Trastuzumab and Letrozole in Treating Postmenopausal Women With Progressive Advanced Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. Giving trastuzumab together with letrozole after disease progression may be an effective treatment for breast cancer. PURPOSE: This phase II trial is studying how well giving trastuzumab together with letrozole works in treating postmenopausal women with progressive advanced breast cancer.

Detailed Description
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OBJECTIVES: Primary Determine the efficacy of trastuzumab (Herceptin®) monotherapy followed by trastuzumab and letrozole in women with progressive advanced breast cancer that is resistant to prior treatment with a nonsteroidal aromatase inhibitor. Secondary Determine the safety profile of this regimen in these patients. Correlate HER-2-extracellular domain (ECD) levels with response to treatment in these patients. Determine the efficacy of this regimen in these patients. Correlate response and time to tumor progression with changes in serum HER-2-ECD levels in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1-3 OR once in week 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression after 9 weeks receive trastuzumab as before and oral letrozole once daily in the absence of further disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 12 weeks until disease progression and then at 6 months. PROJECTED ACCRUAL: A total of 30-40 patients will be accrued for this study.

Official Title
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Trastuzumab Monotherapy Followed By the Combination of Trastuzumab and Letrozole in Post-Menopausal Women With ER-Positive, HER-2 Positive Advanced Breast Cancer Resistant to a Nonsteroidal Aromatase Inhibitor: A Multicenter Two-Step Phase II Trial

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Trastuzumab + Letrozole


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed breast cancer Advanced disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion outside previously irradiated areas that is ≥ 20 mm OR ≥ 10 mm if the slice thickness of the CT scan or MRI is ≤ 5 mm No nonmeasurable lesions as the only site of measurable disease, including any of the following: Osteoblastic bone metastases Ascites Pleural or pericardial effusions Carcinomatous lymphangitis of the lung Progressive disease after prior treatment with a nonsteroidal aromatase inhibitor (e.g., letrozole or anastrozole) in an adjuvant or advanced disease setting HER-2 amplification ≥ 2 by fluorescence in situ hybridization No clinical symptoms or history of CNS or leptomeningeal metastases (no imaging is required) No visceral involvement with risk for organ dysfunction Hormone receptor status: Estrogen receptor- and/or progesterone receptor-positive tumor PATIENT CHARACTERISTICS: Age 18 and over Sex Female Menopausal status Postmenopausal, defined by 1 of the following: At least 55 years of age Less than 55 years of age with spontaneous cessation of menses for ≥ 1 year Less than 55 years of age with spontaneous cessation of menses within the past year, but amenorrheic with biochemical evidence of postmenopausal status Underwent prior bilateral oophorectomy Radiation or chemically induced menopause (treatment with luteinizing hormone-releasing hormone antagonists must continue during study treatment) Performance status WHO 0-1 Life expectancy Not specified Hematopoietic WBC ≥ 3,000/mm^3 Platelet count ≥ 100,000/mm^3 Hepatic AST and ALT ≤ 2 times upper limit of normal Renal Creatinine clearance > 30 mL/min Cardiovascular No uncontrolled cardiac disease, including any of the following: Unstable angina Arrhythmia Hypertension No history of congestive heart failure No myocardial infarction within the past 6 months LVEF > 50% by echocardiogram Pulmonary No severe dyspnea at rest Other No other malignancy within the past 5 years except adequately treated carcinoma in situ of the cervix or localized nonmelanoma skin cancer No psychiatric disability that would preclude study participation or giving informed consent No active autoimmune disease No uncontrolled diabetes No other serious underlying medical condition that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy No prior trastuzumab (Herceptin®) Chemotherapy Prior neoadjuvant or adjuvant chemotherapy allowed No prior palliative chemotherapy Endocrine therapy See Disease Characteristics Radiotherapy See Disease Characteristics Surgery Not specified Other More than 1 month since prior experimental drugs on another clinical trial No concurrent drugs that contraindicate study treatment No other concurrent anticancer drugs No other concurrent investigational drugs

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1-3 OR once in week 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression after 9 weeks receive trastuzumab as before and oral letrozole once daily in the absence of further disease progression or unacceptable toxicity. | Drug: Trastuzumab + Letrozole<br>* Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once in weeks 1-3 OR once in week 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients experiencing disease progression after 9 weeks receive trastuzumab as before and oral letrozole once daily in the absence of further disease progression or unacceptable toxicity.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate as assessed by CT scan or MRI every 3 months |  | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to tumor progression (TTP) every 3 months |  | 3 months | 
| Overall survival every 3 months |  | 3 months | 
| Toxicity every 3 months |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer