Breast Atypical Ductal HyperplasiaPhase 2NCT06184750
Finding the Best Tamoxifen Dose for Breast Cancer Risk Reduction in Premenopausal Women, RENAISSANCE Trial
A Phase 2 study testing Biopsy Procedure, Biospecimen Collection and Mammography in people with Breast Atypical Ductal Hyperplasia and Breast Atypical Lobular Hyperplasia, run by National Cancer Institute (NCI) at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women only
- Conditions the study is for
- Breast Atypical Ductal Hyperplasia, Breast Atypical Lobular Hyperplasia, Breast Carcinoma
- What is being tested?
- Biopsy Procedure, Biospecimen Collection and Mammography
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 11 sitesUnited States
- Study dates
- 27 Sep 2024to 30 Sep 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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 and 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)
Show all 21Show fewer
- 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
- 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
- Women with a history of hepatitis C virus (HCV) infection are eligible if treated and cured. For those who are currently on treatment, they are eligible if they have an undetectable HCV viral load
- Women with herpes simplex virus (HSV) infection are eligible if on chronic or as needed (due to a flare) suppressive antiviral therapy
- Hormonal contraceptive users are eligible and should maintain the same hormonal contraceptive preparation throughout the duration of the trial. Changing hormonal contraception after enrollment for medical reasons is allowed
- The effects of tamoxifen on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because tamoxifen is known to be teratogenic, women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence; partner vasectomy) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Breast Imaging Reporting and Data System (BIRADS) 1 or 2. Women with BIRADS 3 findings that have been biopsied and shown to be benign or are stable at 6-months follow-up are allowed
- Women who are factor V leiden carriers and have not had a blood clot are eligible, if approved by their treating physician
Who cannot join
- BIRADS breast density category A
- 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
Show all 19Show fewer
- 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 at least 30 days prior to screening 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
- Pregnant women are excluded from this study because tamoxifen a category D agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with tamoxifen. Breastfeeding should be discontinued if the mother is treated with tamoxifen
- Women with known gene mutations associated with an increased risk for breast cancer such as BRCA1/2, CDH1, PALB2, PTEN, STK11, or P53
- Current use of sex hormones (estrogen, progesterone, or androgens), unless part of hormonal contraception pills
- Prior invasive cancer ≥ T1 (other than non-melanoma skin cancer), unless curatively treated, and all treatment was completed > 5 years prior to enrollment
Trial locations and contacts
11 sites in 1 country. Contact the study team or a site near you to ask about taking part.
11 sites in 1 country
United States11 sites, 10 recruiting
- Recruiting
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109
Melissa L. Pilewskie, 734-647-8902, mpilewsk@med.umich.edu
Melissa L. Pilewskie
- Withdrawn
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Judy E. Garber, 617-632-3891, judy_garber@dfci.harvard.edu
Judy E. Garber
- Recruiting
Medical University of South Carolina
Charleston, South Carolina, 29425
Kevin S. Hughes, 843-876-4420, hughkevi@musc.edu
Kevin S. Hughes
- Recruiting
Northwestern University
Chicago, Illinois, 60611
Seema A. Khan, 312-503-4236, s-khan2@northwestern.edu
Seema A. Khan
- Recruiting
University of Illinois College of Medicine - Chicago
Chicago, Illinois, 60612
Kent F. Hoskins, 312-996-1581, khoski@uic.edu
Kent F. Hoskins
- Recruiting
Case Western Reserve University
Cleveland, Ohio, 44106
Amanda L. Amin, 216-896-1787, amanda.amin@uhhospitals.org
Amanda L. Amin
- Recruiting
UT MD Anderson Cancer Center
Houston, Texas, 77030
Parijatham (Priya) S. Thomas, 713-792-6161, psthomas@mdanderson.org
Parijatham (Priya) S. Thomas
- Recruiting
University of Kansas Cancer Center
Kansas City, Kansas, 66160
Carol J. Fabian, 913-588-7791, cfabian@kumc.edu
Carol J. Fabian
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Adetunji T. Toriola, 314-286-2668, a.toriola@wustl.edu
Adetunji T. Toriola
- Recruiting
University of Arizona Cancer Center - Prevention Research Clinic
Tucson, Arizona, 85719
Sima Ehsani Chimeh, 520-626-2873, simaehsani@arizona.edu
Sima Ehsani Chimeh
About this study
Official title: Refining Tamoxifen Dose for Premenopausal Breast Cancer Risk Reduction (RENAISSANCE): A Phase II Single Arm Trial
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.
Read the detailed description
PRIMARY OBJECTIVE:
- To evaluate whether the overall proportion of premenopausal tamoxifen responders (defined by absolute dense area reduction on mammogram of > 10%) can be increased through a strategy of within-individual dose escalation among non-responders from 5 mg per day to 10 mg per day.
SECONDARY OBJECTIVES:
- To assess the association of plasma levels of major tamoxifen metabolites with tamoxifen dose and breast density changes from baseline.
II. To evaluate longitudinal change from baseline in serum biomarkers of tamoxifen response at each dose level: sex hormone binding globulin (SHBG), insulin like growth factor 1 (IGF-1) and C-reactive protein (CRP).
