Changes in Breast Cancer Biomarkers Using Synergistic Prostaglandin Inhibitors

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2013 by The University of Texas Health Science Center at Tyler
Sponsor:
Collaborators:
University of North Dakota
Information provided by (Responsible Party):
Edward Sauter, The University of Texas Health Science Center at Tyler
ClinicalTrials.gov Identifier:
NCT01425476
First received: April 26, 2011
Last updated: January 14, 2013
Last verified: January 2013
  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), 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
Breast Cancer
Drug: Celecoxib
Drug: Placebo
Drug: Cholecalciferol
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: Breast Cancer Prevention Using Synergistic Prostaglandin Inhibitors (The Vitamin D/Celecoxib Study)

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at Tyler:

Primary Outcome Measures:
  • PG synthesis and metabolism [ 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, as measured by MD cell morphology [ 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.


  • Circulating levels of 25(OH)D, 1,25(OH)2D, and celecoxib [ Time Frame: approximately 30 days ] [ Designated as safety issue: No ]

    This will be measured from both baseline and completion samples.

    3. Circulating levels of 25(OH)D, 1,25(OH)2D, and celecoxib, and determine if the levels of these compounds correlate with response to markers of PG synthesis and metabolism or cell proliferation.



Estimated Enrollment: 45
Study Start Date: July 2008
Estimated Primary Completion Date: August 2014 (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
Take one tablet from each bottle (one bottle containing either placebo/celecoxib and one bottle containing either cholecalciferol 400 IU or 2,000 IU) daily for 30 days.
Other Name: placebo (empty capsule inside an empty capsule)
Drug: Cholecalciferol
Take one tablet from each bottle (one bottle containing either placebo/celecoxib and one bottle containing either cholecalciferol 400 IU or 2,000 IU) daily for 30 days.
Other Name: cholecalciferol (Vitamin D)
Active Comparator: Placebo & cholecalciferol 2,000 IU Drug: Placebo
Take one tablet from each bottle (one bottle containing either placebo/celecoxib and one bottle containing either cholecalciferol 400 IU or 2,000 IU) daily for 30 days.
Other Name: placebo (empty capsule inside an empty capsule)
Drug: Cholecalciferol
Take one tablet from each bottle (one bottle containing either placebo/celecoxib and one bottle containing either cholecalciferol 400 IU or 2,000 IU) daily for 30 days.
Other Name: cholecalciferol (Vitamin D)
Experimental: celecoxib 400 mg & cholecalciferol 2,000 IU Drug: Celecoxib
Take one tablet from each bottle (one bottle containing either placebo/celecoxib and one bottle containing either cholecalciferol 400 IU or 2,000 IU) daily for 30 days.
Other Name: celecoxib (Celebrex)
Drug: Cholecalciferol
Take one tablet from each bottle (one bottle containing either placebo/celecoxib and one bottle containing either cholecalciferol 400 IU or 2,000 IU) daily for 30 days.
Other Name: cholecalciferol (Vitamin D)

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 high risk for breast cancer (gail risk >/= 1.66% for 5 year risk, or personal or family history)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:

In women at increased breast cancer risk, determine the effect of vitamin D, with or without celecoxib, on

  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.

  2. Proliferative activity in the breast, as measured by Mammary Ductoscopy (MD) cell morphology

    Rationale: Both MD and Nipple Aspirate Fluid (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 (2), NAF cytology relates to breast cancer risk and improves risk stratification (3), and bioactive food components can alter NAF cytology (4).

  3. Circulating levels of 25(OH)D, 1,25(OH)2D, and celecoxib, and determine if the levels of these compounds correlate with response to markers of PG synthesis and metabolism or cell proliferation.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Women 18 years of age or older
  • Increased risk for breast cancer (demonstrated by strong family history [one 1st degree or two 2nd degree relatives], history of DCIS, IBC, or precancerous changes in breasts). OR Gail Model risk of developing IBC in a 5-year period of >1.66%
  • Women with a history of breast cancer, must be free of disease and finished with treatment
  • 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 candidate
  • 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: NCT01425476

Contacts
Contact: Edward Sauter, MD, PhD 701-777-2284 edward.sauter@med.und.edu

Locations
United States, North Dakota
University of North Dakota Recruiting
Grand Forks, North Dakota, United States, 58203
Contact: Edward Sauter, MD, PhD    701-777-2284    edward.sauter@med.und.edu   
Principal Investigator: Edward Sauter, MD, PhD         
Sub-Investigator: Robert Sticca, MD         
Sponsors and Collaborators
The University of Texas Health Science Center at Tyler
University of North Dakota
Investigators
Principal Investigator: Edward Sauter, MD, PhD University of North Dakota
  More Information

No publications provided

Responsible Party: Edward Sauter, MD, PhD, M.H.A, The University of Texas Health Science Center at Tyler
ClinicalTrials.gov Identifier: NCT01425476     History of Changes
Other Study ID Numbers: 200806
Study First Received: April 26, 2011
Last Updated: January 14, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by The University of Texas Health Science Center at Tyler:
breast
high risk women
biomarkers
vitamin D

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Prostaglandin Antagonists
Celecoxib
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
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
Therapeutic Uses
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 26, 2014