Deslorelin Combined With Low-Dose Add-Back Estradiol and Testosterone in Preventing Breast Cancer in Premenopausal Women Who Are at High Risk for This Disease

Biomarkers, Breast Density And Risk Reduction Perspectives In BRCA Carriers

RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Deslorelin combined with low-dose add-back estradiol and testosterone (given to replace hormones suppressed by deslorelin) may be effective in preventing breast cancer in at-risk women.

PURPOSE: This phase II trial is studying how well giving deslorelin together with estradiol and testosterone works in preventing breast cancer in premenopausal women who are at high risk for this disease.

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; brca1 Mutation Carrier; brca2 Mutation Carrier
• Intervention / Treatment: Other: laboratory biomarker analysis; Procedure: quality-of-life assessment; Biological: therapeutic estradiol; Drug: deslorelin; Drug: therapeutic testosterone; Procedure: therapeutic conventional surgery; Other: active surveillance

Detailed Description

OBJECTIVES:

I. Assess the effects on the breast of treatment with the gonadotropin-releasing hormone agonist (GnRHA)-based regimen in breast cancer (BRCA) gene mutation carriers, including correlation of changes in mammographic and magnetic resonance imaging (MRI) densities with tissue morphometrics and biomarkers.

II. Evaluate perspectives about risk reduction options and impact on quality-of-life (QOL) measures of participation in the chemopreventive protocol and in risk reduction surgery.

OUTLINE:

GROUP 1: Patients receive deslorelin, estradiol, and testosterone intranasally once daily (QD) for 6 months. Patients then undergo planned risk reduction mastectomy.

GROUP 2: Patients receive deslorelin, estradiol, and testosterone intranasally QD for 10 months. Patients then undergo continued surveillance through 10 months.

After completion of study treatment, patients are followed up every 6 months for 2 years.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010-3000
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 48 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must generally be in good health with lab values and physical examination within normal limits
• Known high risk of breast cancer due to BRCA mutation or empiric risk > 30% lifetime by the Claus model
• No evidence or history of pervious cancer, except non-melanoma skin cancer
• Premenopausal women planning risk reduction mastectomy in 6 months or more (Group 1) or continued surveillance (Group 2)
• Prior tubal ligation or willing to use a non-hormonal barrier method of contraception
• Signed the Informed Consent Form document for this study in accordance with all Federal, State and Institutional regulations
• Must be current non-smoker

Exclusion Criteria:

• GnRHA treatment within 12 months of study entry
• Nasal polyposis, atrophic rhinitis, severe allergic or vasomotor rhinitis, or sinusitis requiring current treatment or treatment for more than 3 months in the previous year
• Concurrent medications including: corticosteroids (prednisone, prednisolone, cortisone acetate, Decadron, Deltasone, hydrocortisone, Hydrocortone, Medrol), estrogens, progestins or androgens, including oral, implanted, or injected contraceptive; (At least 6 months must have elapsed since the last use of an implanted or injected contraceptive such as Norplant)
• Pregnant or breast-feeding or have been so in the last six months
• Immeasurable breast density on mammogram

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1 (planned risk reduction mastectomy); Patients receive deslorelin, estradiol, and testosterone intranasally QD for 6 months. Patients then undergo planned risk reduction mastectomy.	Other: laboratory biomarker analysis; Correlative studies; Procedure: quality-of-life assessment; Ancillary studies; Biological: therapeutic estradiol; 0.35mg/100ul per day as a nasal spray; Drug: deslorelin; 1mg/100ul per day as a nasal spray; Drug: therapeutic testosterone; 0.275mg/100ul per day as a nasal spray; Procedure: therapeutic conventional surgery; Undergo risk reduction mastectomy
Active Comparator: Group 2 (continued survaillance); Patients receive deslorelin, estradiol, and testosterone intranasally QD for 10 months. Patients then undergo continued surveillance through 10 months.	Other: laboratory biomarker analysis; Correlative studies; Procedure: quality-of-life assessment; Ancillary studies; Biological: therapeutic estradiol; 0.35mg/100ul per day as a nasal spray; Drug: deslorelin; 1mg/100ul per day as a nasal spray; Drug: therapeutic testosterone; 0.275mg/100ul per day as a nasal spray; Other: active surveillance; Undergo continued surveillance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Treatment effects and correlation of changes in morphometrics and biomarkers as assessed by mammogram and magnetic resonance image (MRI) densities on days 1 and 300	Day 300
Perspectives about risk reduction options and their impact on quality of life (QOL) as assessed by Medical Outcomes 36-item short-form version, Health Perceptions scale, and Body Image scale on days 1, 169, and 300, and then every 6 months for 2 years	2 years

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeffrey Weitzel, MD, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 11, 2004
• Primary Completion (Estimated): June 15, 2024
• Study Completion (Estimated): June 15, 2024

Study Registration Dates

• First Submitted: April 7, 2004
• First Submitted That Met QC Criteria: April 7, 2004
• First Posted (Estimated): April 8, 2004

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: breast cancer; BRCA2 mutation carrier; BRCA1 mutation carrier
• 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; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptive Agents, Female; Androgens; Estradiol; Testosterone; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Polyestradiol phosphate; Deslorelin
• Other Study ID Numbers: 02164; P30CA033572 (U.S. NIH Grant/Contract); CHNMC-IRB-02164; CDR0000355156 (Registry Identifier: NCI PDQ); NCI-2011-00975 (Registry Identifier: NCI CTRP)