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

NCT ID: NCT00003992

Last Updated: 2013-06-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

200 participants

Study Classification

INTERVENTIONAL

Study Start Date

1999-08-31

Study Completion Date

2009-03-31

Brief Summary

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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

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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.

Conditions

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Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

trastuzumab

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

paclitaxel

Intervention Type DRUG

tamoxifen citrate

Intervention Type DRUG

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.

Group Type EXPERIMENTAL

trastuzumab

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

paclitaxel

Intervention Type DRUG

Interventions

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trastuzumab

Intervention Type BIOLOGICAL

cyclophosphamide

Intervention Type DRUG

doxorubicin hydrochloride

Intervention Type DRUG

paclitaxel

Intervention Type DRUG

tamoxifen citrate

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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George W. Sledge, MD

Role: STUDY_CHAIR

Indiana University Melvin and Bren Simon Cancer Center

Locations

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Veterans Affairs Medical Center - Palo Alto

Palo Alto, California, United States

Site Status

Stanford University Medical Center

Stanford, California, United States

Site Status

CCOP - Colorado Cancer Research Program, Inc.

Denver, Colorado, United States

Site Status

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Site Status

Emory University Hospital - Atlanta

Atlanta, Georgia, United States

Site Status

Veterans Affairs Medical Center - Atlanta (Decatur)

Decatur, Georgia, United States

Site Status

Robert H. Lurie Comprehensive Cancer Center, Northwestern University

Chicago, Illinois, United States

Site Status

Veterans Affairs Medical Center - Chicago (Lakeside)

Chicago, Illinois, United States

Site Status

CCOP - Central Illinois

Decatur, Illinois, United States

Site Status

CCOP - Evanston

Evanston, Illinois, United States

Site Status

CCOP - Illinois Oncology Research Association

Peoria, Illinois, United States

Site Status

CCOP - Carle Cancer Center

Urbana, Illinois, United States

Site Status

Veterans Affairs Medical Center - Indianapolis (Roudebush)

Indianapolis, Indiana, United States

Site Status

CCOP - Cedar Rapids Oncology Project

Cedar Rapids, Iowa, United States

Site Status

CCOP - Wichita

Wichita, Kansas, United States

Site Status

CCOP - Ochsner

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Oncology Center

Baltimore, Maryland, United States

Site Status

New England Medical Center Hospital

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

CCOP - Ann Arbor Regional

Ann Arbor, Michigan, United States

Site Status

CCOP - Kalamazoo

Kalamazoo, Michigan, United States

Site Status

Mayo Clinic Cancer Center

Rochester, Minnesota, United States

Site Status

CCOP - Metro-Minnesota

Saint Louis Park, Minnesota, United States

Site Status

CCOP - Missouri Valley Cancer Consortium

Omaha, Nebraska, United States

Site Status

Trinitas Hospital - Jersey Street Campus

Elizabeth, New Jersey, United States

Site Status

Hunterdon Regional Cancer Program

Flemington, New Jersey, United States

Site Status

CCOP - Northern New Jersey

Hackensack, New Jersey, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Morristown Memorial Hospital

Morristown, New Jersey, United States

Site Status

Veterans Affairs Medical Center - Albany

Albany, New York, United States

Site Status

Veterans Affairs Medical Center - New York

New York, New York, United States

Site Status

Kaplan Cancer Center

New York, New York, United States

Site Status

University of Rochester Cancer Center

Rochester, New York, United States

Site Status

Albert Einstein Comprehensive Cancer Center

The Bronx, New York, United States

Site Status

CCOP - Merit Care Hospital

Fargo, North Dakota, United States

Site Status

Ireland Cancer Center

Cleveland, Ohio, United States

Site Status

CCOP - Sooner State

Tulsa, Oklahoma, United States

Site Status

University of Pennsylvania Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

CCOP - MainLine Health

Wynnewood, Pennsylvania, United States

Site Status

Vanderbilt Cancer Center

Nashville, Tennessee, United States

Site Status

Veterans Affairs Medical Center - Madison

Madison, Wisconsin, United States

Site Status

University of Wisconsin Comprehensive Cancer Center

Madison, Wisconsin, United States

Site Status

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Veterans Affairs Medical Center - Milwaukee (Zablocki)

Milwaukee, Wisconsin, United States

Site Status

Pretoria Academic Hospital

Pretoria, , South Africa

Site Status

Countries

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United States South Africa

References

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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.

Reference Type RESULT

Other Identifiers

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E-2198

Identifier Type: -

Identifier Source: secondary_id

CDR0000067197

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02305

Identifier Type: -

Identifier Source: org_study_id

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