Clinical trial NCT00700778: Recombinant Human Chorionic Gonadotropin in Preventing Breast Cancer in Premenopausal Women With BRCA1 Mutations
Official title: Genomic Markers of Breast Cancer Prevention Induced by HCG in Women at High Risk
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: BRCA1 Mutation
Breast Cancer
Keywords: breast cancer
BRCA1 mutation carrier
Lead sponsor: Fox Chase Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-06-19
Enrollment: 2
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming. The use of recombinant human chorionic gonadotropin may prevent breast cancer in premenopausal women with BRCA1 mutations.

PURPOSE: This clinical trial is studying recombinant human chorionic gonadotropin in preventing breast cancer in premenopausal women with BRCA1 mutations.

Detailed description: OBJECTIVES:

Primary

* Determine whether the genomic profiles of breast epithelial cells of high-breast cancer-risk women, as defined by their positive BRCA1 status and nulliparous condition, express a signature indicative of high-risk.

Secondary

* Determine whether women identified to express a "high-breast cancer-risk" signature will revert it to a "low-risk" signature after a 90-day treatment with r-hCG, which should have induced breast differentiation and genomic changes that would serve as biomarkers indicative of decreased breast cancer risk.

OUTLINE: Patients receive recombinant human chorionic gonadotropin subcutaneously three times weekly. Treatment continues weekly for 90 days in the absence of unacceptable toxicity.

Benign breast tissue specimens are collected by core needle biopsy at baseline, day 90, and day 270. Tissue samples are analyzed by cytopathology for epithelial normality, Ki67 immunohistochemical staining for cell proliferation, cDNA microarray for gene expression, and serum studies for hormone levels and biomarker determinations.

After completion of study treatment, patients are followed for 24 weeks.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Asymptomatic women who have a deleterious mutation on the BRCA1 gene
* Normal, no complaints, no evidence of disease
* Nulliparous, never pregnant (G0P0)
* No previous diagnosis of breast or ovarian cancer
* No known brain metastases
* Hormone receptor status not specified

PATIENT CHARACTERISTICS:

* ECOG performance status (PS) 0-1 OR Karnofsky PS 90-100%
* Premenopausal with normal menstrual cycles and intact ovaries
* Normal ovarian size report from pelvic ultrasound
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective barrier contraception
* No history of allergic reactions attributed to compounds of similar chemical or biologic composition to human chorionic gonadotropin preparations or one of its excipients
* No uncontrolled intercurrent illness including any of the following:

  * Ovarian enlargement of undetermined origin
  * Ovarian cysts \> 2 cm
  * Microcystic ovaries, which might predispose to the development of ovarian hyperstimulation syndrome
  * History of prior cancer other than non-melanoma skin cancer
  * Ongoing or active infection
  * Symptomatic congestive heart failure
  * Unstable angina pectoris
  * Cardiac arrhythmia
  * Severe cognitive deficit or psychiatric illness/social situations that would make her unable to give informed consent or would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

* At least 6 weeks since prior and no concurrent oral contraceptives or hormone-replacement therapy
* No concurrent tamoxifen for chemoprevention
* No concurrent participation in another chemopreventive trial for breast cancer
* No concurrent medication that could interfere with this study including any of the following:

  * Hormonal contraceptives
  * Androgens
  * Prednisone
  * Thyroid hormones
  * Insulin
* No other concurrent investigational agents
* No recent treatment with follicle-stimulating hormone for assisted reproduction
* No HIV-positive patients on concurrent combination antiretroviral therapy

Primary outcomes:
measure: Measurement of Gene Expression in Breast Epithelial Cells Obtained for Asymptomatic High Breast Cancer Risk Nulliparous Premenopausal Women at Baseline, After Treatment With r-hCG at 90 Days, and at 270 Days From Baseline
timeFrame: 90 days and 270 days from baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center - Philadelphia
state: Pennsylvania
city: Vienna
country: Austria
facility: Universitaetsklinik fuer Frauenheilkunde
Study officials:
affiliation: Fox Chase Cancer Center
name: Jose Russo, MD, FCAP
role: PRINCIPAL_INVESTIGATOR
References: