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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003992
• Other study ID #: NCI-2012-02305
• Secondary ID: E-2198CDR0000067
• Status: Completed
• Phase: Phase 2
• First received: November 1, 1999
• Last updated: May 31, 2013
• Start date: August 1999
• Est. completion date: March 2009

Study information

• Verified date: March 2013
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: March 2009
• Est. primary completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Biological:
• trastuzumab

Drug:
• cyclophosphamide

• doxorubicin hydrochloride

• paclitaxel

• tamoxifen citrate

Locations

Country	Name	City	State
South Africa	Pretoria Academic Hospital	Pretoria
United States	Veterans Affairs Medical Center - Albany	Albany	New York
United States	CCOP - Ann Arbor Regional	Ann Arbor	Michigan
United States	Emory University Hospital - Atlanta	Atlanta	Georgia
United States	Johns Hopkins Oncology Center	Baltimore	Maryland
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	New England Medical Center Hospital	Boston	Massachusetts
United States	Albert Einstein Comprehensive Cancer Center	Bronx	New York
United States	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa
United States	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois
United States	Veterans Affairs Medical Center - Chicago (Lakeside)	Chicago	Illinois
United States	Ireland Cancer Center	Cleveland	Ohio
United States	CCOP - Central Illinois	Decatur	Illinois
United States	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia
United States	CCOP - Colorado Cancer Research Program, Inc.	Denver	Colorado
United States	Trinitas Hospital - Jersey Street Campus	Elizabeth	New Jersey
United States	CCOP - Evanston	Evanston	Illinois
United States	CCOP - Merit Care Hospital	Fargo	North Dakota
United States	Hunterdon Regional Cancer Program	Flemington	New Jersey
United States	CCOP - Northern New Jersey	Hackensack	New Jersey
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana
United States	CCOP - Kalamazoo	Kalamazoo	Michigan
United States	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin
United States	Veterans Affairs Medical Center - Madison	Madison	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin
United States	Morristown Memorial Hospital	Morristown	New Jersey
United States	Vanderbilt Cancer Center	Nashville	Tennessee
United States	CCOP - Ochsner	New Orleans	Louisiana
United States	Kaplan Cancer Center	New York	New York
United States	Veterans Affairs Medical Center - New York	New York	New York
United States	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska
United States	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California
United States	CCOP - Illinois Oncology Research Association	Peoria	Illinois
United States	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	University of Rochester Cancer Center	Rochester	New York
United States	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota
United States	Stanford University Medical Center	Stanford	California
United States	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida
United States	CCOP - Sooner State	Tulsa	Oklahoma
United States	CCOP - Carle Cancer Center	Urbana	Illinois
United States	CCOP - Wichita	Wichita	Kansas
United States	CCOP - MainLine Health	Wynnewood	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  South Africa, 

References & Publications (1)

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.