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

NCT ID: NCT00295893

Last Updated: 2025-09-25

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-09-27
• Study Completion Date: 2026-08-11

Brief Summary

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.

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.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

cyclophosphamide

Intervention Type: DRUG

Given IV

docetaxel

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Paclitaxel

Intervention Type: DRUG

Given IV

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.

Group Type: EXPERIMENTAL

cyclophosphamide

Intervention Type: DRUG

Given IV

doxorubicin hydrochloride

Intervention Type: DRUG

Given IV

Trastuzumab

Intervention Type: BIOLOGICAL

Given IV

Carboplatin

Intervention Type: DRUG

Given IV

Paclitaxel

Intervention Type: DRUG

Given IV

Interventions

cyclophosphamide

Given IV

Intervention Type: DRUG

docetaxel

Given IV

Intervention Type: DRUG

doxorubicin hydrochloride

Given IV

Intervention Type: DRUG

Trastuzumab

Given IV

Intervention Type: BIOLOGICAL

Carboplatin

Given IV

Intervention Type: DRUG

Paclitaxel

Given IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 120 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joanne Mortimer, MD

Role: PRINCIPAL_INVESTIGATOR

City of Hope Medical Center

Locations

City of Hope Medical Center

Duarte, California, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000455631

Identifier Type: REGISTRY

Identifier Source: secondary_id

05015

Identifier Type: -

Identifier Source: org_study_id