Chemotherapy Plus Monoclonal Antibody Therapy in Treating Women With Stage II or Stage IIIA Breast Cancer That Overexpresses HER2

May 31, 2013 updated by: National Cancer Institute (NCI)

Pilot Trial of Paclitaxel-Herceptin Adjuvant Therapy for Early Stage Breast Cancer

Randomized phase II trial to study the effectiveness of chemotherapy with paclitaxel and the monoclonal antibody trastuzumab followed by chemotherapy in treating women who have stage II or stage IIIA breast cancer that overexpresses HER2. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies can locate tumor cells and deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with chemotherapy may kill more tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

I. Evaluate the safety of paclitaxel plus trastuzumab (Herceptin) followed by adjuvant chemotherapy in women with node positive stage II or IIIa breast cancer with HER2 overexpression.

II. Evaluate the safety of long term trastuzumab (Herceptin) in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to radiotherapy (none planned vs planned to breast or chest wall). Patients are randomized to one of two treatment arms.

ARM I: Patients receive paclitaxel IV over 3 hours immediately followed by trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Paclitaxel repeats every 3 weeks for 4 courses and trastuzumab (Herceptin) repeats weekly for 10 courses. At 3 weeks following paclitaxel and trastuzumab (Herceptin), patients receive doxorubicin IV and cyclophosphamide IV over 1 hour every 3 weeks for 4 courses. Following chemotherapy, estrogen receptor (ER) positive and/or progesterone receptor (PR) positive patients receive oral tamoxifen twice daily for 5 years.

ARM II: Patients receive same therapy as in Arm I, except for additional trastuzumab (Herceptin) IV weekly beginning within 3 weeks following completion of chemotherapy and local therapy and continuing for 1 year. ER and/or PR positive patients receive tamoxifen as in Arm I but may be concurrent with trastuzumab (Herceptin). Following completion of doxorubicin and cyclophosphamide, post lumpectomy and post mastectomy patients may receive local radiotherapy daily for 5-6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 200 patients (100 per treatment arm) will be accrued for this study within 1 year.

Study Type

Interventional

Enrollment (Actual)

200

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

  • South Africa
      • Pretoria, South Africa, 0001
        • Pretoria Academic Hospital
  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Veterans Affairs Medical Center - Palo Alto
      • Stanford, California, United States, 94305-5408
        • Stanford University Medical Center
    • Colorado
      • Denver, Colorado, United States, 80209-5031
        • CCOP - Colorado Cancer Research Program, Inc.
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University Hospital - Atlanta
      • Decatur, Georgia, United States, 30033
        • Veterans Affairs Medical Center - Atlanta (Decatur)
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Robert H. Lurie Comprehensive Cancer Center, Northwestern University
      • Chicago, Illinois, United States, 60611
        • Veterans Affairs Medical Center - Chicago (Lakeside)
      • Decatur, Illinois, United States, 62526
        • CCOP - Central Illinois
      • Evanston, Illinois, United States, 60201
        • CCOP - Evanston
      • Peoria, Illinois, United States, 61602
        • CCOP - Illinois Oncology Research Association
      • Urbana, Illinois, United States, 61801
        • CCOP - Carle Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Veterans Affairs Medical Center - Indianapolis (Roudebush)
    • Iowa
      • Cedar Rapids, Iowa, United States, 52403-1206
        • CCOP - Cedar Rapids Oncology Project
    • Kansas
      • Wichita, Kansas, United States, 67214-3882
        • CCOP - Wichita
    • Louisiana
      • New Orleans, Louisiana, United States, 70121
        • CCOP - Ochsner
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Johns Hopkins Oncology Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02111
        • New England Medical Center Hospital
    • Michigan
      • Ann Arbor, Michigan, United States, 48106
        • CCOP - Ann Arbor Regional
      • Kalamazoo, Michigan, United States, 49007-3731
        • CCOP - Kalamazoo
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
      • Saint Louis Park, Minnesota, United States, 55416
        • CCOP - Metro-Minnesota
    • Nebraska
      • Omaha, Nebraska, United States, 68131
        • CCOP - Missouri Valley Cancer Consortium
    • New Jersey
      • Elizabeth, New Jersey, United States, 07201
        • Trinitas Hospital - Jersey Street Campus
      • Flemington, New Jersey, United States, 08822
        • Hunterdon Regional Cancer Program
      • Hackensack, New Jersey, United States, 07601
        • Hackensack University Medical Center
      • Hackensack, New Jersey, United States, 07601
        • CCOP - Northern New Jersey
      • Morristown, New Jersey, United States, 07962-1956
        • Morristown Memorial Hospital
    • New York
      • Albany, New York, United States, 12208
        • Veterans Affairs Medical Center - Albany
      • Bronx, New York, United States, 10461
        • Albert Einstein Comprehensive Cancer Center
      • New York, New York, United States, 10016
        • Kaplan Cancer Center
      • New York, New York, United States, 10010
        • Veterans Affairs Medical Center - New York
      • Rochester, New York, United States, 14642
        • University of Rochester Cancer Center
    • North Dakota
      • Fargo, North Dakota, United States, 58122
        • CCOP - Merit Care Hospital
    • Ohio
      • Cleveland, Ohio, United States, 44106-5065
        • Ireland Cancer Center
    • Oklahoma
      • Tulsa, Oklahoma, United States, 74136
        • CCOP - Sooner State
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania Cancer Center
      • Wynnewood, Pennsylvania, United States, 19096
        • CCOP - MainLine Health
    • Tennessee
      • Nashville, Tennessee, United States, 37232-6838
        • Vanderbilt Cancer Center
    • Wisconsin
      • Madison, Wisconsin, United States, 53705
        • Veterans Affairs Medical Center - Madison
      • Madison, Wisconsin, United States, 53792
        • University of Wisconsin Comprehensive Cancer Center
      • Milwaukee, Wisconsin, United States, 53226
        • Medical College of Wisconsin
      • Milwaukee, Wisconsin, United States, 53295
        • Veterans Affairs Medical Center - Milwaukee (Zablocki)

