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ETHAN - ET for Male BC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05501704
Recruitment Status : Recruiting
First Posted : August 15, 2022
Last Update Posted : May 7, 2024
Sponsor:
Collaborators:
Eli Lilly and Company
Translational Breast Cancer Research Consortium (TBCRC)
Information provided by (Responsible Party):
Jose Pablo Leone, Dana-Farber Cancer Institute

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

Condition or disease Intervention/treatment Phase
Male Breast Cancer Hormone Receptor-positive Breast Cancer Hormone Receptor Negative Breast Carcinoma Drug: Tamoxifen Drug: Anastrozole Drug: Degarelix Drug: Abemaciclib Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: ETHAN: A Phase II Study Comparing Different Endocrine THerapies for mAle Breast caNcer
Actual Study Start Date : October 11, 2023
Estimated Primary Completion Date : April 1, 2026
Estimated Study Completion Date : April 1, 2036


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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Arimidex

Drug: Degarelix
Subcutaneous (under the skin) injection

Drug: Abemaciclib
Taken orally
Other Name: Verzenio




Primary Outcome Measures :
  1. Change in Ki-67 [ Time Frame: At the end of the 3-week window period. ]
    Ki-67 will be evaluated by ImmunoHistoChemistry (IHC) following consensus recommendations using imaging analysis methods.

  2. RCB index [ Time Frame: At time of surgery. ]
    RCB will be determined using data from each participating institution pathology department, and will be reviewed by the study team pathologist.


Secondary Outcome Measures :
  1. Changes in estradiol levels [ Time Frame: Baseline and at the end of the three-week window period ]
    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

  2. Changes in testosterone levels [ Time Frame: Baseline and at the end of the three-week window period ]
    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

  3. Preoperative Endocrine Prognostic Index (PEPI) score [ Time Frame: At time of surgery ]
    To evaluate the comparative efficacy of the experimental treatments as measured by PEPI score at surgery.


Other Outcome Measures:
  1. Grade 3 or Higher Treatment-Related Toxicity Rate [ Time Frame: Up to 6 months ]
    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.

  2. Trial enrollment [ Time Frame: 3 years ]
    We will evaluate how many patients we are able to enroll to this trial in a period of 3 years

  3. Trial completion [ Time Frame: 3 years ]
    We will evaluate how many of the enrolled participants successfully complete the study protocol

  4. EORTC QLC-C30 questionnaire [ Time Frame: Up to 6 months ]
    Patient-reported outcomes (PROs) measures will be conducted using the EORTC QLC-C30 questionnaire.

  5. Adapted EORTC BR23 questionnaire [ Time Frame: Up to 6 months ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05501704


Contacts
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Contact: Jose Pablo Leone, MD 617-789-2903 josep_leone@dfci.harvard.edu

Locations
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United States, District of Columbia
Georgetown University Medical Center Not yet recruiting
Washington, District of Columbia, United States, 20007
Contact: Clinical Trials Office Breast Cancer    202-444-2223      
Principal Investigator: Elaine Walsh, MD         
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jose Pablo Leone, MD    617-789-2903      
Principal Investigator: Jose Pablo Leone, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Cancer Trials Referral Office    855-776-0015      
Principal Investigator: Kathryn Ruddy, MD         
United States, Texas
M. D. Anderson Cancer Center at University of Texas Recruiting
Houston, Texas, United States, 77030-4009
Contact: Clinical Trials Office - M. D. Anderson Cancer Center at the U    713-792-3245      
Principal Investigator: Jasmine Sukumar, M.D         
Sponsors and Collaborators
Jose Pablo Leone
Eli Lilly and Company
Translational Breast Cancer Research Consortium (TBCRC)
Investigators
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Principal Investigator: Jose Pablo Leone, MD Dana-Farber Cancer Institute
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Responsible Party: Jose Pablo Leone, Principal Investigator, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT05501704    
Other Study ID Numbers: 22-225
First Posted: August 15, 2022    Key Record Dates
Last Update Posted: May 7, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (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

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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
Keywords provided by Jose Pablo Leone, Dana-Farber Cancer Institute:
Male Breast Cancer
Hormone Receptor-positive Breast Cancer
Hormone Receptor Negative Breast Cancer
Additional relevant MeSH terms:
Layout table for MeSH terms
Breast Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Tamoxifen
Anastrozole
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Bone Density Conservation Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action