Acolbifene vs. Tamoxifen for Breast Cancer Prevention
This study is comparing two medicines, acolbifene and low-dose tamoxifen, to see which is better at preventing breast cancer in premenopausal women who are at high risk. You might be eligible if you are a woman aged 35 or older, are premenopausal, and have certain breast conditions like atypical hyperplasia or lobular carcinoma in situ, or a high estimated risk of breast cancer. The main goal is to see how these medicines change a specific gene (AGR2) in your breast tissue over 6 months. This helps researchers understand how these drugs might work to prevent cancer.
- Study design
- This is a Phase IIA interventional study comparing acolbifene to low-dose tamoxifen, with a planned enrollment of 80 participants.
- What's involved
- You would take either acolbifene or tamoxifen daily for 6 months. You would also have blood collected, 3D mammograms, complete questionnaires, and undergo a random periareolar fine-needle aspiration (RPFNA).
- Compensation
- Not stated in the trial record.
- Follow-up
- The primary endpoint measures changes up to 6 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05941520
Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer
Recruiting
PHASE2Ages 35+InterventionalPreventionNational Cancer Institute (NCI)Government-funded
~80 participants
Updated 2026-07-07 on ClinicalTrials.gov
What's tested:Acolbifene HydrochlorideBiospecimen CollectionMammographyQuestionnaire AdministrationRandom Periareolar Fine-Needle AspirationTamoxifen
At a glance
Recruiting sites
4 of 4 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Change in the relative abundance of the specific sequence of messenger ribonucleic acid that codes for AGR2
Measured over Baseline up to 6 months
Conditions
Where it's being run
4 sites across 4 statesCalifornia1
Illinois1
Kansas1
Ohio1
Study leadership
- Carol J Fabian · PRINCIPAL_INVESTIGATOR · University of Kansas Medical Center
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Age \>= 35 years
Considered clinically premenopausal
Having regular menstrual cycles (between 21 and 35 days) unless a contraceptive device such as progestin containing intrauterine device (IUD) (e.g., Mirena IUD) or oral contraceptives is being used which suppresses menstrual periods, or premenopausal women who have undergone a hysterectomy, but have at least one intact ovary
Not considering pregnancy for at least 12 months
Women of child-bearing potential capacity who are heterosexually active must be willing to have used effective birth control precautions for 8 weeks prior to fine needle aspiration and be willing to continue for 8 weeks after study completion as tamoxifen may have teratogenic effects on the developing fetus. Reproductive and developmental toxicity studies have not been conducted with acolbifene. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must stop study drug and inform her study physician immediately.
For women who are heterosexually active not using oral contraceptive (progestin alone or estrogen plus a progestin), two of the following are recommended but woman must agree to at least one of the following methods:
IUD non-hormonal or hormone containing (usually a progestin) intrauterine device (IUD) or rings. Any of these should have been inserted at least 8 weeks prior to RPFNA.
Barrier method (such as condoms and diaphragms or cervical caps with or without a spermicide)
Partner has had a vasectomy.
For women who are heterosexually active using oral contraceptive (progestin alone or estrogen plus a progestin), woman must agree to at least a non- hormonal IUD or a barrier method (below) or her partner must have had a vasectomy:
Non-hormonal IUD
Barrier method (such as condoms and diaphragms or cervical caps with or without a spermicide)
Partner has had a vasectomy
Must have increased breast cancer risk as predicted by any one or more of the conditions listed below or increased model calculated risk as below:
Any one or more of the following conditions associated with increased risk (condition must be documented in electronic medical record or copy of relevant pathology or genetic testing reports submitted with the eligibility checklist)
A prior biopsy at any time in the past showing ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), atypical hyperplasia. (If DCIS must have been treated by mastectomy or local excision +/- radiation with this treatment completed at least 3 months prior to screening with RPFNA)
High or moderate penetrance risk pathogenic or likely pathogenic germline gene mutation in ATM, BARD1, BRIP1, CDH1, CHEK2, MSH6, NBN, NF1, PTEN, PMS2, RAD51C, RAD51D, TP53, BRCA2, or PALB2
High polygenic risk score (Life-time risk of \>= 2x average or 25%)
Breast cancer in a first or second degree relative (female or male) with onset under age 50. First degree relative is defined as parent, sibling, or child. Second degree relative is defined as grandparent, uncle, aunt, nephew, niece, half-sibling, grandchild or first cousin
Two or more affected first or second-degree relatives from either the maternal or paternal lineage without regard to age
Bilateral breast cancer or breast and ovarian cancer in the same first or second degree relative without regard to age.
