Docetaxel and Carboplatin With or Without Trastuzumab Before Surgery in Treating Women With Locally Advanced Breast Cancer

Neoadjuvant Treatment and Molecular Characterization of Locally Advanced Breast Cancer

RATIONALE: Drugs used in chemotherapy, such as docetaxel and carboplatin, use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies, such as trastuzumab, can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. It is not yet known whether docetaxel and carboplatin are more effective with or without trastuzumab in treating breast cancer.

PURPOSE: This randomized phase II trial is studying how well giving docetaxel together with carboplatin and trastuzumab before surgery works compared to docetaxel and carboplatin alone before surgery in treating women with locally advanced breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Biological: trastuzumab; Drug: carboplatin; Drug: docetaxel; Biological: trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Pomona, California, United States, 91767-3021
      • Wilshire Oncology Medical Group, Incorporated - Pomona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Confirmed infiltrating adenocarcinoma of the breast
• Primary breast cancer > 5cm, or skin/chest wall involvement, any N, without evidence of metastasis.
• No prior radiation to the involved breast
• ECOG (Electrocochleography) performance status 0-2
• Age 18 years to 80 years
• Absolute Neutrophil count > 1500 cell/μl, platelet count > 100000 cells/μl and hemoglobin > 9 g/dl
• All liver function tests < upper limit of normal
• Serum creatinine < 2.0 mg/dl
• Normal left ventricular ejection fraction (LVEF) as determined by MUGA (Multiple Gated Acquisition) scan or echocardiogram
• HER-2/neu status is determined by a FISH (Fluorescence in situ hybridization) test. [FISH (+) is HER-2/neu (+)]
• If female of childbearing potential, pregnancy test is negative
• If premenopausal and not surgically sterilized, the patient agrees to use effective birth control method for the duration of the study
• Informed consent has been obtained

Exclusion Criteria:

• Non-confirmed infiltrating adenocarcinoma breast cancer
• Evidence of metastasis
• Previous chemotherapy using the drugs proposed in this study, specifically Herceptin®, Taxotere®, and/or Carboplatin
• Prior radiation to the involved breast
• Recent breast cancer drug therapy within last 5 years of any form
• History of allergy to polysorbate or castor oil
• Ongoing active infection
• Concurrent life-limiting disease with a life expectancy of less than one year
• Past or current history of other malignancy within the past 5 years which could affect the diagnosis or assessment of breast cancer, except for curatively treated non-melanoma skin cancer and/or in situ carcinoma of the cervix
• Pregnancy, nursing, fertile women who do not use birth control device
• Inability to give informed consent
• Patients with pre-existing peripheral neuropathy > grade 2

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (neoadjuvant therapy); see intervention description	Biological: trastuzumab; Cycle 5-7 post-op only Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV; Other Names: Herceptin; Drug: carboplatin; Cycle 1-8 Day 1 or 2 AUC = 6 IV; Drug: docetaxel; Cycle 1-8 Day 1 or 2: 75 mg/m2 IV; Other Names: Taxotere; Biological: trastuzumab; Cycle 1-4 pre-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 5-7 post-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV; Other Names: Herceptin
Experimental: Arm II (neoadjuvant therapy); please see intervention description	Biological: trastuzumab; Cycle 5-7 post-op only Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV; Other Names: Herceptin; Drug: carboplatin; Cycle 1-8 Day 1 or 2 AUC = 6 IV; Drug: docetaxel; Cycle 1-8 Day 1 or 2: 75 mg/m2 IV; Other Names: Taxotere; Biological: trastuzumab; Cycle 1-4 pre-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 5-7 post-op Day 1 4mg/kg IV Day 8, 15 2mg/kg IV Cycle 8 Day 1, 8, 15 2mg/kg IV Day 22 6mg/kg IV; Other Names: Herceptin
Experimental: HER2/neu negative patients; please see intervention description	Drug: carboplatin; Cycle 1-8 Day 1 or 2 AUC = 6 IV; Drug: docetaxel; Cycle 1-8 Day 1 or 2: 75 mg/m2 IV; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Objective Response Rate of Patients Treated With Taxotere/Carboplatin With or Without Herceptin Preoperatively.	Objective response rate of patients treated with Taxotere/carboplatin with or without Herceptin preoperatively. Objective response equals the combination of complete response (CR), partial response (PR) and marginal response (MR). Tumor size was assessed by (1) physical examination, (2) mammography and (3) MRI. 5 response groups: complete response (CR), partial response (PR), marginal response (MR), stable disease (SD) & disease progression (DP). Pathologic response assigned into 2 groups: pCR and non-pCR. pCR-no evidence of residual invasive disease in specimen.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Tumor Response by Physical Exam and Imaging Studies		5 years
Tumor Response Assessment	Measured by physical examination compared to breast mammography and MRI assessment	5 years
Clinico-histologic Predictors of pCR (Pathologic Complete Response)		5 years
Pathologic Nodal Status	According to Primary Tumor Response Pathologic lymph node status N0 Axillary and other nearby lymph nodes do not have cancer (when looked at under a microscope) N1 Micrometastases (very small clusters of cancer) OR 1-3 axillary lymph nodes have cancer AND/OR Internal mammary nodes have tiny amounts of cancer found on sentinel node biopsy N2 4-9 axillary lymph nodes have cancer OR Internal mammary nodes have cancer, but axillary lymph nodes do not have cancer N3 10 or more axillary lymph nodes have cancer OR Infraclavicular (under the clavicle) nodes have cancer OR Internal mammary nodes have cancer plus 1 or more axillary lymph nodes have cancer OR 4 or more axillary lymph nodes have cancer plus internal mammary nodes have cancer or micrometastases found on sentinel node biopsy OR Supraclavicular (above the clavicle) nodes have cancer	5 years

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: Genentech, Inc.; Aventis Pharmaceuticals
• Investigators: Principal Investigator: Helena R. Chang, MD, PhD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: September 10, 2003
• First Submitted That Met QC Criteria: September 10, 2003
• First Posted (Estimate): September 11, 2003

Study Record Updates

• Last Update Posted (Actual): September 9, 2020
• Last Update Submitted That Met QC Criteria: August 26, 2020
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: stage IIIA breast cancer; stage IIIB breast cancer; stage II breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Immunological; Docetaxel; Carboplatin; Trastuzumab
• Other Study ID Numbers: 99-11-084; CDR0000321924; AVENTIS-GIA-11156; GENENTECH-H2269s