Clinical trial NCT00003992: Chemotherapy Plus Monoclonal Antibody Therapy in Treating Women With Stage II or Stage IIIA Breast Cancer That Overexpresses HER2
Official title: Pilot Trial of Paclitaxel-Herceptin Adjuvant Therapy for Early Stage Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage II breast cancer
stage IIIA breast cancer
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2004-06-09
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

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