Changes in Biomarkers Using Prostaglandin Inhibitors

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Susan G. Komen Breast Cancer Foundation
Information provided by (Responsible Party):
Edward Sauter, The University of Texas Health Science Center at Tyler
ClinicalTrials.gov Identifier:
NCT01769625
First received: January 14, 2013
Last updated: May 11, 2016
Last verified: May 2016
  Purpose

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.


Condition Intervention Phase
Biomarker Change Linked to Breast Cancer
Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: Prostaglandin Inhibition to Prevent Breast Cancer

Resource links provided by NLM:


Further study details as provided by Hartford Hospital:

Primary Outcome Measures:
  • PG synthesis and metabolism, through the measurement of PGE2, COX-2 and 15-PGDH in the breast [ Time Frame: approximately 30 days ] [ Designated as safety issue: No ]

    This will be measured from both baseline and completion samples

    1. PG synthesis and metabolism, through the measurement of 15-PGDH, COX-2, and PGE2 in the breast

    Rationale: 1,25(OH)2D, the active form of vitamin D, has been shown in vitro to decrease PGE2 both by interfering with its production and by increasing its breakdown, leading to lower cell proliferation. Celecoxib potentiated the antiproliferative effect, allowing a much lower dose of each agent when used in combination than in isolation.



Secondary Outcome Measures:
  • 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. [ Time Frame: approximately 30 days ] [ Designated as safety issue: No ]

    This will be measured from both baseline and completion samples.

    2. Proliferative activity in the breast, as measured by MD cell morphology

    Rationale: Both MD and NAF contain ductal epithelial cells, but MD samples contain more cells for cytologic review than NAF. Findings on MD cytology correlate with likelihood of breast cancer, NAF cytology relates to breast cancer risk and improves risk stratification, and bioactive food components can alter NAF cytology



Estimated Enrollment: 31
Study Start Date: January 2009
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: placebo & cholecalciferol 400 IU
In this arm, the placebo is in place of celecoxib and the current RDA for cholecalciferol is used the control of the cholecalciferol higher dose.
Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU
Take 1 capsule from each bottle (1 bottle containing either placebo/celecoxib and 1 bottle containing either cholecaliferol 400 IU/cholecaliferol 2,000 IU) for 30 days
Other Names:
  • celecoxib (Celebrex)
  • cholecalciferol (vitamin D)
  • placebo (empty capule inside empty capsule
Active Comparator: placebo & cholecalciferol 2,000 IU
Placebo & cholecalciferol 2,000 IU
Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU
Take 1 capsule from each bottle (1 bottle containing either placebo/celecoxib and 1 bottle containing either cholecaliferol 400 IU/cholecaliferol 2,000 IU) for 30 days
Other Names:
  • celecoxib (Celebrex)
  • cholecalciferol (vitamin D)
  • placebo (empty capule inside empty capsule
Experimental: celecoxib 400mg & cholecalciferol 2,000 IU
celecoxib 400 mg & cholecalciferol2,000 IU
Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU
Take 1 capsule from each bottle (1 bottle containing either placebo/celecoxib and 1 bottle containing either cholecaliferol 400 IU/cholecaliferol 2,000 IU) for 30 days
Other Names:
  • celecoxib (Celebrex)
  • cholecalciferol (vitamin D)
  • placebo (empty capule inside empty capsule

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

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01769625

Locations
United States, North Dakota
University of North Dakota
Grand Forks, North Dakota, United States, 58202
Sponsors and Collaborators
Hartford Hospital
Susan G. Komen Breast Cancer Foundation
Investigators
Principal Investigator: Edward R. Sauter, MD, PhD, M.H.A University of North Dakota
  More Information

Responsible Party: Edward Sauter, MD, PhD, M.H.A, The University of Texas Health Science Center at Tyler
ClinicalTrials.gov Identifier: NCT01769625     History of Changes
Other Study ID Numbers: 200807-001 
Study First Received: January 14, 2013
Last Updated: May 11, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Hartford Hospital:
breast
high risk women
biomarkers
vitamin D

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vitamins
Vitamin D
Cholecalciferol
Celecoxib
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anti-Inflammatory Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 21, 2016