RATIONALE: Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining monoclonal antibody therapy with radiation therapy may be an effective treatment for breast cancer. PURPOSE: Phase II trial to study the effectiveness of combining trastuzumab and radiation therapy in treating women who have stage III or stage IV invasive primary cancer of the breast.

Condition	Treatment or Intervention	Phase
stage IIIB breast cancer stage IIIA breast cancer inflammatory breast cancer stage IV breast cancer recurrent breast cancer	Drug: trastuzumab	Phase II

Further Study Details: 

OBJECTIVES: I. Determine the tolerability of trastuzumab (Herceptin) and radiotherapy in women with stage III or IV invasive primary carcinoma of the breast that continues to overexpress HER2 following neoadjuvant systemic chemotherapy. II. Determine the pathologic response rate, locoregional recurrence rate, and time to locoregional recurrence in patients treated with this regimen who did not achieve clinical complete remission following neoadjuvant systemic chemotherapy.

PROTOCOL OUTLINE: Patients who received trastuzumab (Herceptin) in combination with prior neoadjuvant chemotherapy receive trastuzumab IV over 30 minutes on day 1, followed by radiotherapy on days 1-5. Patients who did not receive trastuzumab in combination with prior neoadjuvant chemotherapy receive a loading dose of trastuzumab IV over 90 minutes, followed one week later by trastuzumab IV over 30 minutes on day 1, followed by radiotherapy on days 1-5. Radiotherapy begins within 3-4 weeks after completion of neoadjuvant chemotherapy. Treatment continues weekly for 5 courses in the absence of unacceptable toxicity. Patients are followed at 3 weeks for surgical resectability, then every 3 months for 2 years, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 18-35 patients will be accrued for this study.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically proven invasive primary carcinoma of the breast by fine needle aspiration cytology, core needle biopsy, or incisional biopsy; No prior excisional biopsy
• Stage III or IV disease, including the following: Any T with N2 or N3; Inflammatory breast cancer or otherwise inoperable T4; Supraclavicular/infraclavicular adenopathy; Distant metastasis with measurable disease in the breast or lymph nodes
• Must have received neoadjuvant systemic chemotherapy with or without trastuzumab (Herceptin) within the past 4 weeks and have residual tumor that continues to overexpress HER2
• Measurable or evaluable locoregional disease after completion of neoadjuvant chemotherapy
• Synchronous bilateral primary carcinoma of the breast allowed if the more serious of the 2 carcinomas meets the above staging criteria
• Candidate for locoregional therapy consisting of radiotherapy followed by surgery
• Hormone receptor status: Not specified

--Prior/Concurrent Therapy--

• Biologic therapy: See Disease Characteristics
• Chemotherapy: See Disease Characteristics
• Endocrine therapy: Not specified
• Radiotherapy: See Disease Characteristics; No prior radiotherapy to breast or regional lymph nodes
• Surgery: See Disease Characteristics

--Patient Characteristics--

• Age: Over 18
• Sex: Female
• Menopausal status: Any status
• 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 12 g/dL
• Hepatic: Not specified
• Renal: Not specified
• Cardiovascular: Left ventricular ejection fraction normal by radionuclide ventriculography
• Other: Not pregnant or nursing; Negative pregnancy test; Fertile patients must use effective contraception

North Carolina
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States

Study chairs or principal investigators

Carolyn Sartor,  Study Chair,  UNC Lineberger Comprehensive Cancer Center   

Study ID Numbers:  CDR0000068120; UNC-9925; NCI-G00-1835
Record last reviewed:  February 2004
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006109
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08