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • Histologically confirmed stage II or IIIa (T1-T3, N1-N2, M0) adenocarcinoma of the breast HER2 overexpression (2-3+ by immunochemistry)
  • Bilateral breast cancer allowed
  • Must have had local breast cancer surgery within past 12 weeks
  • Mastectomy or lumpectomy with clear surgical margins AND axillary lymph node dissection with at least 6 nodes removed
  • Hormone receptor status: Not specified

PATIENT CHARACTERISTICS:

  • Age: 18 and over
  • Sex: Female
  • WBC at least 3,000/mm3
  • Platelet count at least 100,000/mm3
  • Hemoglobin at least 9 g/dL
  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • Creatinine no greater than 1.5 times ULN
  • LVEF at least 50%
  • No history of congestive cardiomyopathy
  • No congestive heart failure or myocardial infarction within the past 6 months
  • No uncontrolled hypertension
  • No uncontrolled arrhythmia within the past 6 months
  • No other prior malignancy within the past 5 years except curatively treated basal or squamous cell skin cancer or carcinoma in situ of the cervix
  • No other serious medical illness that would limit survival to less than 2 years
  • No psychiatric condition precluding study
  • Not pregnant or nursing
  • Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy for breast cancer
  • No prior hormonal therapy for breast cancer
  • At least one year since prior tamoxifen for chemoprevention (e.g., Breast Cancer Prevention Trial)
  • No prior radiotherapy to the breast, chest wall, or regional lymph nodes

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
Experimental: Arm I
Patients receive paclitaxel IV over 3 hours immediately followed by trastuzumab (Herceptin) IV over 30-90 minutes on day 1. Paclitaxel repeats every 3 weeks for 4 courses and trastuzumab (Herceptin) repeats weekly for 10 courses. At 3 weeks following paclitaxel and trastuzumab (Herceptin), patients receive doxorubicin IV and cyclophosphamide IV over 1 hour every 3 weeks for 4 courses. Following chemotherapy, estrogen receptor (ER) positive and/or progesterone receptor (PR) positive patients receive oral tamoxifen twice daily for 5 years.
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Biological: trastuzumab
Drug: tamoxifen citrate
Experimental: Arm II
Patients receive same therapy as in Arm I, except for additional trastuzumab (Herceptin) IV weekly beginning within 3 weeks following completion of chemotherapy and local therapy and continuing for 1 year. ER and/or PR positive patients receive tamoxifen as in Arm I but may be concurrent with trastuzumab (Herceptin). Following completion of doxorubicin and cyclophosphamide, post lumpectomy and post mastectomy patients may receive local radiotherapy daily for 5-6 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: paclitaxel
Biological: trastuzumab

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

  • Sledge GW, O'Neill A, Thor A, et al.: Adjuvant trastuzumab: long-term results of E2198. [Abstract] Breast Cancer Res Treat 100 (Suppl 1): A-2075, S106, 2006.

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

August 1, 1999

Primary Completion (Actual)

January 1, 2007

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

November 1, 1999

First Submitted That Met QC Criteria

June 8, 2004

First Posted (Estimate)

June 9, 2004

Study Record Updates

Last Update Posted (Estimate)

June 3, 2013

Last Update Submitted That Met QC Criteria

May 31, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02305
  • E-2198
  • CDR0000067197 (Registry Identifier: PDQ (Physician Data Query))

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.

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