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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003992

Collaborator

(none)

200

Enrollment

Locations

Arms

115

Duration (Months)

4.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer	Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel Drug: tamoxifen citrate	Phase 2

Detailed Description

OBJECTIVES:

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.
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 Design

Study Type:

Interventional

Actual Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 1999

Actual Primary Completion Date :

Jan 1, 2007

Actual Study Completion Date :

Mar 1, 2009

Arms and Interventions

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.	Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel 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.	Biological: trastuzumab Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: paclitaxel

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.

Biological: trastuzumab

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: paclitaxel

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.

Biological: trastuzumab

Drug: cyclophosphamide

Drug: doxorubicin hydrochloride

Drug: paclitaxel

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Palo Alto	Palo Alto	California	United States	94304
2	Stanford University Medical Center	Stanford	California	United States	94305-5408
3	CCOP - Colorado Cancer Research Program, Inc.	Denver	Colorado	United States	80209-5031
4	H. Lee Moffitt Cancer Center and Research Institute	Tampa	Florida	United States	33612
5	Emory University Hospital - Atlanta	Atlanta	Georgia	United States	30322
6	Veterans Affairs Medical Center - Atlanta (Decatur)	Decatur	Georgia	United States	30033
7	Robert H. Lurie Comprehensive Cancer Center, Northwestern University	Chicago	Illinois	United States	60611
8	Veterans Affairs Medical Center - Chicago (Lakeside)	Chicago	Illinois	United States	60611
9	CCOP - Central Illinois	Decatur	Illinois	United States	62526
10	CCOP - Evanston	Evanston	Illinois	United States	60201
11	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61602
12	CCOP - Carle Cancer Center	Urbana	Illinois	United States	61801
13	Veterans Affairs Medical Center - Indianapolis (Roudebush)	Indianapolis	Indiana	United States	46202
14	CCOP - Cedar Rapids Oncology Project	Cedar Rapids	Iowa	United States	52403-1206
15	CCOP - Wichita	Wichita	Kansas	United States	67214-3882
16	CCOP - Ochsner	New Orleans	Louisiana	United States	70121
17	Johns Hopkins Oncology Center	Baltimore	Maryland	United States	21231
18	New England Medical Center Hospital	Boston	Massachusetts	United States	02111
19	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
20	CCOP - Ann Arbor Regional	Ann Arbor	Michigan	United States	48106
21	CCOP - Kalamazoo	Kalamazoo	Michigan	United States	49007-3731
22	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
23	CCOP - Metro-Minnesota	Saint Louis Park	Minnesota	United States	55416
24	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68131
25	Trinitas Hospital - Jersey Street Campus	Elizabeth	New Jersey	United States	07201
26	Hunterdon Regional Cancer Program	Flemington	New Jersey	United States	08822
27	CCOP - Northern New Jersey	Hackensack	New Jersey	United States	07601
28	Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
29	Morristown Memorial Hospital	Morristown	New Jersey	United States	07962-1956
30	Veterans Affairs Medical Center - Albany	Albany	New York	United States	12208
31	Albert Einstein Comprehensive Cancer Center	Bronx	New York	United States	10461
32	Veterans Affairs Medical Center - New York	New York	New York	United States	10010
33	Kaplan Cancer Center	New York	New York	United States	10016
34	University of Rochester Cancer Center	Rochester	New York	United States	14642
35	CCOP - Merit Care Hospital	Fargo	North Dakota	United States	58122
36	Ireland Cancer Center	Cleveland	Ohio	United States	44106-5065
37	CCOP - Sooner State	Tulsa	Oklahoma	United States	74136
38	University of Pennsylvania Cancer Center	Philadelphia	Pennsylvania	United States	19104
39	CCOP - MainLine Health	Wynnewood	Pennsylvania	United States	19096
40	Vanderbilt Cancer Center	Nashville	Tennessee	United States	37232-6838
41	Veterans Affairs Medical Center - Madison	Madison	Wisconsin	United States	53705
42	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792
43	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226
44	Veterans Affairs Medical Center - Milwaukee (Zablocki)	Milwaukee	Wisconsin	United States	53295
45	Pretoria Academic Hospital	Pretoria		South Africa	0001