Use of Recombinant hCG to Prevent Breast Cancer in BRCA1 and BRCA2 Carriers

The Use of Recombinant hCG to Prevent Breast Cancer in BRCA1 and BRCA2 Carriers

Specific aim: To establish the proof of principle that treatment of "high breast cancer risk" women with recombinant human chorionic gonadotropin (r-hCG) will change their breast epithelium's high risk genomic profile to one similar to that identified in women with a history of early full first term pregnancy.

Study Overview

• Status: Completed
• Conditions: BRCA1 Mutation; BRCA2 Mutation; hCG
• Intervention / Treatment: Drug: Ovitrelle

Detailed Description

This study is based on the investigators preclinical data that have demonstrated that r-hCG exerts a mammary cancer preventive effect that is mediated by the induction of gland differentiation, which results in permanent changes in the genomic signature of this organ. This exploratory study will evaluate the genomic profile of breast epithelial cells obtained from random periareolar fine needle aspiration (RPFNA) specimens performed in high risk women treated for 90 days (an extra 4 weeks in a subgroup) with r-hCG. This knowledge will serve as the basis for establishing a novel genomic biomarker that will serve as a surrogate endpoint in future preventive clinical trials.

The objective of the proposed study is to characterize the genomic profile of breast epithelial cells obtained from 35 asymptomatic high breast cancer risk nulliparous premenopausal women carriers of BRCA1 and BRCA2 deleterious mutations. Gene expression measurements and benign breast tissue specimens will be obtained at baseline (time 0), after treatment with r-hCG at 90 days (time 1), at 270 days from baseline (time 2) and (in a subgroup) at 60 weeks (+/- 4 weeks).

The primary objective of the study is to compare the gene expression profiles of these women across the three (or four) time points and identify differentially expressed genes. The investigator is interested in comparing the expression profiles between all pairs of time points as well as across time. The comparison of profiles before and after treatment with r-hCG, both at 90 and 270 days are of particular interest. The women will receive 3x/week injections of 250 microgram r-hCG for a total of 12 weeks (an extra 4 weeks in a subgroup). Core Needle Biopsies specimens will be primarily utilized for analysis of genomic expression by cDNA microarray. In addition, a series of surrogate intermediate markers such as cytomorphologic evaluation and cell proliferation index will be analyzed.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • East-Flanders
    • Ghent, East-Flanders, Belgium, 9000
      • Ghent University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 30 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• premenopausal women
• BRCA1 carrier

Exclusion Criteria:

• History of allergic reaction to compounds of similar chemical or biologic composition to hCG
• receiving medication that could interfere with the study protocol objectives (hormonal contraceptives, androgens, prednisone, thyroid hormones, insulin)
• previous treatment with follicle stimulating hormone for assisted reproduction
• uncontrolled intercurrent illness
• Heart disease
• Severe cognitive decline
• Psychiatric desease
• HIV positive
• Hepatitis B or C infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Ovitrelle	Drug: Ovitrelle; Ovitrelle will be injected in 35 asymptomatic women with BRCA1 or BRCA2 mutation during 90 days (an extra 4 weeks in a subgroup). The gene expression of the breast epithelial cells will be characterized and compared to the gene expression of the breast epithelial cells before ovitrelle injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Does Ovitrelle result in early prevention of breast cancer in BRCA1 and BRCA2 carriers?	The investigators are expecting that r-hCG is inducing genomic signature of protection in the breast. Participants will receive a subcutaneous injection of recombinant hCG three times a week for 12 (or 16) weeks. Normal breast tissue specimens will be collected by Spirotome at the beginning of treatment (day 0), at the end of treatment (week 13) and at 36 weeks. The specimens will be primarily utilized for analysis of genomic expression by cDNA microarray, RNA sequencing and epigenomic studies. In addition, a series of surrogate intermediate markers such as cytomorphologic evaluation and cell proliferation index will be analyzed. The primary objective is to compare the gene expression, and epigenomic profiles of sampled breast epithelial cells across the three time points and identify differentially expressed or silenced genes.	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Does Ovitrelle result in early prevention of breast cancer in BRCA1 and BRCA2 carriers?	The investigators are expecting that r-hCG is inducing genomic signature of protection in the breast. Participants will receive a subcutaneous injection of recombinant hCG three times a week for 12 (or 16) weeks. Normal breast tissue specimens will be collected by Spirotome at the beginning of treatment (day 0), at the end of treatment (week 13) and at 36 weeks. The specimens will be primarily utilized for analysis of genomic expression by cDNA microarray, RNA sequencing and epigenomic studies. In addition, a series of surrogate intermediate markers such as cytomorphologic evaluation and cell proliferation index will be analyzed. The primary objective is to compare the gene expression, and epigenomic profiles of sampled breast epithelial cells across the three time points and identify differentially expressed or silenced genes.	60 weeks

Collaborators and Investigators

• Sponsor: University Hospital, Ghent
• Collaborators: Fox Chase Cancer Center; Ziekenhuis Oost-Limburg
• Investigators: Principal Investigator: Jose Russo, Prof., Fox Chase Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2016
• Primary Completion (Actual): December 18, 2018
• Study Completion (Actual): December 18, 2018

Study Registration Dates

• First Submitted: January 23, 2018
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (Actual): April 12, 2018

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 1, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Chorionic Gonadotropin
• Other Study ID Numbers: 2015-001720-36

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No