Clinical trial NCT03495609: Use of Recombinant hCG to Prevent Breast Cancer in BRCA1 and BRCA2 Carriers
Official title: The Use of Recombinant hCG to Prevent Breast Cancer in BRCA1 and BRCA2 Carriers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: hCG
BRCA1 Mutation
BRCA2 Mutation
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
Collaborators: name: Fox Chase Cancer Center
name: Ziekenhuis Oost-Limburg
First posted: 2018-04-12
Enrollment: 33
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 30
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Does Ovitrelle result in early prevention of breast cancer in BRCA1 and BRCA2 carriers?
timeFrame: 48 weeks
Secondary outcomes:
measure: Does Ovitrelle result in early prevention of breast cancer in BRCA1 and BRCA2 carriers?
timeFrame: 60 weeks
Other outcomes:
Locations:
city: Ghent
country: Belgium
facility: Ghent University Hospital
state: East-Flanders
Study officials:
affiliation: Fox Chase Cancer Center
name: Jose Russo, Prof.
role: PRINCIPAL_INVESTIGATOR
References: