ETHAN - ET for Male BC

NCT05501704 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-225
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 8

Brief Summary

This research study is looking to see how well male breast cancer responds to preoperative treatment with endocrine therapy and which endocrine therapy regimen is the most effective treatment for male breast cancer. The drugs used in this study are:

• Tamoxifen
• Anastrozole
• Degarelix
• Abemaciclib

Conditions

Male Breast Cancer; Hormone Receptor Negative Breast Carcinoma; Hormone Receptor-positive Breast Cancer

Keywords

Male Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Receptor Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Change in Ki-67

  Ki-67 will be evaluated by ImmunoHistoChemistry (IHC) following consensus recommendations using imaging analysis methods.

  At the end of the 3-week window period.

• RCB index

  RCB will be determined using data from each participating institution pathology department, and will be reviewed by the study team pathologist.

  At time of surgery.

Secondary Outcomes (3)

• Changes in estradiol levels

  Baseline and at the end of the three-week window period

• Changes in testosterone levels

  Baseline and at the end of the three-week window period

• Preoperative Endocrine Prognostic Index (PEPI) score

  At time of surgery

Other Outcomes (5)

• Grade 3 or Higher Treatment-Related Toxicity Rate

  Up to 6 months

• Trial enrollment

  3 years

• Trial completion

  3 years

Study Arms (7)

Window Phase Arm A: Tamoxifen

EXPERIMENTAL

Participants will be randomly assigned to receive Tamoxifen 1x daily for 3 weeks (21days).

Drug: Tamoxifen

Window Phase Arm B: Anastrozole

EXPERIMENTAL

Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days).

Drug: Anastrozole

Window Phase Arm C: Anastrozole + Degarelix

EXPERIMENTAL

Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days) and Degarelix on day 1 only.

Drug: Anastrozole; Drug: Degarelix

Neoadjuvant Phase Arm D: Tamoxifen

EXPERIMENTAL

Participants will be randomly assigned to receive Tamoxifen 1x daily for 4 cycles (4 months); each study cycle is 28 days.

Drug: Tamoxifen

Neoadjuvant Phase Arm E: Tamoxifen + Abemaciclib

EXPERIMENTAL

Participants will be randomly assigned to receive Tamoxifen 1x daily and Abemaciclib 2x daily for 4 cycles (4 months); each study cycle is 28 days.

Drug: Tamoxifen; Drug: Abemaciclib

Neoadjuvant Phase Arm F: Anastrozole and Degarelix

EXPERIMENTAL

Participants will be randomly assigned to receive Anastrozole 1x daily and Degarelix on day 1 of each cycle for 4 cycles (4 months); each study cycle is 28 days.

Drug: Anastrozole; Drug: Degarelix

Neoadjuvant Phase Arm G: Anastrozole + Degarelix + Abemaciclib

EXPERIMENTAL

Participants will be randomly assigned to receive Anastrozole 1x daily, Degarelix on day 1 of each cycle and Abemaciclib 2x daily for 4 cycles (4 months); each study cycle is 28 days.

Drug: Anastrozole; Drug: Degarelix; Drug: Abemaciclib

Interventions

Tamoxifen DRUG

Taken orally

Also known as: Nolvadex, Soltamox

Neoadjuvant Phase Arm D: Tamoxifen; Neoadjuvant Phase Arm E: Tamoxifen + Abemaciclib; Window Phase Arm A: Tamoxifen

Anastrozole DRUG

Taken orally

Also known as: Arimidex

Neoadjuvant Phase Arm F: Anastrozole and Degarelix; Neoadjuvant Phase Arm G: Anastrozole + Degarelix + Abemaciclib; Window Phase Arm B: Anastrozole; Window Phase Arm C: Anastrozole + Degarelix

Degarelix DRUG

Subcutaneous (under the skin) injection

Neoadjuvant Phase Arm F: Anastrozole and Degarelix; Neoadjuvant Phase Arm G: Anastrozole + Degarelix + Abemaciclib; Window Phase Arm C: Anastrozole + Degarelix

Abemaciclib DRUG

Taken orally

Also known as: Verzenio

Neoadjuvant Phase Arm E: Tamoxifen + Abemaciclib; Neoadjuvant Phase Arm G: Anastrozole + Degarelix + Abemaciclib

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men aged 18 years or older, with diagnosis of invasive breast cancer who have not undergone surgical resection of the primary tumor and axillary nodes.
• Stage I, II, or III per American Joint Committee on Cancer (AJCC) staging 8th edition (112).
• Breast cancer must be hormone receptor-positive and HER2-negative according to definition below assessed by local pathology.
• Hormone receptor-positive is defined as: positivity for at least one of the hormone receptors (estrogen receptor \[ER\] or progesterone receptor \[PR\]) by IHC. ER and PR assays are considered positive if there are \> 1% positive tumor nuclei in the samples.
• HER2-negative is defined per the current American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline (113).
• Patients with multifocal or multicentric disease are eligible if the treating investigator has determined the patient should be treated as ER-positive and HER2-negative.
• Bilateral breast cancers are allowed if the treating investigator has determined the patient should be treated as ER-positive and HER2-negative.
• Patients with a history of ipsilateral or contralateral DCIS or LCIS are eligible.
• ECOG performance status ≤ 2.
• Required laboratory values demonstrating adequate organ function:
• ANC ≥ 1000/mm3
• Hemoglobin ≥ 8 g/dl
• Platelets ≥ 50,000/mm3
• Serum creatinine ≤ 3.0 x ULN (institutional)
• Total bilirubin ≤ 2.0 x ULN (institutional).

You may not qualify if:

• Prior endocrine therapy, chemotherapy, radiation therapy, or investigational therapy for the current breast cancer diagnosis.
• Prior endocrine therapy, systemic therapy, radiation therapy, or investigational therapy for any other malignancy within the past 12 months.
• Diagnosis of inflammatory breast cancer (T4d).
• Other concurrent serious diseases that may interfere with planned treatment, including severe cardiac disease, congestive heart failure (CHF) of New York Heart Association (NYHA) Class III or higher, severe pulmonary conditions/illness, uncontrolled infections.
• The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment \[e.g. estimated creatinine clearance \<30ml/min\], history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea).
• The patient has active systemic bacterial infection (requiring intravenous \[IV\] antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \[for example, hepatitis B surface antigen positive\]. Screening is not required for enrollment.
• The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.

Sponsors & Collaborators

• Jose Pablo Leone: lead
• Eli Lilly and Company: collaborator
• Translational Breast Cancer Research Consortium (TBCRC): collaborator

Study Sites (8)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

RECRUITING

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Vanderbilt Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

M. D. Anderson Cancer Center at University of Texas

Houston, Texas, 77030-4009, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms, Male

Interventions

Tamoxifen; Anastrozole; acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide; abemaciclib

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Nitriles; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Jose Pablo Leone, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jose Pablo Leone, MD

CONTACT

617-789-2903; josep_leone@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 15, 2022
• Study Start: October 11, 2023
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2036
• Last Updated: April 30, 2026

Record last verified: 2025-12

Data Sharing

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

Locations

US (8)