Changes in Biomarkers Using Prostaglandin Inhibitors

Hartford Hospital

Status and phase: Completed; Phase 2; Phase 1

Conditions: Biomarker Change Linked to Breast Cancer

Treatments: Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU

Study type: Interventional

Funder types: Other

Identifiers

NCT01769625

200807-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 31 patients

Sex: Female

Ages: 18+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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31 participants in 3 patient groups, including a placebo group

placebo & cholecalciferol 400 IU

Placebo Comparator group

Description:

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.

Treatment:

Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU

placebo & cholecalciferol 2,000 IU

Active Comparator group

Description:

Placebo \& cholecalciferol 2,000 IU

Treatment:

Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU

celecoxib 400mg & cholecalciferol 2,000 IU

Experimental group

Description:

celecoxib 400 mg \& cholecalciferol2,000 IU

Treatment:

Drug: placebo/celecoxib 400 mg and cholecalciferol 400 IU/cholecalciferol 2,000 IU