Estradiol Suppression for the Treatment of Metastatic Breast Cancer in Premenopausal Women

Study Overview
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Brief Summary
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To evaluate the antitumor activity, toxicity, and effectiveness of the combination of goserelin (Zoladex) and anastrozole (Arimidex) in the treatment of premenopausal women with hormone receptor positive metastatic carcinoma of the breast.

Detailed Description
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Pre-menopausal women with estrogen and/or progesterone receptor positive, metastatic or recurrent breast cancer were enrolled and treated with goserelin (Zoladex) monthly and began anastrozole (Arimidex) daily for 21 days following the first injection of goserelin. Participants continued on treatment until disease progression or unacceptable toxicity.

Official Title
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A Phase II Trial of Arimidex Plus Zoladex in the Treatment of Hormone Receptor Positive, Metastatic Carcinoma of the Breast in Premenopausal Women

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Anastrozole (Arimidex)
* Drug: Goserelin (Zoladex)


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Histologically-confirmed, bi-dimensionally measurable, recurrent or metastatic carcinoma of the breast that is progressive Premenopausal, defined as any of: Last menstrual period within 3 months, or Post-hysterectomy without bilateral oophorectomy and with follicle-stimulating hormone (FSH) in the premenopausal range, or, If tamoxifen administered within the past 3 months, plasma estradiol must be in the premenopausal range Either positive estrogen and/or progesterone receptor determination by Immunohistochemistry (IHC) or competitive binding assay on metastatic disease, or if not performed on their metastatic disease a positive result on their primary breast cancer specimen. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Granulocytes > 1500/mm^3 Platelets > 100,000/mm^3 Serum glutamic oxaloacetic transaminase (SGOT) < 2.5 x upper limit of normal Total bilirubin < 1.5 mg/dL May have received irradiation to bony sites of disease for pain control or for prevention of fracture. The irradiated site(s) will NOT be evaluable for disease response. Must be using effective contraception or not be of childbearing potential Signed written informed consent INCLUSION CRITERIA Active, unresolved infection Active malignancy other than breast cancer, in situ carcinoma of the cervix, or non-melanomatous skin cancers in the past 5 years Prior treatment with an aromatase inhibitor or inactivator Prior treatment with an luteinizing hormone-releasing hormone (LH/RH) agonist/antagonist Adjuvant chemotherapy within 6 months of study entry. Received chemotherapy or hormonal therapy in the 3 weeks prior to enrollment Central nervous system metastasis Lymphangitic pulmonary metastasis Pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Anastrozole + Goserelin<br>Participants received goserelin 3.6 mg subcutaneously monthly. Beginning on Day 22 after the first dose of goserelin, participants began taking anastrozole 1 mg orally daily. No dose attenuation or escalation was allowed for either goserelin or anastrozole. | Drug: Anastrozole (Arimidex)<br>* Anastrozole is a prescription hormonal treatment that helps fight breast cancer by lowering the amount of estrogen in the body. It is a non-steroidal aromatase inhibitor, which significantly lowers serum estradiol (estrogen) concentrations, without interfering with the formation of adrenal corticosteroids or aldosterone<br>* Other names: Arimidex;Drug: Goserelin (Zoladex)<br>* Goserelin is a palliative treatment of advanced breast cancer in pre- and perimenopausal women<br>* Other names: Zoladex;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR was determined as the sum of the Complete Response (CR) rate + Partial Response (PR) rates. CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. All measurements by ruler or calipers. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Benefit Rate | The overall clinical benefit rate of goserelin followed by anastrozole was evaluated, as determined as the sum of the Complete Response (CR) rate + Partial Response (PR) rate + Stable Disease (SD) rate. CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. SD = No significant change in measurable or evaluable disease for at least 4 weeks. All measurements by ruler or calipers. | 6 months | 
| Response Rates | The numbers of participants with metastatic breast cancer experiencing Complete Response (CR); Partial Response (PR); or Stable Disease (SD) after treatment with goserelin followed by anastrozole are reported. CR = Complete disappearance of all clinically- or pathologically-detectable malignant disease for at least 4 weeks. PR = ≥ 50% decrease in tumor size for at least 4 weeks, without any new lesion or any ≥ 25% increase in size of any lesion. SD = No significant change in measurable or evaluable disease for at least 4 weeks. All measurements by ruler or calipers. | 6 months | 
| Time-to-Progression (TTP) | Time-to-progression (TTP) was assessed as the median observed in the participant group. Progression of disease was considered, per protocol, to be ≤ 25% increase in the area of any malignant lesion greater than 2 square cm, or ≤ 25% increase in the sum of the products of the longest perpendicular diameters of individual lesions in a given organ, when compared to baseline values or after therapeutic response. | up to 63 months | 
| Overall Survival (OS) | Overall survival (OS) was assessed as the median observed in the participants receiving goserelin followed by anastrozole. | up to 63 months | 
| Estradiol Suppression | Plasma estradiol determinations were performed at baseline, 1 month, 3 months, and 6 months using the Coat-A-Count Estradiol competitive binding assay system, which has a calibrated range for estradiol of 20 to 3,600 pg/mL with an analytical sensitivity of 10 pg/mL. | 6 months | 
| Serious Adverse Events | The toxicity of the treatment regimen of goserelin followed by anastrozole is estimated by the rate of Serious Adverse Events (SAEs) that occurred during the course of the study. | 6 months |