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

Phase 2

Terminated

Conditions: Breast Cancer

Interventions: Drug: Faslodex
Biological: Herceptin

Registration Number: NCT00138125

Lead Sponsor: Translational Oncology Research International

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: Female

Target Recruitment: 2

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	Herceptin	see intervention description for details
Arm I	Faslodex	see intervention description for details

Primary Outcome Measures

Name	Time	Method
Progression-free Survival	5 years	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.

Secondary Outcome Measures

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

Trial Locations

Locations (2): Jonsson Comprehensive Cancer Center at UCLA
🇺🇸
Los Angeles, California, United States
Cancer Care Associates Medical Group, Inc
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Redondo Beach, California, United States