Hormone Therapy for Male Breast Cancer

Recruiting at 8 trial locations

Overseen By Jose Pablo Leone, MD

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: Jose Pablo Leone

Disqualifiers: Inflammatory breast cancer, severe cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 7

Duration: 4 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of different hormone therapies for male breast cancer before surgery. The study compares several treatments, including Tamoxifen, Anastrozole, Degarelix, and Abemaciclib, to determine which is most effective. It targets men with hormone receptor-positive and HER2-negative breast cancer that has not yet been surgically removed. Participants should be able to take oral medications and be willing to undergo a biopsy after the initial treatment phase. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to significant advancements in cancer treatment.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you have been on any endocrine therapy, chemotherapy, or radiation therapy for breast cancer or any other cancer in the past 12 months, you would not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatments in this study have been tested in people before, with varying side effects.

Tamoxifen is usually well-tolerated by men, though some report side effects like weight gain and sexual problems. In one study, about half of the male breast cancer patients experienced these issues. However, most men continue the treatment successfully.

Anastrozole has also shown some side effects. Previous studies found that around 37.5% of patients reported reduced interest in sex, leg swelling, and depression. Despite this, it remains safe and effective for hormone-sensitive breast cancer.

Degarelix is typically used for prostate cancer. While it can cause infertility in male animals, human studies haven't linked it to serious problems. Common side effects include hot flashes and injection site reactions, such as redness or swelling.

Abemaciclib has been tested on many breast cancer patients. It can cause diarrhea and low white blood cell counts, but these are manageable with proper care.

Overall, these treatments have been used for other conditions and are generally safe, though side effects can occur. It's important to discuss any concerns or symptoms with the study team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for male breast cancer because they explore new combinations of hormone therapy that could improve outcomes. Unlike standard options like Tamoxifen alone, these treatments combine it with Abemaciclib, a CDK4/6 inhibitor, which may enhance the drug's effectiveness by targeting cancer cell growth more directly. Another combination of Anastrozole and Degarelix offers hormone suppression from different angles, potentially providing a more comprehensive approach to halting cancer progression. These unique combinations aim to offer more potent and targeted intervention compared to current therapies.

What evidence suggests that this trial's treatments could be effective for male breast cancer?

Studies have shown that tamoxifen, one of the treatments in this trial, effectively treats male breast cancer, with about 37.5% of advanced cases showing improvement. Research suggests that anastrozole, another treatment option in this trial, may also benefit men, with patients experiencing an average of 4.4 months without disease progression and an overall survival time of 33 months. Degarelix, also under study in this trial, has proven effective for hormone-sensitive conditions, though specific data on male breast cancer remains limited. For abemaciclib, included in some treatment arms of this trial, studies in men indicate it can combat cancer, even in advanced stages, and improve survival when combined with other treatments. These findings suggest that each treatment can be beneficial, but effectiveness may vary based on individual circumstances. ^{6 7 8 9 10}

Who Is on the Research Team?

Jose Pablo Leone, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for men aged 18+ with invasive breast cancer that's hormone receptor-positive and HER2-negative, who haven't had surgery yet. Participants must be able to take oral meds, have certain organ function levels, and use contraception if with a partner of childbearing potential. Excluded are those with serious medical conditions, active infections, inflammatory breast cancer or recent treatments for other cancers.

Inclusion Criteria

I can take pills by mouth.

I am willing to have a breast biopsy after the initial treatment phase.

I have had ductal or lobular carcinoma in situ in either breast.

Exclusion Criteria

I currently have an active infection (bacterial, fungal, or viral).

The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study

I have been diagnosed with inflammatory breast cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Window Phase

Participants receive endocrine therapy for 3 weeks to evaluate initial response

3 weeks

1 visit (in-person)

Treatment

Participants receive one of four endocrine therapy treatment combinations for 4 months

4 months

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

2 visits (in-person)

Long-term Follow-up

Participants are followed for up to 10 years to monitor long-term outcomes

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Abemaciclib
• Anastrozole
• Degarelix
• Tamoxifen

Trial Overview The ETHAN study tests how male breast cancer responds to preoperative endocrine therapy. It compares the effectiveness of Tamoxifen, Anastrozole, Degarelix, and Abemaciclib in treating this condition before surgery.

How Is the Trial Designed?

Group I: Window Phase Arm C: Anastrozole + Degarelix Experimental Treatment 2 Interventions

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

Group II: Window Phase Arm B: Anastrozole Experimental Treatment 1 Intervention

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

Group III: Window Phase Arm A: Tamoxifen Experimental Treatment 1 Intervention

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

Group IV: Neoadjuvant Phase Arm G: Anastrozole + Degarelix + Abemaciclib Experimental Treatment 3 Interventions

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.

Group V: Neoadjuvant Phase Arm F: Anastrozole and Degarelix Experimental Treatment 2 Interventions

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.

Group VI: Neoadjuvant Phase Arm E: Tamoxifen + Abemaciclib Experimental Treatment 2 Interventions

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.

Group VII: Neoadjuvant Phase Arm D: Tamoxifen Experimental Treatment 1 Intervention

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

Abemaciclib is already approved in United States, European Union for the following indications:

Approved in United States as Verzenio for:

• Hormone receptor-positive (HR+), human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Approved in European Union as Verzenio for:

• HR+, HER2- advanced or metastatic breast cancer
• HR+, HER2- node-positive early breast cancer

Who Is Running the Clinical Trial?

Jose Pablo Leone

Lead Sponsor

Trials

1

Recruited

60+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Translational Breast Cancer Research Consortium (TBCRC)

Collaborator

Trials

1

Recruited

60+

Published Research Related to This Trial

Male breast cancer is rare in Europe, with an incidence of 1 or less per 100,000, and typically peaks at age 71, highlighting the need for awareness and research in this area.

The preferred treatment for male breast cancer includes modified radical mastectomy and routine post-operative radiotherapy, with tamoxifen being the main adjuvant therapy for hormone-responsive cases, although the use of aromatase inhibitors remains debated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to treat male breast cancer. Czene, K., Bergqvist, J., Hall, P., et al.[2019]

Male breast cancer (MBC) is becoming more common in the U.S., but mortality rates have not improved, highlighting a need for better understanding and treatment strategies specific to MBC.

Current treatments for MBC, primarily hormonal therapies like tamoxifen, are often based on female breast cancer protocols, despite significant biological differences between the two, suggesting that tailored approaches are necessary for effective management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy for male breast cancer: A different approach for a different disease. Nahleh, ZA.[2022]

Male breast cancer is rare, occurring at about 1% of the rate of female breast cancer, and is often highly positive for hormone receptors, making hormone therapy the primary treatment.

For advanced cases, treatments like tamoxifen and orchiectomy are common, while newer hormonal therapies show promise but require further study to confirm their effectiveness in male breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for male breast cancer. Hayes, T.[2019]

Men with breast cancer should undergo mastectomy as the primary surgical treatment, and decisions regarding additional systemic treatments should be based on factors similar to those used for women, including tumor size and hormone receptor status.

Hormonal therapy is crucial for treating hormone receptor-positive breast cancer in men, with tamoxifen as the first-line treatment, while newer aromatase inhibitors may also be effective, and options like orchiectomy or LHRH agonists are available for second-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Male breast cancer. Volm, MD.[2022]

In a study involving 21 men with prostate cancer, the use of tamoxifen or anastrozole did not significantly affect the plasma concentrations of bicalutamide, suggesting that these antiestrogens can be safely used without altering the effectiveness of bicalutamide treatment.

While the study indicates no major impact on bicalutamide levels, the small sample size means that further research is necessary to fully understand any potential interactions and their implications for prostate cancer management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exploratory study of drug plasma levels during bicalutamide 150 mg therapy co-administered with tamoxifen or anastrozole for prophylaxis of gynecomastia and breast pain in men with prostate cancer. Boccardo, F., Rubagotti, A., Conti, G., et al.[2018]

Bicalutamide, an androgen receptor antagonist approved for treating locally advanced prostate cancer, is associated with significant breast-related side effects, affecting nearly 90% of patients, leading to withdrawal in about 16% of cases.

Tamoxifen has shown promise as the most effective treatment for managing these breast events, but further research is needed to optimize its use and understand its impact on prostate cancer control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of bicalutamide-induced breast events. Sieber, PR.[2014]

In a case study of a male patient with ER+ and Her2+ advanced breast cancer, treatment with trastuzumab and anastrozole resulted in 11 months of progression-free survival without any adverse events.

This suggests that the combination of trastuzumab and anastrozole may be a safe and effective treatment option for men with this type of breast cancer, although more research is needed to establish optimal hormonal therapies in this rare population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential benefit of maintenance trastuzumab and anastrozole therapy in male advanced breast cancer. Carmona-Bayonas, A.[2018]

A male patient with metastatic breast cancer showed a clinical response to treatment with letrozole, an aromatase inhibitor, indicating its potential effectiveness in male breast cancer cases.

The treatment led to a significant decrease in blood oestradiol levels, suggesting that aromatase inhibitors may be a promising therapeutic option for hormone receptor-positive breast cancer in men.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aromatase inhibitors and male breast cancer. Arriola, E., Hui, E., Dowsett, M., et al.[2019]

There is limited information on the optimal treatment for male breast cancer due to its low incidence, with no prospective randomized trials available, making it difficult to extrapolate treatment recommendations from female breast cancer studies.

Current standard treatment involves tamoxifen, which is preferred for its low side effects, but its effectiveness compared to orchiectomy is unknown; further research is needed to explore the efficacy of other therapies like aromatase inhibitors and GnRH-analogs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Systemic therapy of male breast cancer]. Eucker, J., Kühnl, A., Possinger, K.[2018]

In a study of 24 male breast cancer patients treated with adjuvant tamoxifen, 62.5% reported at least one side effect, with decreased libido being the most common (29.2%).

The attrition rate for male patients due to side effects was significantly higher at 20.8%, compared to only 4% in female patients, indicating that male breast cancer patients may experience more severe side effects from tamoxifen treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tamoxifen administration is associated with a high rate of treatment-limiting symptoms in male breast cancer patients. Anelli, TF., Anelli, A., Tran, KN., et al.[2022]

A study comparing 49 male breast cancer patients to 680 postmenopausal female patients found that while male tumors were generally smaller at diagnosis, both groups had similar survival outcomes and prognostic factors, indicating comparable disease characteristics.

However, male patients experienced a higher drop-out rate from adjuvant endocrine therapy (16.3% vs. 7.6% in females), primarily due to side effects, highlighting a need for better management of treatment tolerability in male breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical, Pathological, and Prognostic Features of Male Breast Cancer: A Multicenter Study. Accomasso, F., Actis, S., Minella, C., et al.[2023]

A 28-year-old man with metastatic androgen receptor (AR)+ and estrogen receptor (ER)+ breast cancer showed a durable clinical response to hormonal suppression using a combination of Letrozole (an aromatase inhibitor) and Leuprolide (a GnRH agonist).

This case highlights the potential effectiveness of hormonal therapies in treating male breast cancer, which is less understood compared to female breast cancer, particularly regarding the role of androgen receptors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A role for the androgen receptor in the treatment of male breast cancer. Zhu, J., Davis, CT., Silberman, S., et al.[2016]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10129913/

Characteristics and Outcomes in Cases of US Male ... Most male patients received an abemaciclib-containing regimen in ≥ 3L, with anti-cancer activity observed despite heavy metastatic burden and prior treatments ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625006149

Metastatic Breast Cancer: A Propensity-Matched ... In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04031885

NCT04031885 | A Study of Abemaciclib (LY2835219) in ... The reason for this study is to compare the efficacy of abemaciclib, in combination with fulvestrant, to that of physician's choice of chemotherapy in women ...

4. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK601722/

Clinical Review - Abemaciclib (Verzenio) - NCBI Bookshelf - NIH Based on data from the monarchE trial, abemaciclib plus ET demonstrated a statistically significant and clinically meaningful benefit compared to ET ...

5. prnewswire.com prnewswire.com/news-releases/lillys-verzenio-abemaciclib-prolonged-survival-in-hr-her2--high-risk-early-breast-cancer-with-two-years-of-treatment-302586849.html

Lilly's Verzenio® (abemaciclib) prolonged survival in HR+, ... In the intent-to-treat (ITT) population, Verzenio plus ET reduced the risk of death by 15.8% compared to ET alone [7-year overall survival (OS) ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/208716s006s007s008lbl.pdf

VERZENIO® (abemaciclib) tablets, for oral use The data described below reflect exposure to VERZENIO in 441 patients with. HR-positive, HER2-negative advanced breast cancer who received at least one dose of ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/abemaciclib-oral-route/description/drg-20406567

Abemaciclib (oral route) - Side effects & dosage Abemaciclib belongs to the group of medicines called antineoplastics. It interferes with the growth of cancer cells, which are eventually ...

8. oncologynewscentral.com oncologynewscentral.com/drugs/monograph/174190-317058/abemaciclib-oral

Abemaciclib: uses, dosing, warnings, adverse events, ... Abemaciclib is used in combination with fulvestrant for the treatment of hormone receptor-positive, HER2-negative advanced or metastatic breast cancer in adults ...

9. ema.europa.eu ema.europa.eu/en/documents/product-information/verzenios-epar-product-information_en.pdf

Verzenios, INN-abemaciclib - European Medicines Agency There are no data on the efficacy and safety of abemaciclib in patients with visceral crisis. ... breast cancer cell lines, sustained target inhibition with ...

10. verzenio.lilly.com verzenio.lilly.com/

Early and Metastatic Breast Cancer Treatment | Verzenio® ... Verzenio (abemaciclib) is a treatment for both HR+, HER2-, high risk, node positive early breast cancer and for certain types of HR+, HER2- metastatic ...