Refining Tamoxifen Dose for Premenopausal Breast Cancer Risk Reduction (RENAISSANCE): A Phase II Single Arm Trial

Status: Recruiting
Location: See all (11) locations...
Intervention Type: Procedure, Other, Drug
Study Type: Interventional
Study Phase: Phase 2
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.

Eligibility
Participation Requirements
Sex: Female
Minimum Age: 18
Maximum Age: 55
Healthy Volunteers: f
View:

• 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

• 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 oral contraceptive preparation throughout the duration of the trial. For women who have a levonorgestrel-coated intra-uterine device, removal for medical reasons will be 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) 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 (BIRAD) 1 or 2. If BIRAD 0, follow-up diagnostic imaging must be BIRAD 1 or 2 or cleared clinically with radiology recommendation of return to annual screening

• Women who are factor V leiden carriers and have not had a blood clot are eligible, if approved by their treating physician

Locations
United States
Arizona
University of Arizona Cancer Center - Prevention Research Clinic
RECRUITING
Tucson
Illinois
Northwestern University
RECRUITING
Chicago
University of Illinois College of Medicine - Chicago
RECRUITING
Chicago
Kansas
University of Kansas Cancer Center
RECRUITING
Kansas City
Massachusetts
Brigham and Women's Hospital
RECRUITING
Boston
Dana-Farber Cancer Institute
RECRUITING
Boston
Michigan
University of Michigan Comprehensive Cancer Center
RECRUITING
Ann Arbor
Missouri
Washington University School of Medicine
RECRUITING
St Louis
Ohio
Case Western Reserve University
NOT_YET_RECRUITING
Cleveland
South Carolina
Medical University of South Carolina
RECRUITING
Charleston
Texas
M D Anderson Cancer Center
RECRUITING
Houston
Time Frame
Start Date: 2024-09-27
Estimated Completion Date: 2028-09-30
Participants
Target number of participants: 200
Treatments
Experimental: Prevention (tamoxifen)
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.
Related Therapeutic Areas
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov