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

Phase 2
Completed
Conditions
Breast Cancer
Interventions
Registration Number
NCT00003992
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
200
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm ItrastuzumabPatients 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 Itamoxifen citratePatients 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 IItrastuzumabPatients 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.
Arm Idoxorubicin hydrochloridePatients 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 IpaclitaxelPatients 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 IcyclophosphamidePatients 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 IIcyclophosphamidePatients 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.
Arm IIdoxorubicin hydrochloridePatients 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.
Arm IIpaclitaxelPatients 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.
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (45)

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

🇺🇸

Chicago, Illinois, United States

Beth Israel Deaconess Medical Center

🇺🇸

Boston, Massachusetts, United States

CCOP - Kalamazoo

🇺🇸

Kalamazoo, Michigan, United States

CCOP - Northern New Jersey

🇺🇸

Hackensack, New Jersey, United States

Hackensack University Medical Center

🇺🇸

Hackensack, New Jersey, United States

University of Wisconsin Comprehensive Cancer Center

🇺🇸

Madison, Wisconsin, United States

Morristown Memorial Hospital

🇺🇸

Morristown, New Jersey, United States

Vanderbilt Cancer Center

🇺🇸

Nashville, Tennessee, United States

CCOP - Metro-Minnesota

🇺🇸

Saint Louis Park, Minnesota, United States

CCOP - Wichita

🇺🇸

Wichita, Kansas, United States

CCOP - Merit Care Hospital

🇺🇸

Fargo, North Dakota, United States

Veterans Affairs Medical Center - New York

🇺🇸

New York, New York, United States

University of Rochester Cancer Center

🇺🇸

Rochester, New York, United States

CCOP - Illinois Oncology Research Association

🇺🇸

Peoria, Illinois, United States

CCOP - Cedar Rapids Oncology Project

🇺🇸

Cedar Rapids, Iowa, United States

Veterans Affairs Medical Center - Indianapolis (Roudebush)

🇺🇸

Indianapolis, Indiana, United States

Johns Hopkins Oncology Center

🇺🇸

Baltimore, Maryland, United States

University of Pennsylvania Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

Veterans Affairs Medical Center - Chicago (Lakeside)

🇺🇸

Chicago, Illinois, United States

Ireland Cancer Center

🇺🇸

Cleveland, Ohio, United States

New England Medical Center Hospital

🇺🇸

Boston, Massachusetts, United States

Veterans Affairs Medical Center - Palo Alto

🇺🇸

Palo Alto, California, United States

CCOP - Sooner State

🇺🇸

Tulsa, Oklahoma, United States

Trinitas Hospital - Jersey Street Campus

🇺🇸

Elizabeth, New Jersey, United States

CCOP - MainLine Health

🇺🇸

Wynnewood, Pennsylvania, United States

Hunterdon Regional Cancer Program

🇺🇸

Flemington, New Jersey, United States

Veterans Affairs Medical Center - Albany

🇺🇸

Albany, New York, United States

CCOP - Colorado Cancer Research Program, Inc.

🇺🇸

Denver, Colorado, United States

Mayo Clinic Cancer Center

🇺🇸

Rochester, Minnesota, United States

CCOP - Missouri Valley Cancer Consortium

🇺🇸

Omaha, Nebraska, United States

H. Lee Moffitt Cancer Center and Research Institute

🇺🇸

Tampa, Florida, United States

CCOP - Ann Arbor Regional

🇺🇸

Ann Arbor, Michigan, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Veterans Affairs Medical Center - Milwaukee (Zablocki)

🇺🇸

Milwaukee, Wisconsin, United States

Stanford University Medical Center

🇺🇸

Stanford, California, United States

Emory University Hospital - Atlanta

🇺🇸

Atlanta, Georgia, United States

CCOP - Central Illinois

🇺🇸

Decatur, Illinois, United States

CCOP - Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Veterans Affairs Medical Center - Atlanta (Decatur)

🇺🇸

Decatur, Georgia, United States

CCOP - Evanston

🇺🇸

Evanston, Illinois, United States

Albert Einstein Comprehensive Cancer Center

🇺🇸

Bronx, New York, United States

Kaplan Cancer Center

🇺🇸

New York, New York, United States

Veterans Affairs Medical Center - Madison

🇺🇸

Madison, Wisconsin, United States

Pretoria Academic Hospital

🇿🇦

Pretoria, South Africa

CCOP - Ochsner

🇺🇸

New Orleans, Louisiana, United States

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