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

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00186121
• Other study ID #: IRB-13429
• Secondary ID: 75597BRSMTS00011
• Status: Completed
• Phase: Phase 2
• Start date: October 2000
• Est. completion date: June 2013

Study information

• Verified date: September 2019
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 35
• Est. completion date: June 2013
• Est. primary completion date: May 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

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
• Goserelin (Zoladex)
Goserelin is a palliative treatment of advanced breast cancer in pre- and perimenopausal women

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	AstraZeneca

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall Survival (OS)	Overall survival (OS) was assessed as the median observed in the participants receiving goserelin followed by anastrozole.	up to 63 months
Secondary	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
Secondary	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