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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03495609
Recruitment Status : Completed
First Posted : April 12, 2018
Last Update Posted : August 28, 2019
Sponsor:
Collaborators:
Fox Chase Cancer Center
Ziekenhuis Oost-Limburg
Information provided by (Responsible Party):
Steven Weyers, MD, PhD, University Hospital, Ghent

Tracking Information
First Submitted Date  ICMJE January 23, 2018
First Posted Date  ICMJE April 12, 2018
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE February 17, 2016
Actual Primary Completion Date December 18, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 4, 2018)		 Does Ovitrelle result in early prevention of breast cancer in BRCA1 and BRCA2 carriers? [ Time Frame: 48 weeks ]
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 4, 2018)		 Does Ovitrelle result in early prevention of breast cancer in BRCA1 and BRCA2 carriers? [ Time Frame: 60 weeks ]
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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Use of Recombinant hCG to Prevent Breast Cancer in BRCA1 and BRCA2 Carriers
Official Title  ICMJE The Use of Recombinant hCG to Prevent Breast Cancer in BRCA1 and BRCA2 Carriers
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE
  • hCG
  • BRCA1 Mutation
  • BRCA2 Mutation
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Ovitrelle
Intervention: Drug: Ovitrelle
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 26, 2019)		 33
Original Estimated Enrollment  ICMJE
 (submitted: April 4, 2018)		 35
Actual Study Completion Date  ICMJE December 18, 2018
Actual Primary Completion Date December 18, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: Only females who are BRCA1 or BRCA2 carriers and who are premenopausal will be included
Ages  ICMJE 18 Years to 30 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03495609
Other Study ID Numbers  ICMJE 2015-001720-36
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Steven Weyers, MD, PhD, University Hospital, Ghent
Original Responsible Party Vrouwenkliniek, University Hospital, Ghent, prof. dr. Herman Depypere
Current Study Sponsor  ICMJE University Hospital, Ghent
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Fox Chase Cancer Center
  • Ziekenhuis Oost-Limburg
Investigators  ICMJE
Principal Investigator: Jose Russo, Prof. Fox Chase Cancer Center
PRS Account University Hospital, Ghent
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP