Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer

NCT07499999 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-550
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this research study is to evaluate the efficacy and safety of low-dose exemestane versus low-dose tamoxifen in post-menopausal women at high risk for breast cancer. The names of the study drugs involved in this study are:

• Exemestane (a type of steroidal aromatase inhibitor)
• Tamoxifen (a type of selective estrogen receptor modulator)

Conditions

Breast Cancer; Ductal Carcinoma; Estrogen-receptor-positive Breast Cancer; Atypical Lobular Hyperplasia; BRCA2 Mutation; CHEK2 Gene Mutation; Ataxia Telangiectasia Mutated Gene Mutation

Keywords

Breast Cancer; High Risk Breast Cancer; Cancer Prevention; Ductual Carcinoma in Site; Estrogen Receptor Positive; High Risk Lesions; HRL; Atypical Lobular Hyperplasia; BRCA2; CHEK2; ATM

Outcome Measures

Primary Outcomes (1)

• Difference in Overall Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) Between the Two Arms at 12 Months

  The MENQOL assesses the degree to which menopausal symptoms are troublesome in four domains: vasomotor (three items), sexual (three items), physical (seven items), and psychosocial (16 items). Each item is answered with Yes or No. If the response is Yes, the participant rates how bothersome the symptom was on a scale from 0 to 6, where 0 indicates "not at all bothered" and 6 indicates "extremely bothered." For each participant, the difference between the baseline and 12-month overall MENQOL score will be calculated and defined as the "change."

  12 Months

Secondary Outcomes (21)

• Difference of Free Estradiol Levels between Two Arms at 12 Months

  12 Months

• Difference of Estradiol/Sex Hormone Binding Globulin (SHBG) Levels between Two Arms at 12 Months

  12 Months

• Difference of Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Levels Between Two Arms at 12 Months

  12 Months

• Insulin-like Growth Factor I (IGF-I)/Insulin-like Growth Factor Binding Protein 3 (IGFBP-3) Ratio Between Two Arms at 12 Months

  12 Months

• Overall Domain Score Change From Baseline in Menopause-Specific Quality of Life Questionnaire (MENQOL) at 6 Months

  6 months

Study Arms (2)

Low-Dose Exemestane

EXPERIMENTAL

Participants will be randomized 1:1 with a permuted-block technique and stratified by center and will complete: * Baseline visit with assessments * Predetermined dose of Exemestane 1x on every odd day for 12 months * 3 month in-clinic visit * 6 month in-clinic visit * 9 month in-clinic visit * 12 month end of intervention in-clinic visit * Follow up for 12 months

Drug: Exemestane

Low-Dose Tamoxifen

EXPERIMENTAL

Participants will be randomized 1:1 with a permuted-block technique and stratified by center and will complete: * Baseline visit with assessments * Predetermined dose of Tamoxifen 1x on every odd day for 12 months * 3 month in-clinic visit * 6 month in-clinic visit * 9 month in-clinic visit * 12 month end of intervention in-clinic visit * Follow up for 12 months

Drug: Tamoxifen

Interventions

Exemestane DRUG

A steroidal aromatase inhibitor, blinded capsules taken orally, per protocol.

Also known as: C20H24O2

Low-Dose Exemestane

Tamoxifen DRUG

A selective estrogen receptor modulator, blinded capsules taken orally, per protocol.

Also known as: C32H37NO8

Low-Dose Tamoxifen

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Postmenopausal state is defined⁸ as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy.
• Any of the following criteria must be met:
• Recent (within 12 months from date of consent form signature) histologic diagnosis of ER+ve (\>5%) DCIS (patients with DCIS should have undergone breast-conserving therapy i.e. lumpectomy to remove the tumor with negative surgical margins followed by radiotherapy (see footnote 1 below)) diagnosis within 3 years of HRL (ADH, LCIS, ALH), or;
• At least 3% breast cancer risk at 5 years (or 5% risk at 10yrs) per one of the following risk models: the Breast Cancer Surveillance Consortium risk calculator V3 or Tyrer-Cuzick model V8 or;
• Known carriers of a germline pathogenic/likely pathogenetic variant in the following moderate penetrance genes (CHEK2 or ATM), or women with chest wall irradiation before age of 30 years
• Eastern Cooperative Oncology Group - Performance Status (ECOG-PS) 0-1
• Able to swallow oral medications
• Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Specifically, all cancers diagnosed since 3 years or longer except for breast and endometrial are eligible.
• Ability to understand and the willingness to sign a written informed consent document
• Mammography performed up to 6 months before the trial consent form signature
• DEXA performed up to 12 months before the trial consent form signature
• Life expectancy ≥ 10 years
• Normal liver function tests and blood cell count
• Negative gynecological examination performed up to 6 months before the trial consent form signature.
• ᶥ While DCIS and ADH are routinely excised, and treatment of DCIS often includes radiotherapy, lobular neoplasia (ALH and classic LCIS) are not routinely excised in most US centers unless radiologic-pathologic findings are discordant given the very low risk of an associated cancer.11,12 Participants with DCIS should have undergone breast-conserving therapy i.e. lumpectomy to remove the tumor with negative surgical margins followed by radiotherapy. All DCIS will require excision to clear margins per the SSO/ASCO/ASTRO margin guidelines for DCIS.88 In selected cases, the decision to omit RT might be taken according to low risk clinical-pathological factors (e.g., age\>70, low grade, size \< 1 cm, and genomic assays if available) as well as patient preference after full discussion of the risks and benefits.

You may not qualify if:

• Pre/perimenopausal women: exemestane is only effective in post-menopausal women
• History of DVT or PE: tamoxifen can increase tendency to blood clot
• Endometrial cancer: full-dose tamoxifen is associated with increased risk of endometrial cancers
• Macular disorders: tamoxifen is associated with retinal damage
• Inability to comply with study procedures: standard
• Prior use of antiestrogens within 12 months from the date of the trial consent form signature: there can be long duration effects from antiestrogens that could influence trial drug effects
• Use of hormone replacement therapy (HRT) within 3 months from the date of the trial consent form signature: similarly, wish to avoid any long lasting effect before alternate effect from study drugs
• Severe osteoporosis (T score ≤ 2.5 at either spine or hip), or recent vertebral fracture (within 6 months) not treated with zoledronic acid or denosumab: Exemestane is an aromatase inhibitor which can worsen bone loss (osteoporosis)
• Current use of terbinafine, quinidine, cinacalcet, rifampicin, phenytoin, carbamazepine, phenobarbital, St. John's wort, warfarin, erythromycin, cyclosporin, nifedipine and any concomitant coumarin-type anti-coagulant therapy: these drugs compete for the Cytochrome P450 metabolic pathways of tamoxifen and exemestane
• Moderate or severe renal impairment: Exemestane is eliminated equally by liver and renal metabolism
• Known hypersensitivity to study drugs: standard
• Screening Eligibility Criteria
• To register a participant to the screening phase, the following documents should be provided by the participating site:
• Signed participant consent form
• Postmenopausal status, and any of the following:

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Breast Cancer Research Foundation: collaborator

Study Sites (2)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Ductal

Interventions

exemestane; Tamoxifen

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Judy Garber, MD. MPH

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Judy Garber, MD, MPH

CONTACT

617-632-2282; judy_garber@dfciharvard.edu

Judy Garber, MD. MPH

CONTACT

617-582-8321; judy_garber@dfciharvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 24, 2026
• First Posted: March 30, 2026
• Study Start (Estimated): September 9, 2026
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2028
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: DFCI- Contact the Belfer office for Dana -Farber Innovations (BODFI) at innovations@dfci.harvard.edu

Locations

US (2)