Clinical trial NCT01769625: Changes in Biomarkers Using Prostaglandin Inhibitors
Official title: Prostaglandin Inhibition to Prevent Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Biomarker Change Linked to Breast Cancer
Keywords: breast
high risk women
biomarkers
vitamin D
Lead sponsor: Hartford Hospital
Sponsor class: OTHER
Collaborators: name: Susan G. Komen Breast Cancer Foundation
First posted: 2013-01-16
Enrollment: 31
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This is a biomarker study with the goal of measuring changes in proteins and gene methylation. This study is not intended for use in diagnosing, mitigating, treating, curing, or preventing disease.

The purpose of this study is to determine if Vitamin D (cholecalciferol) alone and in combination with celecoxib (Celebrex, a non-steroidal anti-inflammatory drug, or NSAID), act together to decrease breast cancer risk by their effect on certain biological indicators (biomarkers) of breast cancer risk (called PGE2, COX-2, and 15-PGDH) and cell changes in the breast.

Detailed description: This is a biomarker study with the goal of measuring changes in protein and rna expression. This study is not intended for use in diagnosing, mitigating, treating, curing, or preventing disease.

66 women at normal risk for developing breast cancer will be recruited and enrolled. 22 women will be randomized into each arm, with anticipation of 2 women in each group will not be evaluable, leaving 20 in each group for evaluation.

A combination of vitamin D and celecoxib act synergistically to decrease breast cancer risk by decreasing cell proliferation in the mammary epithelium through their action on prostaglandin synthesis and metabolism.

Specific Aims:

-Evaluate vitamin D metabolism, through the measurement of CYP24 in the breast.

2-Evaluate breast specific levels of vitamin D and celecoxib, and assess if the levels of these compounds correlate with response to markers which influence prostaglandin synthesis and metabolism. Additionally, in women without active breast cancer , we will determine the effect of vitamin D, with or without celecoxib, on 1) PG synthesis and metabolism, through the measurement of PGE2, COX-2 and 15-PGDH in the breast, 2) proliferative activity in the breast,, and 3) circulating levels of vitamin D and celecoxib, to determine if levels of these compounds correlate with response to markers of PG production, metabolism, or cell proliferation.

Eligibility criteria: Inclusion Criteria:

* Woman \>18 years old
* Healthy women who are at normal risk for developing breast cancer
* ECOG Performance Status score 0-1
* Premenopausal women must not be pregnant

Exclusion Criteria:

* History of bilateral mastectomy, or bilateral breast irradiation
* Significant medical or psychiatric problems making the participant a poor candiate
* Evidence of excess use of narcotics or drug dependency
* Have been pregnant and lactating in the past 2 years
* Significant history of peptic ulcer disease or upper gastrointestinal bleeding
* History of severe congestive heart failure that requires hospitalization or intervention
* History of asthma requiring medication for treatment
* Allergy to sulfonamides or NSAID medications
* History of myocardial infarction or stroke
* Currently on Coumadin
* Currently on Tamoxifen (nolvadex),Evista (raloxifene), Femara (letrozole), Arimidex (anastrozole), or Aromasin (exemestane)
* Undergone prior subaeolar breast surgery

Primary outcomes:
measure: PG synthesis and metabolism, through the measurement of PGE2, COX-2 and 15-PGDH in the breast
timeFrame: approximately 30 days
Secondary outcomes:
measure: proliferative activity in the breast and circulating levels of vitamin D and celecoxib, to determine if levels of these compounds correlate with response to markers of PG production, metabolism, or cell proliferation.
timeFrame: approximately 30 days
Other outcomes:
Locations:
city: Grand Forks
country: United States
facility: University of North Dakota
state: North Dakota
Study officials:
affiliation: University of North Dakota
name: Edward R. Sauter, MD, PhD, M.H.A
role: PRINCIPAL_INVESTIGATOR
References: