Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	Genentech
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00038402

Purpose

The purpose of this study is to evaluate the addition of Herceptin to standard chemotherapy treatment of patients newly diagnosed with operable breast cancer.

Other objectives: 1) to evaluate the potential of this therapy to reduce the size of the tumor and increase the possibility of breast conservative surgery, 2) evaluate the ability of this regimen to prevent recurrence of breast cancer and impact on survival, 3) determine side effect profile with the addition of Herceptin, and 4) evaluate significance of HER2 expression by two different methods.

Condition	Intervention	Phase
Breast Cancer	Drug: Herceptin Drug: Taxol Drug: Fluorouracil Drug: Cytoxan Drug: Epirubicin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer

Drug Information available for: Cyclophosphamide Fluorouracil Paclitaxel Epirubicin hydrochloride Epirubicin Trastuzumab

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Number of Participants Achieved Pathological Complete Remission [ Time Frame: Baseline to last treatment cycle (approximately 28 weeks, 4 cycles of 21-day intervals of Taxol and up to 4 cycles of FEC for 3-4 week intervals) ] [ Designated as safety issue: No ]
Response criteria for Complete Remission defined as disappearance of all clinical evidence of active tumor by clinical evaluation, mammogram and/or ultrasound, and free of all symptoms.

Enrollment:	74
Study Start Date:	April 2001
Study Completion Date:	July 2011
Primary Completion Date:	July 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Herceptin + Taxol Followed by FEC Herceptin starting 4 mg/kg intravenous (IV), then 2 mg/kg weekly for all other cycles neo-adjuvant chemotherapy and during FEC therapy for total 24 doses. Taxol 225 mg/m^2 continuous IV over 24 hours each cycle; Fluorouracil 500 mg/m^2 IV Days 1 at 3-4 week intervals; Cytoxan 500 mg/m^2 IV on Day 1; Epirubicin 75 mg/m^2 IV on Day 1. Four 21-day cycles.	Drug: Herceptin Starting dose of 4 mg/kg by vein, then 2 mg/kg weekly after that until the end of all cycles of neo-adjuvant chemotherapy and during FEC therapy for a total of 24 doses. Other Name: Trastuzumab Drug: Taxol 225 mg/m^2 by vein as a continuous infusion over 24 hours each cycle for a total of 4 cycles. Other Name: Paclitaxel Drug: Fluorouracil 500 mg/m^2 by vein on Days 1 and 4 for 4 cycles at 3-4 week intervals. Drug: Cytoxan 500 mg/m^2 on Day 1 of each cycle for 4 cycles. Other Names: Cyclophosphamide Neosar Drug: Epirubicin 75 mg/m^2 IV on Day 1 of each cycle for 4 cycles.

Arms

Assigned Interventions

Experimental: Herceptin + Taxol Followed by FEC

Herceptin starting 4 mg/kg intravenous (IV), then 2 mg/kg weekly for all other cycles neo-adjuvant chemotherapy and during FEC therapy for total 24 doses. Taxol 225 mg/m^2 continuous IV over 24 hours each cycle; Fluorouracil 500 mg/m^2 IV Days 1 at 3-4 week intervals; Cytoxan 500 mg/m^2 IV on Day 1; Epirubicin 75 mg/m^2 IV on Day 1. Four 21-day cycles.

Drug: Herceptin

Starting dose of 4 mg/kg by vein, then 2 mg/kg weekly after that until the end of all cycles of neo-adjuvant chemotherapy and during FEC therapy for a total of 24 doses.

Other Name: Trastuzumab

Drug: Taxol

225 mg/m^2 by vein as a continuous infusion over 24 hours each cycle for a total of 4 cycles.

Other Name: Paclitaxel

Drug: Fluorouracil

500 mg/m^2 by vein on Days 1 and 4 for 4 cycles at 3-4 week intervals.

Drug: Cytoxan

500 mg/m^2 on Day 1 of each cycle for 4 cycles.

Other Names:

Cyclophosphamide
Neosar

Drug: Epirubicin

75 mg/m^2 IV on Day 1 of each cycle for 4 cycles.

Show Detailed Description

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

All patients with histologic confirmation of invasive, but non-inflammatory carcinoma of the breast with T2-3 (greater than 2 cm), N0-1, M0 will be eligible. Patients with T1N1 (after histological confirmation of nodal disease) will be eligible for the study.
Histologic confirmation of invasive tumor will be done by core needle biopsy. On the tissue obtained, estrogen and progesterone receptors (ER/PR) as well as Her-2/neu (will be determined by immunohistochemistry (IH) and/or fluorescence in situ hybridization (FISH)) and p53 will be done (for research evaluation). Tumor proliferation rate will be evaluable by immunohistochemistry using paraffin-embedded sections and monoclonal antibody for ki-67. Residual tumor tissue will be saved in the tissue bank for further future studies.
All patients who are Her-2/neu positive will be eligible for the study. Her-2/neu positivity for protocol purposes will be determined by IHC and patients with tumors that are 3+ or FISH + will be eligible.
Patients must sign an informed consent indicating that they are aware of the investigational nature of the study, in keeping with institutional policy.
All patients should have adequate bone marrow function, as defined by peripheral granulocyte count of >1,500/mm3, and platelet count > 100,000 mm3. Patients must have adequate liver function, with a bilirubin within normal laboratory values. In addition, patients should have adequate renal function, defined as serum creatinine <2.0 mg%.
Patients must have a normal cardiac ejection fraction as determined by baseline echocardiogram. Tape must be saved for review by central cardiologist.
Patients who underwent biopsy outside will be eligible if they had a measurable residual tumor.
Patients with multicentric disease and extensive Ductal Carcinoma in Situ (DCIS) will be eligible for study.
Patients with a history of cardiac arrhythmia will be eligible for study after being cleared by cardiology.

Exclusion Criteria:

Patients with T1N0 disease are not eligible for the study.
Those patients with history of other invasive malignancies will be excluded except non-melanoma skin cancer and non-invasive cervical cancer.
Patients with a history of congestive heart failure will be excluded.
Patients who had surgical therapy prior to referral will be ineligible.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00038402

Locations

United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030

Sponsors and Collaborators

M.D. Anderson Cancer Center

Genentech

Investigators

Principal Investigator:

Aman U Buzdar, MD

M.D. Anderson Cancer Center

More Information

Additional Information:

The University of Texas M.D.Anderson Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Aman U. Buzdar, MD/Professor, U.T. M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00038402 History of Changes
Other Study ID Numbers:	ID99-146
Study First Received:	May 30, 2002
Last Updated:	August 10, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by M.D. Anderson Cancer Center:

Breast Cancer
Non-Inflammatory Breast Cancer
Operable Breast Cancer
Herceptin
Taxol
FEC

Fluorouracil
Cyclophosphamide
Epirubicin
Trastuzumab
Paclitaxel
Neosar

Additional relevant MeSH terms:

Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Trastuzumab
Epirubicin
Paclitaxel
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antimetabolites
Antimetabolites, Antineoplastic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 09, 2012