Clinical trial NCT04067726: RANKL Inhibition and Mammographic Breast Density
Official title: Randomized Clinical Trial of RANKL Inhibition With Denosumab on Mammographic Density in Premenopausal Women With Dense Breasts (TRIDENT)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Dense Breasts
Keywords: Mammographic density
Breast cancer
RANKL
Denosumab
Prevention
Premenopausal
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
First posted: 2019-08-26
Enrollment: 210
Sex: FEMALE
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Stratified permuted block randomized design will be used to generate the randomization table where permuted block randomization will be used for each stratum by age, with a varying block size of 4 and 6.
Primary purpose: PREVENTION

Brief summary: Data supporting a role for RANKL signaling in mammographic density and breast cancer development has begun to emerge, but clinical trial data providing definitive evidence that would allow the adoption of RANKL inhibition in primary breast cancer prevention are not yet available. The hypothesis is that RANKL inhibition with denosumab will decrease mammographic density in high-risk premenopausal women with dense breasts. To address this, the investigators have developed this clinical trial to quantify the impact of RANKL inhibition on mammographic density in high-risk premenopausal women with dense breasts and to determine the effect of RANKL inhibition on markers of proliferation and biomarkers of breast cancer risk. Successful demonstration that RANKL inhibition reduces mammographic density could open up additional approaches to primary breast cancer prevention in high-risk premenopausal women, who do not have dominant genetic predisposition.


Eligibility criteria: Inclusion Criteria:

* Female.
* Premenopausal (when menopausal status is uncertain, the investigators will measure follicle-stimulating hormone and estradiol to ascertain that a partcipant is premenopausal)
* At least 40 years of age.
* Dense breasts on routine mammogram (BI-RADS Category C and D)
* Able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

* History of breast or any other invasive cancer except for DCIS (ductal carcinoma in situ) who received only lumpectomy, LCIS (lobular carcinoma in situ), atypical hyperplasia, non-melanoma skin cancer, carcinoma in situ of the cervix.
* Current use of tamoxifen, aromatase inhibitors, or bisphosphonates, or RANKL inhibitors
* Concurrent participation in another cancer chemoprevention trial (unless no longer receiving the intervention).
* Pregnant, lactating, or planning to get pregnant while the trial is ongoing.
* Recent history of invasive dental procedure (e.g. tooth extraction, dental implant, oral surgery).
* Unhealed and/or planned dental/oral surgery.
* History of osteonecrosis/osteomyelitis of the jaw.
* History of osteoporosis or severe osteopenia.

Primary outcomes:
measure: Change in mammographic breast density between the two arms as measured by volumetric percent density
timeFrame: From baseline to 12 months
Secondary outcomes:
measure: Change in mammographic breast density between the two arms as measured by volumetric percent density
timeFrame: From baseline to 24 months
measure: Change in mammographic breast density between the two arms as measured by volumetric percent density
timeFrame: From 12 months to 24 months
measure: Change in expression gene related to RANK in breast tissue compared between the two arms
timeFrame: Baseline and 12 months
measure: Change in expression gene related to progesterone in breast tissue compared between the two arms
timeFrame: Baseline and 12 months
measure: Change in expression gene related to metabolics in breast tissue compared between the two arms
timeFrame: Baseline and 12 months
measure: Change in expression gene related to immune in breast tissue compared between the two arms
timeFrame: Baseline and 12 months
measure: Change in expression gene related to inflammatory in breast tissue compared between the two arms
timeFrame: Baseline and 12 months
measure: Change in expression of markers of breast epithelial and stromal proliferation compared between the two arms
timeFrame: Baseline and 12 months
measure: Change in breast metabolome compared between the two arms
timeFrame: Baseline and 12 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Adetunji T Toriola, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: