Ignite Creation Date:
2025-12-25 @ 4:22 AM
Ignite Modification Date:
2025-12-26 @ 3:25 AM
Study NCT ID:
NCT05941520
Status:
RECRUITING
Last Update Posted:
2025-10-07
First Post:
2023-07-11
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Acolbifene Versus Low Dose Tamoxifen for the Prevention of Breast Cancer in Premenopausal Women at High Risk for Development of Breast Cancer
Sponsor:
National Cancer Institute (NCI)
Organization:
Study Overview
Official Title:
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
Status:
RECRUITING
Status Verified Date:
2025-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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 versus (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 change in fibroglandular volume (FGV) and mammographic percent dense volume.
III. 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 anti-Mullerian hormone (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, Forkhead box protein A1 (FOXA1), estrogen receptor (ER), progesterone receptor (PR) proteins on residual fixed specimens acquired by random periareolar fine needle aspiration (RPFNA) and processed to blocks.
VI. Assess within arm change in metabolic measures including triglycerides, measures of insulin sensitivity and thyroid binding globulin (Kansas University 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.
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 versus (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 change in fibroglandular volume (FGV) and mammographic percent dense volume.
III. 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 anti-Mullerian hormone (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, Forkhead box protein A1 (FOXA1), estrogen receptor (ER), progesterone receptor (PR) proteins on residual fixed specimens acquired by random periareolar fine needle aspiration (RPFNA) and processed to blocks.
VI. Assess within arm change in metabolic measures including triglycerides, measures of insulin sensitivity and thyroid binding globulin (Kansas University 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.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2023-05217 | REGISTRY | CTRP (Clinical Trial Reporting Program) | View | |
| UMCC 2022.055 | OTHER | University of Michigan Comprehensive Cancer Center | View | |
| UMI22-09-01 | OTHER | DCP | View | |
| P30CA046592 | NIH | None | https://reporter.nih.gov/quic… | View |
| UG1CA242632 | NIH | None | https://reporter.nih.gov/quic… | View |