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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Anastrozole (Arimidex); Drug: Goserelin (Zoladex)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

INCLUSION CRITERIA

• Histologically-confirmed, bi-dimensionally measurable, recurrent or metastatic carcinoma of the breast that is progressive

• Premenopausal, defined as any of:

  1. Last menstrual period within 3 months, or
  2. Post-hysterectomy without bilateral oophorectomy and with follicle-stimulating hormone (FSH) in the premenopausal range, or,
  3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Anastrozole + Goserelin; 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); 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; Other Names: Arimidex; Drug: Goserelin (Zoladex); Goserelin is a palliative treatment of advanced breast cancer in pre- and perimenopausal women; Other Names: Zoladex

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Melinda Telli, MD, Stanford University

Publications and helpful links

General Publications

• Carlson RW, Theriault R, Schurman CM, Rivera E, Chung CT, Phan SC, Arun B, Dice K, Chiv VY, Green M, Valero V. Phase II trial of anastrozole plus goserelin in the treatment of hormone receptor-positive, metastatic carcinoma of the breast in premenopausal women. J Clin Oncol. 2010 Sep 1;28(25):3917-21. doi: 10.1200/JCO.2009.24.9565. Epub 2010 Aug 2.

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Actual): May 1, 2013
• Study Completion (Actual): June 1, 2013

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Actual): October 7, 2019
• Last Update Submitted That Met QC Criteria: September 23, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Goserelin; Anastrozole
• Other Study ID Numbers: IRB-13429; 75597 (Other Identifier: Stanford IRB alternate); BRSMTS0001 (Other Identifier: OnCore); 1033VS0012 (Other Identifier: alternate)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No