Finding the Best Tamoxifen Dose for Breast Cancer Risk Reduction in Premenopausal Women, RENAISSANCE Trial
Refining Tamoxifen Dose for Premenopausal Breast Cancer Risk Reduction (RENAISSANCE): A Phase II Single Arm Trial
9 other identifiers
interventional
200
1 country
11
Brief Summary
This phase II trial evaluates response-guided low-dose tamoxifen for reducing breast density in women who are at higher than average risk for breast cancer. Increasing breast density is a well established risk factor for breast cancer. Tamoxifen is a selective estrogen receptor modulator. It works by blocking the effects of the hormone estrogen in the breast. Tamoxifen has been shown to reduce breast density, even at reduced dosages, and is approved for the prevention of breast cancer.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Sep 2024
Typical duration for phase_2
11 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 27, 2023
CompletedFirst Posted
Study publicly available on registry
December 28, 2023
CompletedStudy Start
First participant enrolled
September 27, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 30, 2028
May 4, 2026
March 1, 2026
3.5 years
December 27, 2023
May 1, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Proportion of women who have a response at any time point
Tamoxifen response is defined as absolute dense area reduction (aDAR) of \>= 10% on mammogram compared to baseline mammogram. A one sample exact binomial test for one proportion will be used, and the exact two-sided p-value will be reported. Response rate for the entire study population, as well as for the group of women who were dose-escalated, will be estimated and reported with the corresponding 95% confidence interval. Absolute and relative changes in dense area will be estimated using descriptive statistics (e.g., mean and standard deviation, or median and interquartile range), and, as a sensitivity analysis, a paired t-test or the signed rank test will be used to determine whether there was a reduction in dense area. Similar descriptive statistics will be performed in each dose sequence group for both the response rate and dense area changes.
At 6, 12, and 18 months
Secondary Outcomes (5)
Plasma levels of major tamoxifen (TAM) metabolites
At 6, 12, and 18 months
Longitudinal change in serum biomarkers of tamoxifen response
From baseline up to 18 months
Baseline dense area
Up to 18 months
Patient-reported symptoms
At baseline, 6, 12, and 18 months
Adherence to final tamoxifen dose
Up to 18 months
Other Outcomes (3)
Breast tissue-based biomarkers
At 6 months
Single nucleotide polymorphisms (SNPs)
Up to 18 months
Change in breast cancer risk estimates
From baseline to 18 months
Study Arms (1)
Prevention (tamoxifen)
EXPERIMENTALParticipants receive tamoxifen 5mg PO QD for 6 months. Participants with aDAR \>= 10% on mammogram at 6 months continue receiving tamoxifen 5mg PO QD for 12 months. Participants with aDAR \< 10% at 6 months are escalated to receive tamoxifen 10mg PO QD for 6 months. Participants with aDAR \>= 10% after 6 months of tamoxifen 10mg continue receiving tamoxifen 10 mg PO QD for 6 months. Participants with aDAR \< 10% after 6 months of tamoxifen 10mg are given the option of continuing tamoxifen 10mg or escalating to receive tamoxifen 20mg PO QD for 6 months. Participants undergo mammography and collection of blood samples at screening and on study. Participants may optionally undergo biopsy at screening and on study.
