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

National Cancer Institute (NCI)

Status and phase: Completed; Phase 2

Conditions: Breast Cancer

Treatments: Drug: cyclophosphamide; Biological: trastuzumab; Drug: tamoxifen citrate; Drug: doxorubicin hydrochloride; Drug: paclitaxel

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003992

NCI-2012-02305

E-2198

CDR0000067197 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 200 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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200 participants in 2 patient groups

Arm I

Experimental group

Description:

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.

Treatment:

Drug: paclitaxel

Drug: cyclophosphamide

Drug: tamoxifen citrate

Biological: trastuzumab

Drug: doxorubicin hydrochloride

Arm II

Experimental group

Description:

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.

Treatment:

Drug: paclitaxel

Drug: cyclophosphamide

Biological: trastuzumab

Drug: doxorubicin hydrochloride