Evaluation of the Addition of Herceptin to Standard Chemotherapy in the Neoadjuvant Setting for Operable Breast Cancer

NCT00038402 | Completed Phase 3

• 1 other identifier: ID99-146
• Study Type: interventional
• Target: 74
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Non-Inflammatory Breast Cancer; Operable Breast Cancer; Herceptin; Taxol; FEC; Fluorouracil; Cyclophosphamide; Epirubicin; Trastuzumab; Paclitaxel; Neosar

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieved Pathological Complete Remission

  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.

  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)

Study Arms (1)

Herceptin + Taxol Followed by FEC

EXPERIMENTAL

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; Drug: Taxol; Drug: Fluorouracil; Drug: Cytoxan; Drug: Epirubicin

Interventions

Herceptin DRUG

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.

Also known as: Trastuzumab

Herceptin + Taxol Followed by FEC

Taxol DRUG

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

Also known as: Paclitaxel

Herceptin + Taxol Followed by FEC

Fluorouracil DRUG

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

Herceptin + Taxol Followed by FEC

Cytoxan DRUG

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

Also known as: Cyclophosphamide, Neosar

Herceptin + Taxol Followed by FEC

Epirubicin DRUG

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

Herceptin + Taxol Followed by FEC

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator

Study Sites (1)

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• The University of Texas M.D.Anderson Cancer Center

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Paclitaxel; Fluorouracil; Cyclophosphamide; Epirubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Aman U Buzdar, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2002
• First Posted: May 31, 2002
• Study Start: April 1, 2001
• Primary Completion: November 1, 2004
• Study Completion: July 1, 2011
• Last Updated: July 20, 2012

Record last verified: 2012-07

Locations

US (1)