ETHAN - ET for Male BC

ETHAN: A Phase II Study Comparing Different Endocrine THerapies for mAle Breast caNcer

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

Study Overview

• Status: Recruiting
• Conditions: Male Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Receptor Negative Breast Carcinoma
• Intervention / Treatment: Drug: Tamoxifen; Drug: Anastrozole; Drug: Degarelix; Drug: Abemaciclib

Detailed Description

This is an open-label, multicenter, randomized trial for men with stage I-III hormone receptor-positive (HR+)/HER2-negative breast cancer. The trial will have two phases: A 3-week window phase containing endocrine therapy followed by a 4-month treatment phase where participants are treated with one of four endocrine therapy treatment combinations.

Tamoxifen is the standard of care for the treatment of breast cancer in men. Anastrozole is a standard treatment in women with breast cancer and works more effectively than tamoxifen. This study hopes to learn if anastrozole may also be effective in men. Given that gonadal suppression and CDK 4/6 inhibitors have both improved treatment in women with breast cancer, the study hopes to learn how the addition of Degarelix (gonadal suppression) and Abemaciclib (CDK 4/6 inhibitors) work in comparison to standard of care tamoxifen.

The research study procedures include screening for eligibility and study treatment including laboratory evaluations and quality of life questionnaires.

After completion of treatment, participants will be followed for up to 10 years

It is expected that about 60 men will take part in this research study.

Eli Lilly, a pharmaceutical company, is supporting this research study by providing one of the study drugs. This study is also being supported by Johns Hopkins University on behalf of the Translational Breast Cancer Research Consortium (TBCRC).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jose Pablo Leone, MD; Phone Number: 617-789-2903; Email: josep_leone@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana Farber Cancer Institute
      • Contact: Jose Pablo Leone, MD; Phone Number: 617-789-2903
      • Principal Investigator: Jose Pablo Leone, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Contact: Cancer Trials Referral Office; Phone Number: 855-776-0015
      • Principal Investigator: Kathryn Ruddy, MD
  • Texas
    • Houston, Texas, United States, 77030-4009
      • Recruiting
      • M. D. Anderson Cancer Center at University of Texas
      • Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U; Phone Number: 713-792-3245
      • Principal Investigator: Jasmine Sukumar, M.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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).
  • AST and ALT ≤ 5.0 x ULN (institutional)
• Men with partners of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 6 months after the last dose of study treatment.
• Non-English-speaking patients are eligible but will be exempt from patient-completed questionnaires.
• Willing and able to sign informed consent.
• Willing to undergo breast biopsy after completion of window phase.
• Patient is able to swallow oral medications.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Window Phase Arm A: Tamoxifen; Participants will be randomly assigned to receive Tamoxifen 1x daily for 3 weeks (21days).	Drug: Tamoxifen; Taken orally; Other Names: Nolvadex; Soltamox
Experimental: Window Phase Arm B: Anastrozole; Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days).	Drug: Anastrozole; Taken orally; Other Names: Arimidex
Experimental: Window Phase Arm C: Anastrozole + Degarelix; Participants will be randomly assigned to receive Anastrozole 1x daily for 3 weeks (21days) and Degarelix on day 1 only.	Drug: Anastrozole; Taken orally; Other Names: Arimidex; Drug: Degarelix; Subcutaneous (under the skin) injection
Experimental: Neoadjuvant Phase Arm D: Tamoxifen; Participants will be randomly assigned to receive Tamoxifen 1x daily for 4 cycles (4 months); each study cycle is 28 days.	Drug: Tamoxifen; Taken orally; Other Names: Nolvadex; Soltamox
Experimental: Neoadjuvant Phase Arm E: Tamoxifen + Abemaciclib; 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; Taken orally; Other Names: Nolvadex; Soltamox; Drug: Abemaciclib; Taken orally; Other Names: Verzenio
Experimental: Neoadjuvant Phase Arm F: Anastrozole and Degarelix; 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; Taken orally; Other Names: Arimidex; Drug: Degarelix; Subcutaneous (under the skin) injection
Experimental: Neoadjuvant Phase Arm G: Anastrozole + Degarelix + Abemaciclib; 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; Taken orally; Other Names: Arimidex; Drug: Degarelix; Subcutaneous (under the skin) injection; Drug: Abemaciclib; Taken orally; Other Names: Verzenio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in estradiol levels	To evaluate the physiologic endocrine changes that occur as a result of treatment with tamoxifen, anastrozole and anastrozole and degarelix as measured by estradiol levels at baseline and at the end of the three-week window period	Baseline and at the end of the three-week window period
Changes in testosterone levels	To evaluate the physiologic endocrine changes that occur as a result of treatment with tamoxifen, anastrozole and anastrozole and degarelix as measured by testosterone levels at baseline and at the end of the three-week window period	Baseline and at the end of the three-week window period
Preoperative Endocrine Prognostic Index (PEPI) score	To evaluate the comparative efficacy of the experimental treatments as measured by PEPI score at surgery.	At time of surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade 3 or Higher Treatment-Related Toxicity Rate	All grade 3 or higher adverse events (AE) with treatment attribution of possibly, probably or definite based on CTCAEv5 as reported on case report forms were counted. Rate is the proportion of treated participants experiencing at least one treatment-related grade 3 or higher AE of any type during the time of observation.	Up to 6 months
Trial enrollment	We will evaluate how many patients we are able to enroll to this trial in a period of 3 years	3 years
Trial completion	We will evaluate how many of the enrolled participants successfully complete the study protocol	3 years
EORTC QLC-C30 questionnaire	Patient-reported outcomes (PROs) measures will be conducted using the EORTC QLC-C30 questionnaire.	Up to 6 months
Adapted EORTC BR23 questionnaire	Patient-reported outcomes (PROs) measures will be conducted using the EORTC BR23, adapted by replacing female-specific items with male-specific sexual activity/function items from PR25 (Appendix D of protocol) questionnaire.	Up to 6 months

Collaborators and Investigators

• Sponsor: Jose Pablo Leone
• Collaborators: Eli Lilly and Company; Translational Breast Cancer Research Consortium (TBCRC)
• Investigators: Principal Investigator: Jose Pablo Leone, MD, Dana-Farber Cancer Institute

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2023
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2036

Study Registration Dates

• First Submitted: August 10, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 15, 2022

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 2, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Male Breast Cancer; Hormone Receptor-positive Breast Cancer; Hormone Receptor Negative Breast Cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Breast Neoplasms, Male; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Bone Density Conservation Agents; Aromatase Inhibitors; Steroid Synthesis Inhibitors; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Tamoxifen; Anastrozole
• Other Study ID Numbers: 22-225

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No