High mammographic density defined as either visual estimate of area of density (VAS) \> 50%, or Volpara (Trademark) \>= 15% dense volume (Volpara d) or Breast Imaging Reporting and Data System (BIRADS) assessment of extremely dense (BIRADs D)
Chest irradiation prior to age 30
Alternatively, instead of conditions listed above, an increased risk of breast cancer as calculated by International Breast Cancer Intervention Study Version 8 (IBIS 8), or Breast Cancer Surveillance Consortium (BCSC) 3 by one or more of the following criteria:
10-year risk of breast cancer of \>= 3%
Increase in age specific 10-year relative risk by age group
Age 35-39 10-year relative risk of \>= 5X that for age group
Age 40-44 10-year risk of \>= 4X that for age group
Age 45 and up 10-year risk of \>= 2X
IBIS Version 8 Remaining lifetime risk of \>= 25% or \>= 2X that of population
A copy of the output of model calculations from IBIS 8 (https://ems-trials.org/riskevaluator/), or BCSC version 3.0 (https://tools.bcsc-scc.org/BC5yearRisk/calculator.htm) online tools, if used for qualifying risk assessment, or polygenetic risk score should be submitted with the eligibility checklist. Otherwise, these risk qualifying factors need to be documented in the medical record if that is considered the source document
Women must have at least 1 unaffected untreated breast for fine needle aspiration. Women may have had prior unilateral breast radiation or mastectomy for DCIS
Eastern Cooperative Oncology Group (ECOG) current performance status (PS) ≤ 2 as documented within 3 months prior to randomization or Karnofsky score \>= 60%
Total bilirubin =\< 1.5 x institutional upper limit of normal (measured within 180 days prior to randomization)
Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) =\< 1.5 x institutional upper limit of normal (measured within 180 days prior to randomization)
Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 1.5 x institutional upper limit of normal (measured within 180 days prior to randomization)
Creatinine =\< 2.0 mg/dL (measured within 180 days prior to randomization)
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures
Ability to understand and the willingness to sign a written informed consent document
Confirmation that fixed (Cytolyt™) and frozen tissue specimens have been received in good condition at KUMC and are likely adequate for assessment of the primary endpoint. Confirmation will be provided by Protocol PI(s) and/or KUMC Laboratory personnel
Confirmation that a Volpara™ Score Card or a Volpara Data Manager (VDM)-generated Excel file has been received at KUMC and archived for assessment of the secondary endpoint. Confirmation will be provided by Protocol PI(s) and/or KUMC study coordinator. Alternatively, confirmation may be provided by site personnel that a raw image file in Digital Imaging and Communications in Medicine (DICOM) format has been archived at the site such that it can be later used for generation of a Volpara™ Score Card or Excel file
Exclusion
Bilateral breast implants (danger of implant puncture with RPFNA)
Women who are pregnant
Currently breastfeeding (concern that tamoxifen or acolbifene may be in breast milk) or nursing within the past 12 months (concern about milk fistula with RPFNA)
Prior invasive breast cancer within the past 5 years
Other prior invasive cancer \> T1 stage (other than non-melanoma skin) within the past 5 years
Pathogenic or likely pathogenic germline mutation in BRCA1
Type I or Type II diabetes mellitus requiring treatment with prescription medication
Prior deep vein thrombosis, pulmonary embolus, or stroke
History of chronic liver disease including NASH (nonalcoholic steatohepatitis) and chronic hepatitis C
History of chronic hepatitis B or hepatitis C (danger of exacerbation of liver damage from hepatitis or tamoxifen-induced non-alcoholic fatty liver disease or non-alcoholic steatohepatitis)
History of human immunodeficiency virus (HIV)-infection (danger of exacerbation of underlying clinically inapparent liver damage caused by HIV and/or hepatotoxicity can be induced by interaction of tamoxifen-induced CYP3A4 with direct anti-hepatitis C virus \[HCV\] agents)
Current use of prescription anticoagulants such as Coumadin (warfarin), direct-acting oral anticoagulants such as Xarelto (rivaroxaban) or Eliquis (apixaban), or heparin
Women who, due to a medical condition, would not be able to discontinue daily use of aspirin (81 mg or higher) and aspirin containing products (81 mg or higher) at least 3 weeks prior to each RPFNA are not eligible
Starting or stopping oral contraceptives (OCs) or hormonal progestin IUDs within 8 weeks of baseline RPFNA
Current use or use within the prior 8 weeks of progesterone/progestin injections or progestin implants (due to concerns about high levels of progestin and lack of safety and efficacy data with low dose tamoxifen)
Current use of other investigational agents
Prior treatment with acolbifene for more than 2 months
Prior treatment with tamoxifen for more than 2 months
Current use of prescription immunosuppressive drugs
History of allergic reactions attributed to tamoxifen or acolbifene or compounds of similar chemical composition
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study
Use of GLP-1 or GIP receptor agonist within 8 weeks of enrollment or plan to use a GLP-1 or GIP receptor agonist during study participation
What this trial measures
- Change in the relative abundance of the specific sequence of messenger ribonucleic acid that codes for AGR2Baseline up to 6 months
Will be assessed in benign breast tissue acquired by random periareolar fine-needle aspiration. Change over the intervention period is expressed as the ratio of the relative abundance values (6-month value: baseline value) and then this fold change value is log transformed (base 2) for analysis. For this variable, values of zero indicate no change in the relative abundance of AGR2; positive values indicate an increase in the relative abundance; and negative values a decrease in the relative abundance.