Fulvestrant and/or Trastuzumab as First-Line Therapy in Treating Postmenopausal Women With Stage IV Breast Cancer

Study Overview
=================
Brief Summary
-----------------
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using fulvestrant may fight breast cancer by lowering the amount of estrogen the body makes. 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. It is not yet known whether giving fulvestrant together with trastuzumab is more effective than giving fulvestrant or trastuzumab alone in treating breast cancer. PURPOSE: This randomized phase II trial is studying how well fulvestrant and/or trastuzumab works as first-line therapy in treating postmenopausal women with stage IV breast cancer.

Detailed Description
-----------------
OBJECTIVES: Primary Compare the overall objective response rate in postmenopausal women with estrogen receptor (ER)- and/or progesterone receptor (PR)-positive, HER2/neu-overexpressing stage IV breast cancer treated with first-line therapy comprising fulvestrant and/or trastuzumab (Herceptin®). Secondary Compare the duration of response in patients treated with these regimens. Compare overall survival of patients treated with these regimens. Compare the antitumor activity of these regimens, in terms of time to disease progression, in these patients. Compare the clinical benefit of these regimens in these patients. Determine the safety and toxicity of these regimens in these patients. Correlate HER2/neu expression and ER and/or PR expression with response in patients treated with these regimens. OUTLINE: This is a randomized, controlled, open-label, multicenter study. Patients are stratified according to prior adjuvant endocrine therapy (yes vs no). Patients are randomized to 1 of 3 treatment arms. Arm I: Patients receive fulvestrant intramuscularly on days 1 and 15 of course 1 and then on day 1 only in all subsequent courses. Arm II: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, 15, and 22. Arm III: Patients receive fulvestrant as in arm I in combination with trastuzumab as in arm II. In all arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed every 8 weeks. PROJECTED ACCRUAL: A total of 120 patients (40 per treatment arm) will be accrued for this study.

Official Title
-----------------
Phase II Randomized Trial of Faslodex and Herceptin, Alone and Combined, in the First - Line Treatment of Hormone Receptor-Positive, HER-2/Neu-Overexpressing Metastatic Breast Cancer

Conditions
-----------------
Breast Cancer

Intervention / Treatment
-----------------
* Drug: Faslodex
* Biological: Herceptin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female patient, postmenopausal, defined as a woman fulfilling any one of the following criteria: Age 60 years or older Age 45 years or older with amenorrhea for > 12 months with an intact uterus Follicle-stimulating hormone and estradiol levels within post-menopausal range Having undergone a bilateral oophorectomy Histologically or cytologically proven adenocarcinoma of the breast Subjects must have archived rumor tissue available to compare the clinical response with tumor expression of biomarkers, such as HER-2, ER and PR; archived tissue will be used to confirm HER-2, ER and PR status, but results will not be used to determine subject eligibility for the study HER2-positive disease ER-positive and/or PR-positive disease ECOG performance status 0-2 Life expectancy > 24 weeks Left ventricular ejection fraction > lower limit of normal No prior chemotherapy, endocrine therapy, Herceptin, or other biologic or investigational therapy for metastatic breast cancer No more than two prior endocrine agents in the adjuvant setting as single- or sequential-therapy is permitted, but no prior Faslodex therapy is permitted. A 1-month treatment-free period is required prior to receiving the first dose of trial treatments Prior adjuvant chemotherapy is permitted Prior adjuvant Herceptin permitted At least 1 month since prior surgery, radiotherapy, or endocrine therapy, with complete recovery from the effects of these interventions Patients must have ended any hormone replacement therapy at least 1 month prior to receiving the first dose of trial therapy Patients treated with bisphosphonates may enroll, with heir bone lesions only assessable for disease progression Patient is accessible and willing to comply with treatment and follow-up Patient is willing to provide written informed consent prior to the performance of any study-related procedures Required laboratory values: Absolute neutrophil count > 1.5 x 10^9/L Hemoglobin > 10g/dL Platelet count > 100 x 10^9/L Creatinine < 2.0 mg/dL Total bilirubin < 1.5 x upper limit of normal AST and ALT < 2.5 x ULN Exclusion Criteria: Prior chemotherapy, hormonal therapy, Herceptin or other investigational therapy for metastatic breast cancer Prior treatment with Faslodex Concurrent therapy with any other non-protocol anti-cancer therapy Current or prior history of brain metastases History of any other malignancy within the past 5 years, with the exception of non-melanoma skin cancer or carcinoma-in-situ of the cervix Clinically significant cardiovascular disease, New York Heart Association Class II or greater congestive heart failure, or serious cardiac arrhythmia requiring medication Prior exposure of > 360 mg/m2 doxorubicin or liposomal doxorubicin, > 120 mg/m2 mitoxantrone, > 90 mg/m2 idarubicin, or > 720 mg/m2 epirubicin Active, uncontrolled infection requiring parenteral antimicrobials The presence of any other medical or psychiatric disorder that, in the opinion of the treating physician, would contraindicate the use of the drugs in this protocol or place the subject at undue risk for treatment complications Inability to comply with the study protocol or follow-up procedures Known hypersensitivity to any of the drugs used in this protocol or to active or inactive excipients of Faslodex History of bleeding diasthesis Long-term anticoagulant therapy other than anti-platelet therapy, such as with warfarin

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>see intervention description for details | Drug: Faslodex<br>* Administered IM at 500 mg on day 1 of cycle 1, followed by 500 mg on day 15 of cycle 1, then 500 mg on day 1 of each cycle thereafter.<br>Biological: Herceptin<br>* Given at 4 mg/kg IV on day 1 (cycle 1) then 2mg/kg IV weekly<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Of the two treated patients on this trial, the records show that one patient who received Herceptin only completed 3 cycles of therapy, while the second patient who received Herceptin in combination with Faslodex completed 9 cycles of therapy. The last survival data collected from October to November 2008 showed that these two participants were alive at that time. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Objective Response Rate | Two patients were treated on a truncated trial. Not enough data was generated for any analysis. | 5 years | 
| Time to Tumor Progression | Two patients were treated on a truncated trial. Not enough data was generated for any analysis. | 5 years | 
| Duration of Response | Two patients were treated on a truncated trial. Not enough data was generated for any analysis. | 5 years | 
| Overall Survival | Two patients were treated on a truncated trial. Not enough data was generated for any analysis. | 5 years | 
| Clinical Benefit (CR + PR + SD > 6 Months) | Two patients were treated on a truncated trial. Not enough data was generated for any analysis. | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stage IV breast cancer, recurrent breast cancer