III. To assess the association of baseline dense area (continuous variable) with tamoxifen response.
IV. To evaluate the impact of tamoxifen dose on participant-reported symptoms (Breast Eight Symptom Scale, BESS).
- To evaluate the impact of tamoxifen dose on adherence to final tamoxifen dose.
EXPLORATORY OBJECTIVES:
- To evaluate breast tissue-based biomarkers (in research biopsy samples) that associate with tamoxifen response at six months, comparing within-person change in responders and non-responder.
II. To assess the association between single nucleotide polymorphisms that overlap between risk of breast cancer and dense area of breasts; and others that relate to efficiency of tamoxifen metabolism.
III. To evaluate change in breast cancer risk estimates from baseline to 18 months, as assessed by an AI (artificial intelligence) tool and compare changes by dose group.
OUTLINE: This is a within-participant dose-escalation study of tamoxifen.
Participants receive tamoxifen 5mg orally (PO) once daily (QD) for 6 months. Participants with absolute dense area reduction (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.
After completion of study intervention, patients are followed up at 4 weeks.
- Conditions
- Breast Atypical Ductal Hyperplasia, Breast Atypical Lobular Hyperplasia, Breast Carcinoma, Breast Ductal Carcinoma In Situ, Breast Lobular Carcinoma In Situ, Estrogen Receptor-Positive Breast Carcinoma
- Being tested
- Biopsy Procedure, Biospecimen Collection, Mammography, Questionnaire Administration, Tamoxifen
- Medical subject headings
- Carcinoma, Intraductal, Noninfiltrating, Breast Neoplasms, Breast Carcinoma In Situ
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Biopsy ProcedureProcedure or surgery
Also called Biopsy, BIOPSY_TYPE, Bx
Undergo biopsy
Biospecimen CollectionProcedure or surgery
Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo collection of blood samples
MammographyProcedure or surgery
Also called MG
Undergo mammography
Questionnaire AdministrationOther
Ancillary studies
TamoxifenDrug
Also called TMX
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Prevention (tamoxifen) | Experimental | Participants 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. Receives: Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Mammography; Other: Questionnaire Administration; Drug: Tamoxifen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 18 months
Secondary outcomes (5)
Plasma levels of major tamoxifen (TAM) metabolites
Will assess the association of plasma levels of major tamoxifen metabolites with tamoxifen dose and breast density changes from baseline. Metabolite levels will be summarized using standard descriptive statistics at each time point, and change patterns examined using graphical tools for longitudinal data. Will also examine the association of TAM metabolite levels in plasma with aDAR over time using exploratory graphical analyses of aDAR versus (vs.) concurrent metabolite level by time point and dose level. The overall analytic approach to determine whether metabolite levels are associated with aDAR will use linear mixed models.
Measured: At 6, 12, and 18 months
Longitudinal change in serum biomarkers of tamoxifen response
Will evaluate longitudinal change from baseline in serum biomarkers of tamoxifen response at each dose level: sex hormone binding globulin, insulin like growth factor 1 and C-reactive protein. Biomarker values and changes from baseline will be summarized using standard descriptive statistics at each time point by response status. Differences in baseline levels of these biomarkers between different dose sequence groups will be analyzed using linear regression models with biomarker value as the outcome, and dose cohort as the predictor. Will also use linear mixed models to examine biomarker change patterns over time.
Measured: From baseline up to 18 months
Baseline dense area
Will assess the association of baseline dense area (continuous variable) with tamoxifen response. Will be compared using linear regression models between 5 mg responders and non-responders at 6 months, and between dose sequence groups.
Measured: Up to 18 months
Patient-reported symptoms
Will evaluate the impact of tamoxifen dose on participant-reported symptoms using the Breast Eight Symptom Scale. Will examine patient reported outcome (PRO) patterns over time using graphical tools for longitudinal data, and will use descriptive statistics to summarize PRO values at various time points for groups of patients based on their more recent TAM dose level. Changes in PRO from baseline will be summarized similarly. Linear mixed models will be used.
Measured: At baseline, 6, 12, and 18 months
Adherence to final tamoxifen dose
Will evaluate the impact of tamoxifen dose on adherence to final tamoxifen dose. Adherence will be monitored during monthly participant contacts and by pill count and paper diary at each study visit. Will be summarized using descriptive statistics (mean and standard deviation, or median and interquartile range) for each time point and dose level and will be compared between dose levels at each time point using linear regression models. Adverse events will be summarized during each treatment period (0-6, 6-12 and 12-18 months) and dose level, as well as overall for each dose sequence group.
Measured: Up to 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Dec 2023
- Study start27 Sep 2024
- Primary completion31 Mar 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast Atypical Ductal HyperplasiaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Seema A Khan, Principal investigator, Northwestern University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06184750
- Sponsor's protocol ID
- NCI-2023-10628
- Other IDs
- NCI-2023-10628, NCI23-14-01, INT23-14-01, P30CA060553, UG1CA242596, UG1CA242609, UG1CA242632, UG1CA242635
- Status last verified
- Jul 2026
- First submitted
- 27 Dec 2023
- Last updated
- 27 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.