Interventions
Undergo collection of blood samples
Eligibility Criteria
You may qualify if:
- Premenopausal women at the time of enrollment defined by any of the following:
- Age under 50 years and regular menstruation (most recent period within the past 3 months)
- Age under 50 years and continuous hormonal contraception use and at least one intact ovary
- Women who are not postmenopausal based on serum hormone levels. Women with estradiol =\< 30 pg/mL, follicle-stimulating hormone (FSH) \>= 30 IU/mL are eligible
- Women with any of the following:
- A history of unilateral estrogen receptor (ER) positive ductal carcinoma in situ (DCIS) with local therapy completed (as determined by treating physician recommendation and patient acceptance) at least 1 month prior to study entry. (The untreated breast will be the study breast, for both imaging and optional biopsy)
- Recent or prior lobular carcinoma in situ (LCIS), or any form of epithelial atypia, flat epithelial (FEA), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH)
- Are risk eligible for preventive medication based on a five-year risk of 1.7% or greater, estimated with a validated model: the National Cancer Institute (NCI) Breast Cancer Risk Assessment Tool, Tyrer-Cusick, Breast Cancer Surveillance Consortium. If the Tyrer-Cuzick model is used a ten-year risk of 3.4% or greater is acceptable
- Are tamoxifen-eligible by American Society of Clinical Oncology (ASCO) guidelines (\>= 2-fold increased risk compared to peer if age \>= 45 years, and \>= 4-fold increased risk if age \< 45 years)
- A history of mantle radiotherapy
- A moderate penetrance germline pathogenic variant
- Participants ≥ 18 and ≤ 55 years old will be enrolled. Our trial objectives are not relevant to females under 18 years of age since breast cancer is extraordinarily rare in this age group, and there are no guidelines regarding use of tamoxifen in children, even if know to be at very high risk for breast cancer when older. Because no dosing or adverse event (AE) data are currently available on the use of tamoxifen in participants \< 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status must be =\< 2 (Karnofsky \>= 60%)
- Human immunodeficiency virus (HIV)-infected patients are eligible to participate if they are on effective anti-retroviral therapy with undetectable viral load within the prior 6 months
- Women with evidence of chronic hepatitis B virus (HBV) infection, are also eligible if the HBV viral load is undetectable; they may be on suppressive therapy, if indicated
- +7 more criteria
You may not qualify if:
- BIRADS breast density category A on most recent mammogram
- History of selective estrogen receptor modulator (SERM) use within the past 5 years unless:
- Use was less than 6 months duration in the past 5 years and not used in the 1 year prior to enrollment OR
- Use was no greater than 2 months duration in the past 1 year and not used in the 6 months prior to enrollment
- History of invasive breast cancer
- Prior bilateral mastectomy or breast augmentation surgery including breast implants. Prior bilateral excisional surgical biopsy, mastopexy (breast lift) or mammoplasty (breast reduction) is allowed, as long as \> 1 year has passed since the procedure
- Women with "mosaic mammographic screening views", i.e., whose larger breast size precludes being imaged within a single mammographic screening view
- Current use of a strong CYP3A4 inducer or a strong CYP2D6 inhibitor unless willing and able to discontinue use and switch to an alternative medication for the duration of participation, under the advice of their physician. If the physician believes the current medication cannot be replaced, the participant will not be eligible
- Current use of Warfarin
- Planning to become pregnant within the next two years. Potential study participants will be questioned about this and excluded if they are planning pregnancy over the next 20 months
- History of thromboembolism, pulmonary embolism, thrombotic stroke, arterial thrombosis of the extremity or deep vein thrombosis. A history of superficial thrombophlebitis is allowed
- History of uterine cancer or atypical uterine hyperplasia with uterus intact
- Participants may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to tamoxifen
- Uncontrolled intercurrent illness or psychiatric illness/social situations that would limit compliance with study requirements
- +4 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (11)
University of Arizona Cancer Center - Prevention Research Clinic
Tucson, Arizona, 85719, United States
Northwestern University
Chicago, Illinois, 60611, United States
University of Illinois College of Medicine - Chicago
Chicago, Illinois, 60612, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Brigham and Women's Hospital
Boston, Massachusetts, 02115, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Medical University of South Carolina
Charleston, South Carolina, 29425, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Seema A Khan
Northwestern University
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 27, 2023
First Posted
December 28, 2023
Study Start
September 27, 2024
Primary Completion (Estimated)
March 31, 2028
Study Completion (Estimated)
September 30, 2028
Last Updated
May 4, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
"NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page."