Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy, Monoclonal Antibody Therapy, and Surgery in Treating Women With Stage II, Stage III, or Stage IV Breast Cancer

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	Not specified	NCI, Pharmaceutical / Industry	UNC-9818 NCI-G00-1836, NCT00006110

Objectives

1. Determine the cardiac and other toxicity of paclitaxel when administered with trastuzumab (Herceptin) after doxorubicin and cyclophosphamide in women with stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV breast cancer.
2. Determine whether the addition of paclitaxel with or without trastuzumab to conventional breast cancer adjuvant therapy (doxorubicin and cyclophosphamide) further decreases tumor size and the number of positive axillary nodes in these patients.
3. Determine the 5-year disease-free survival and overall survival of patients treated with these regimens.
4. Determine whether the initial pathologic response in patients receiving neoadjuvant therapy correlates with the eventual 5-year disease-free survival or overall survival.
5. Compare the number of patients eligible for breast-conserving cancer surgery after treatment with doxorubicin and cyclophosphamide vs paclitaxel and trastuzumab.
6. Correlate clinical and radiographic response rate with pathologic response rate in the primary tumor and axillary lymph nodes and determine which parameter best determines the pathologic response rate in patients treated with these regimens.

Entry Criteria

Disease Characteristics:

• Histologically confirmed stage IIB, IIIA, IIIB, IIIC, or previously untreated stage IV primary carcinoma of the breast
  • Fine needle aspiration, core needle biopsy, or incisional biopsy allowed
  • No excisional biopsy
  • Any of the following:
    • T2, N1 or T3, N0
    • Any T with N2 (including axillary lymph nodes matted to one another) or N3
    • Any T4, including inflammatory breast cancer
    • Adjuvant patients with at least 4 positive lymph nodes and HER-2 overexpressing tumor
    • Supraclavicular or infraclavicular positive lymph nodes without distant metastases
    • Distant metastases with measurable disease in breast or lymph nodes



• Synchronous bilateral primary breast cancer allowed if the more serious cancer meets entry criteria



• Measurable or evaluable disease



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• Not specified

Chemotherapy:

• Not specified

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior radiotherapy

Surgery:

• Not specified

Patient Characteristics:

Age:

• Not specified

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• WBC greater than 3,000/mm³
• Platelet count greater than 100,000/mm³
• Hemoglobin greater than 9 g/dL

Hepatic:

• Bilirubin less than 1.5 times normal

Renal:

• Creatinine less than 1.5 times normal

Cardiovascular:

• LVEF normal by resting nuclear ventriculogram

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other prior malignancies except:
  • Effectively treated squamous cell or basal cell skin cancer
  • Carcinoma in situ of the cervix that has been curatively treated by surgery alone
  • Nonbreast malignancy from which patient has been disease-free for 5 years and is at low risk of recurrence

Expected Enrollment

A total of 125 patients (100 in the neoadjuvant group and 25 in the adjuvant group) will be accrued for this study within 5 years.

Outline

Patients are assigned to receive either neoadjuvant therapy (HER-2 overexpressing and nonoverexpressing patients) or adjuvant therapy (HER-2 overexpressing patients only).

• Neoadjuvant therapy: Patients assigned to receive neoadjuvant therapy receive one of two treatment regimens.
  • Regimen I (HER-2 nonoverexpressing patients or HER-2 overexpressing patients who refuse trastuzumab (Herceptin) therapy): Patients receive doxorubicin IV and cyclophosphamide IV over 30 minutes and paclitaxel IV over 3 hours on day 1 every 3 weeks for a total of 4 courses. Patients then undergo surgery with or without adjuvant radiotherapy and/or oral tamoxifen.
  
  
  
  • Regimen II (HER-2 overexpressing patients only): Patients receive doxorubicin and cyclophosphamide as in regimen I. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90-150 minutes weekly on weeks 13-24. Patients then undergo surgery with or without adjuvant radiotherapy. Patients then receive trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.
  
  
  



• Adjuvant therapy: Patients who are assigned to receive adjuvant therapy (HER-2 overexpressing patients only) receive doxorubicin IV and cyclophosphamide IV over 30 minutes on day 1 every 3 weeks for a total of 4 courses. After completion of course 4, patients receive paclitaxel IV and trastuzumab IV over 90 minutes weekly on weeks 13-24. Patients then may undergo radiotherapy followed by trastuzumab IV over 30 minutes weekly on weeks 29-69 if they did not receive radiotherapy or on weeks 36-76 if they did receive radiotherapy.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

Trial Contact Information

Trial Lead Organizations

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Lisa Carey, MD, Protocol chair		Ph: 919-966-4431

Registry Information
Official Title		A Nonrandomized Phase II Study of Multimodality Therapy for Stage IIB, IIIA/B, or Initially Presenting Stage IV Breast Cancer with four Cycles of AC Followed by 12 Weeks of Single Agent Paciltaxel with or Without Herceptin Followed by Local Therapy Followed by Weekly Herceptin or No Additional Therapy
Trial Start Date		1998-12-01
Registered in ClinicalTrials.gov		NCT00006110
Date Submitted to PDQ		2000-07-03
Information Last Verified		2004-07-16
NCI Grant/Contract Number		P30-CA16086

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