE CHARACTERISTICS:

  • Histologically proven infiltrating ductal or lobular breast carcinoma

    • Stage II or III disease
    • Inflammatory breast cancer allowed
  • Hormone-receptor status not specified

PATIENT CHARACTERISTICS:

  • ECOG performance status < 2
  • Male or female
  • Menopausal status not specified (for female patients)
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Bilirubin normal (except for patient's with Gilbert's disease)
  • Creatinine ≤ 1.2 mg/dL
  • Creatinine clearance ≥ 70 mL/min
  • Ejection fraction ≥ 50% on MUGA
  • No neuropathy ≥ grade 1
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective nonhormonal contraception

  • No prior malignant disease within the past 5 years, excluding:

    • Squamous cell or basal cell skin carcinoma
    • Stage I or in situ cervical carcinoma
  • No noninvasive (in situ) breast carcinoma within the past 5 years

PRIOR CONCURRENT THERAPY:

  • At least 5 years since prior antiestrogen treatment for any indication other than breast cancer prevention (tamoxifen, raloxifene, or an aromatase inhibitor)
  • No prior radiotherapy to the chest wall

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Docetaxel, Doxorubicin Hydrochloride, and Cyclophosphamide
Patients receive doxorubicin hydrochloride IV, cyclophosphamide IV, and docetaxel IV on day 1. Treatment repeats every 21 days for 6 courses.
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Drug: docetaxel
Given IV
Experimental: Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel and Carboplatin
Patients receive doxorubicin hydrochloride IV and cyclophosphamide IV on day 1; treatment repeats every 2 weeks for 4 courses. Patients then receive carboplatin IV on day 1 and paclitaxel IV on days 1, 8, and 15; treatment with carboplatin and paclitaxel repeats every 4 weeks for 3 courses.
Drug: Carboplatin
Given IV
Drug: Paclitaxel
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV
Experimental: Doxorubicin Hydrochloride and Cyclophosphamide Followed by Paclitaxel, Carboplatin and trastuzumab
Patients receive chemotherapy as in arm II. They also receive trastuzumab (Herceptin®) IV weekly, beginning with the first doses of paclitaxel and carboplatin.
Drug: Carboplatin
Given IV
Biological: Trastuzumab
Given IV
Drug: Paclitaxel
Given IV
Drug: cyclophosphamide
Given IV
Drug: doxorubicin hydrochloride
Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Count of Patients With Pathologic Complete Response (pCR)
Time Frame: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months
pCR was defined as no evidence of residual invasive cancer (or very few scattered tumor cells) in primary tumor and lymph nodes.
At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months
Count of Patients With Residual Cancer Burden (RCB) Scores of 0 or 1.
Time Frame: At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months.

RCB score is determined using information on the size of the tumor and the extent of tumor cells in the breast and axillary lymph nodes after neoadjuvant therapy. The higher the RCB score, the more residual breast cancer there is in the breast and lymph nodes:

RCB-0 = No residual breast cancer RCB-I = Small amount of residual breast cancer RCB-II = Moderate amount of residual breast cancer RCB-III = Extensive (a lot of) residual breast cancer
At the time of surgery within 4 weeks of the end of chemotherapy, up to 10 months.

Secondary Outcome Measures

Outcome Measure
Time Frame
Quality of life and neuropathy assessment of prognostic and predictive markers as measured by FACT exploratory methods at 1 year
Time Frame: 1 year post treatment
1 year post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Joanne Mortimer, MD, City of Hope Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 27, 2005

Primary Completion (Actual)

December 30, 2013

Study Completion (Estimated)

August 11, 2026

Study Registration Dates

First Submitted

February 23, 2006

First Submitted That Met QC Criteria

February 23, 2006

First Posted (Estimated)

February 24, 2006

Study Record Updates

Last Update Posted (Estimated)

September 25, 2025

Last Update Submitted That Met QC Criteria

September 14, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 05015
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CDR0000455631 (Registry Identifier: PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe