Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer

NCT05941520 | Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: NCI-2023-05217UMCC 2022.055UMI22-09-01P30CA046592UG1CA242632
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 4

Brief Summary

This phase IIA trial compares the effect of acolbifene versus low dose tamoxifen in preventing breast cancer in premenopausal women at high risk for developing breast cancer. The usual approach for patients at increased risk for breast cancer is to undergo yearly breast magnetic resonance imaging or ultrasound in addition to yearly mammogram. Premenopausal women at very high lifetime risk for breast cancer (greater than 50%) can consider preventive removal (mastectomy) of both breasts. Premenopausal women age 35 or older with a prior diagnosis of atypical hyperplasia, lobular carcinoma in situ, or an estimated 10-year risk of greater than or equal to 3% or estimated 10-year risk of greater than or equal to 2-5 times that of the average woman (depending on age) may be advised to consider five years of standard dose tamoxifen. Standard dose tamoxifen is four times the dose used in this study. Estrogen can cause the development and growth of breast cancer cells. Acolbifene and tamoxifen blocks the use of estrogen by breast cells. This study may help researchers measure the effects of acolbifene and low dose tamoxifen on markers of breast cancer risk in mammogram imaging, breast tissue, and in blood samples.

Conditions

Breast Lobular Carcinoma In Situ; Breast Ductal Carcinoma In Situ; Breast Carcinoma; Breast Atypical Hyperplasia

Outcome Measures

Primary Outcomes (1)

• Change in the relative abundance of the specific sequence of messenger ribonucleic acid that codes for AGR2

  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.

  Baseline up to 6 months

Secondary Outcomes (5)

• Change in Estrogen Response Gene Index (ERGI)

  Baseline up to 6 months

• Relative change in mammographic absolute fibroglandular volume

  Baseline up to 6 months

• Relative change in mammographic percentage (%) dense volume

  Baseline up to 6 months

• Change in Menopause-Specific Quality of Life (MENQOL)

  Baseline up to 6 months

• Change in Hot Flash Score

  Baseline up to 6 months

Study Arms (2)

Group 1 (acolbifene)

EXPERIMENTAL

Patients receive acolbifene PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo 3D mammography and collection of blood samples during screening and at the end of acolbifene treatment. In addition, patients undergo RPFNA during screening and during day 1-10 of their menstrual cycle, or if not menstruating, at the convenience of the patient and study staff.

Drug: Acolbifene Hydrochloride; Procedure: Biospecimen Collection; Other: Questionnaire Administration; Procedure: Random Periareolar Fine-Needle Aspiration

Group 2 (tamoxifen)

ACTIVE COMPARATOR

Patients receive tamoxifen PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo 3D mammography and collection of blood samples during screening and at the end of tamoxifen treatment. In addition, patients undergo RPFNA during screening and day 1-10 of their menstrual cycle, or if not menstruating, at the convenience of the patient and study staff.

Procedure: Biospecimen Collection; Procedure: Mammography; Other: Questionnaire Administration; Procedure: Random Periareolar Fine-Needle Aspiration; Drug: Tamoxifen

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Group 1 (acolbifene); Group 2 (tamoxifen)

Mammography PROCEDURE

Undergo 3D mammography

Also known as: MG

Group 2 (tamoxifen)

Questionnaire Administration OTHER

Ancillary studies

Group 1 (acolbifene); Group 2 (tamoxifen)

Random Periareolar Fine-Needle Aspiration PROCEDURE

Undergo RPFNA

Also known as: Random Periareolar Fine Needle Aspiration, RPFNA

Group 1 (acolbifene); Group 2 (tamoxifen)

Tamoxifen DRUG

Given PO

Also known as: TMX

Group 2 (tamoxifen)

Acolbifene Hydrochloride DRUG

Given PO

Group 1 (acolbifene)

Eligibility Criteria

• Age: 35 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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) is being used which suppresses menstrual periods, or premenopausal women who have undergone a hysterectomy, but ovaries are intact
• Not considering pregnancy for at least 12 months
• Women of child-bearing potential capacity 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 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 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)

You may not qualify if:

• 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 BRCA1/2 or PALB2 (These latter individuals are likely to undergo yearly ovarian screening and enlarging cysts could raise concern about ovarian cancer and lead to unnecessary diagnostic procedures)
• 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 would not be able to or do not wish 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. Women who would be able to stop daily use of aspirin and aspirin containing products at least 3 weeks prior to each RPFNA are eligible
• NOTE: Women may resume daily use of aspirin and aspirin containing products 3 days after each RPFNA procedure
• Starting or stopping oral contraceptives (OCs) or hormonal progestin IUDs within 8 weeks of baseline RPFNA

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (4)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Breast Carcinoma In Situ

Interventions

Specimen Handling; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Carol J Fabian

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 11, 2023
• First Posted: July 12, 2023
• Study Start: August 23, 2024
• Primary Completion (Estimated): August 23, 2027
• Study Completion (Estimated): September 1, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (4)