Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer
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ClinicalTrials.gov Identifier: NCT05941520 |
Recruitment Status :
Not yet recruiting
First Posted : July 12, 2023
Last Update Posted : April 15, 2024
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Tracking Information | |||||||
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First Submitted Date ICMJE | July 11, 2023 | ||||||
First Posted Date ICMJE | July 12, 2023 | ||||||
Last Update Posted Date | April 15, 2024 | ||||||
Estimated Study Start Date ICMJE | October 8, 2024 | ||||||
Estimated Primary Completion Date | September 1, 2026 (Final data collection date for primary outcome measure) | ||||||
Current Primary Outcome Measures ICMJE |
Change in the relative abundance of the specific sequence of messenger ribonucleic acid (mRNA) that codes for AGR2 [ Time Frame: Baseline up to 6 months ] Will be assessed in benign breast tissue acquired by random periareolar fine-needle aspiration (RPFNA). 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 (FC) 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.
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Original Primary Outcome Measures ICMJE | Same as current | ||||||
Change History | |||||||
Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE | Same as current | ||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||
Descriptive Information | |||||||
Brief Title ICMJE | Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer | ||||||
Official Title ICMJE | Phase IIA Trial of Acolbifene (20 mg) vs Low Dose Tamoxifen (5 mg) in Pre-Menopausal Women at High Risk for Development of Breast Cancer | ||||||
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 (MRI) 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. | ||||||
Detailed Description | PRIMARY OBJECTIVE: I. To determine if there is a difference in change in expression of the endocrine resistance gene anterior gradient 2 (AGR2) in benign breast tissue of premenopausal women at increased risk for breast cancer randomized to acolbifene 20 mg vs tamoxifen 5 mg orally daily for 6 months. SECONDARY OBJECTIVES: I. To determine if there is significant within-arm effect of 6 months of acolbifene 20 mg or tamoxifen 5 mg as assessed on the Estrogen Response Gene Index (ERGI) in benign breast tissue. II. To determine if there is significant within-arm effect of 6 months of acolbifene 20 mg or tamoxifen 5 mg on mammographic density as measured by relative change in % dense area (LIBRA [Trademark]). III. Assess the feasibility of assessment of change in absolute fibroglandular volume (FGV) and % dense volume (Volpara [Trademark]) in a multisite trial. IV. To determine if there is a significant within-arm effect of 6 months of acolbifene 20 mg or tamoxifen 5 mg on Menopause-Specific Quality of Life Questionnaire (MENQOL) or Hot Flash Score. EXPLORATORY OBJECTIVES: I. Assess within arm change in breast epithelial cell protein expression of Ki-67 in specimens with >= 2% baseline Ki-67. II. Assess within arm change in bioavailable serum estradiol, testosterone, progesterone. III. Association of baseline AMH (>= 1 ng/ml associated with normal ovarian reserve) with 6-month serum estradiol and change in tissue estrogen responsive gene expression (ERGI and AGR2). IV. Association of tamoxifen and acolbifene parent drug and active metabolite levels with change in tissue estrogen response genes and mammographic density. V. Assess within arm change of AGR2, FOXA1, estrogen receptor (ER), progesterone receptor (PR) by immunohistochemistry (IHC) on residual fixed random periareolar fine needle aspiration (RPFNA) specimens processed to blocks. VI. Assess within arm change in metabolic measures including triglycerides, measures of insulin sensitivity and thyroid binding globulin (University of Kansas Medical Center [KUMC] participants only). OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive acolbifene orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity. Patients also undergo three-dimensional (3D) mammography and collection of blood samples during screening and at the end of acolbifene treatment. In addition, patients undergo RPFNA during screening and on day 1-10 of their menstrual cycle, or if not menstruating, at the convenience of the patient and study staff. GROUP II: 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. After completion of study treatment, patients are followed up between 21-35 days. |
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Study Type ICMJE | Interventional | ||||||
Study Phase ICMJE | Phase 2 | ||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Prevention |
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Condition ICMJE |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Not Provided | ||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||||||
Recruitment Status ICMJE | Not yet recruiting | ||||||
Estimated Enrollment ICMJE |
80 | ||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||
Estimated Study Completion Date ICMJE | September 1, 2028 | ||||||
Estimated Primary Completion Date | September 1, 2026 (Final data collection date for primary outcome measure) | ||||||
Eligibility Criteria ICMJE | Inclusion Criteria:
Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 35 Years and older (Adult, Older Adult) | ||||||
Accepts Healthy Volunteers ICMJE | No | ||||||
Contacts ICMJE | |||||||
Listed Location Countries ICMJE | United States | ||||||
Removed Location Countries | |||||||
Administrative Information | |||||||
NCT Number ICMJE | NCT05941520 | ||||||
Other Study ID Numbers ICMJE | NCI-2023-05217 NCI-2023-05217 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) UMCC 2022.055 ( Other Identifier: University of Michigan Comprehensive Cancer Center ) UMI22-09-01 ( Other Identifier: DCP ) P30CA046592 ( U.S. NIH Grant/Contract ) UG1CA242632 ( U.S. NIH Grant/Contract ) |
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Has Data Monitoring Committee | Yes | ||||||
U.S. FDA-regulated Product |
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IPD Sharing Statement ICMJE |
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Current Responsible Party | National Cancer Institute (NCI) | ||||||
Original Responsible Party | Same as current | ||||||
Current Study Sponsor ICMJE | National Cancer Institute (NCI) | ||||||
Original Study Sponsor ICMJE | Same as current | ||||||
Collaborators ICMJE | Not Provided | ||||||
Investigators ICMJE |
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PRS Account | National Cancer Institute (NCI) | ||||||
Verification Date | April 2024 | ||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |