Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Carcinoma

Breast Neoplasms

Breast Neoplasms, Male

Breast Diseases

Skin Diseases

Breast Cancer, Male

Bone Density Conservation Agents

Antineoplastic Agents

All Drugs and Chemicals

Tamoxifen

Hormones

Anastrozole

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

Estrogen Receptor Modulators

Selective Estrogen Receptor Modulators

Aromatase Inhibitors

Enzyme Inhibitors

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

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

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

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

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.

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.

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.

Degarelix

Abemaciclib

Jose Pablo Leone, MD

Clinical Trials Office Breast Cancer

Elaine Walsh, MD

Cancer Trials Referral Office

Kathryn Ruddy, MD

Clinical Trials Office - M. D. Anderson Cancer Center at the U

Jasmine Sukumar, M.D

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

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).

ETHAN - ET for Male BC

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

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.

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.

We will evaluate how many patients we are able to enroll to this trial in a period of 3 years

We will evaluate how many of the enrolled participants successfully complete the study protocol

Patient-reported outcomes (PROs) measures will be conducted using the EORTC QLC-C30 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.

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

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

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

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

To evaluate the comparative efficacy of the experimental treatments as measured by PEPI score at surgery.

Eli Lilly and Company

Translational Breast Cancer Research Consortium (TBCRC)

Jose Pablo Leone

Principal Investigator

Symptoms and General Pathology

Neoplasm Metastasis

Triple Negative Breast Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Amino Acids

Antibodies

Antibodies, Monoclonal

Trastuzumab

Trastuzumab deruxtecan

Immunoglobulins

Immunoglobulin G

Mitogens

Tyrosine Kinase Inhibitors

Immunoglobulins, Intravenous

Tucatinib

Topoisomerase I Inhibitors

Antineoplastic Agents, Immunological

Immunoconjugates

Immunologic Factors

Protein Kinase Inhibitors

Tyrosine

The combination of T-DXd and ALX148 aims to explore the anti-tumoral effects of trastuzumab, of the topoisomerase inhibitor DXd and of the CD47-blocking agent ALX148. The rationale for this combination is that ALX148 is hypothesized, based on preclinical data, to facilitate antibody-dependent cellular phagocytosis (ADCP) of HER2 expressing (\>HER2 1+) breast cancer binding T-DXd while cancer cell intrinsic or bystander cytotoxicity of T-DXd will result in the release of neoantigens promoting immune mediated antitumor activity in the tumor microenvironment.

Zanidatamab is a bispecific IgG1-like antibody directed against two distinct HER2 epitopes. It induces formation of receptor clusters and internalization resulting in downregulation. It also inhibits growth factor-dependent and -independent tumor cell proliferation as well as potently activating ADCC, ADCP, and CDC.

Tucatinib is a highly selective, small molecule tyrosine kinase inhibitor (TKI) of HER2 compared to other TKI's (i.e., EGFR). It is well tolerated, crosses the blood brain barrier and can treat CNS disease. It is FDA approved for HER2+ breast cancer.

Given the promising clinical data for each of these drugs which have different mechanisms, the effect of zanidatamab after T-DXd (Enhertu®) in breast cancer patients, and the favorable toxicity profile of both drugs, we hypothesize that the combination of tucatinib and zanidatamab will be well tolerated and more efficacious than either drug alone for the treatment of patients with HER2 positive breast cancer.

CD47 Inhibitor: A fusion protein containing a high affinity engineered D1 domain of human signal regulatory protein alpha (SIRPα) variant 1 (v1) genetically linked to a modified and inactive Fc domain of human immunoglobulin (Ig) G1.

ALX148

Antibody-drug conjugate (ADC): A recombinant humanized anti-human HER2 IgG1 monoclonal antibody, conjugated with linker to a Topoisomerase I inhibitor

Fam-Trastuzumab Deruxtecan-Nxki

Bispecific HER2 antibody: A humanized, bispecific, immunoglobulin G isotype 1 (IgG1)-like antibody directed against the juxtamembrane extracellular domain (ECD4) and the dimerization domain (ECD2) of human epidermal growth factor receptor 2 (HER2).

Zanidatamab

Small molecule tyrosine kinase inhibitor (TKI) of HER2 (oral drug).

Smita M Asare

Maria Pitsiouni, PhD

Clara Duarte

Yordanos Tafesse

Nan Chen, MD

Rita Nanda, MD

Katie Vaughn, RN

Jessica Hellmer

David Potter, MD, PhD

Doug Yee, MD

Heather Walker

Julia Moore, RN

Paula Pohlmann, MD, MSc, PhD

Debasish Tripathy, MD

Paula R Pohlmann, MD, MSc, PhD

I-SPY Phase I/Ib (I-SPY-P1) is an open-label, multisite platform study designed to evaluate single agents or combinations in a metastatic treatment setting that may be relevant for breast cancer patients with the overall goal of moving promising drug regimens into the I-SPY 2 SMART Design Trial (NCT01042379) and/or other oncology-based trials in a timely manner.

The PRE-I-SPY/I-SPY-P1 study is a platform trial with multiple ongoing drug regimen arms. In most cases, the treatment arm will have a dose-finding group (Part 1) and a dose-expansion group (Part 2). Eligibility criteria will vary according to the experimental regimen. Participant eligibility may vary according to the arm or the part within the study arm, including with respect to diagnosis. Arms could include participants diagnosed with certain solid tumors or specifically with breast cancer. Arms may restrict enrollment to a certain molecular pathway abnormality or histologic diagnosis. The trial allows for various study arm designs, with the goal to complete analysis of a study arm in 12 to 18 months.

This is an open-label, multi-site, multi-arm platform study, where each drug regimen arm may have different study designs and eligibility. In particular, dose finding parts may employ different designs (e.g., 3+3, Bayesian Optimal Interval Design \[BOIN\], continual reassessment method \[CRM\], etc.) for each arm in the PRE-I-SPY program. See each arm for specific study model details.

PRE-I-SPY Phase I/Ib Oncology Platform Program

PRE-Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging And moLecular Analysis: A Phase I/Ib Platform Trial

Evaluate the number of adverse events related to the treatment according to the current version of CTCAE during the trial.

To determine the safety and tolerability of new agents/regimens in participants with certain advanced solid tumors and breast cancer. DLT rate (number of participants who experience a protocol defined DLT/total number of DLT cohort participants at that dose).

The maximum dose level (mg/kg) which is not eliminated.

Using all available data, computation of RP2D (mg/kg), which may not be the MTD.

To obtain preliminary efficacy data of the new agents/regimens in participants with certain advanced solid tumors and breast cancer.

To provide descriptive assessment of Progression Free Survival (PFS) of the new agents/regimens with certain advanced solid tumors and breast cancer

To obtain preliminary Clinical Benefit Rate (CBR) at 6 months of participants treated with the new agents/regimens.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
ETHAN - ET for Male BC	NCT05501704	Male Breast Can... Hormone Recepto... Hormone Recepto...	Tamoxifen Anastrozole Degarelix Abemaciclib	18 Years -	Dana-Farber Cancer Institute
ETHAN - ET for Male BC	NCT05501704	Male Breast Can... Hormone Recepto... Hormone Recepto...	Tamoxifen Anastrozole Degarelix Abemaciclib	18 Years -	Dana-Farber Cancer Institute
ETHAN - ET for Male BC	NCT05501704	Male Breast Can... Hormone Recepto... Hormone Recepto...	Tamoxifen Anastrozole Degarelix Abemaciclib	18 Years -	Dana-Farber Cancer Institute
PRE-I-SPY Phase I/Ib Oncology Platform Program	NCT05868226	HER2-positive B... Metastatic Canc... Metastatic Brea... Metastatic HER2-positive M... HER2 Mutation-R... HER-2 Protein O... HER2-negative B... Triple Negative... HR Positive Hormone Recepto... Estrogen Recept... Progesterone Re... Hormone Recepto... Solid Tumor Solid Tumor, Ad... Solid Carcinoma HER2 Low Breast... HER2 Low Breast... ER Positive Bre... PR-positive Bre...	ALX148 Fam-Trastuzumab... Zanidatamab Tucatinib	18 Years -	QuantumLeap Healthcare Collaborative

Spots Global Cancer Trial Database for hormone receptor negative breast carcinoma