Comparing Different Endocrine Therapies for Male Breast Cancer, ETHAN Trial

PRIMARY OBJECTIVES:

I. To evaluate the comparative efficacy of tamoxifen, anastrozole, and anastrozole in combination with degarelix for the treatment of men with stage I to III hormone receptor (HR)+ HER2- breast cancer, as measured by reduction of Ki-67 from the diagnostic biopsy to the research biopsy at the end of the three-week window period.

II. To evaluate the comparative efficacy of tamoxifen with or without abemaciclib, and anastrozole plus degarelix with or without abemaciclib for the neoadjuvant treatment of men with stage I to III HR+ HER2- breast cancer, as measured by residual cancer burden (RCB) index at surgery.

SECONDARY OBJECTIVES:

I. To evaluate the physiologic endocrine changes that occur as a result of treatment with tamoxifen, anastrozole and anastrozole with degarelix as measured by estradiol and testosterone levels at baseline, at the end of the three-week window period and during the neoadjuvant phase.

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

III. To determine the safety and tolerability of the study treatments.

IV. To assess for feasibility and futility of the trial design and treatments used.

V. To evaluate the impact of the treatments on patient-reported outcomes (PROs) and quality of life (QoL) measures using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLC-C30) and Breast Cancer-Specific Questionnaire (BR23), adapted by replacing female-specific items with male-specific sexual activity/function items from PR25.

EXPLORATORY OBJECTIVES:

I. To compare tumor genomic profiles before and after treatment with abemaciclib, with a focus on genes related to CDK4/6 inhibition (RB1, CCNE1, CCNE2, CCND1, AKT1, RAS, AURKA).

II. To evaluate germline BRCA status as a predictor of response to the specific endocrine regimens.

III. To evaluate event-free survival (EFS).

IV. To evaluate endocrine therapy response at the molecular level and in in-vivo models.

V. To quantify the degree of apoptosis induced by endocrine therapy with or without abemaciclib.

OUTLINE:

WINDOW PHASE: Patients are randomized to 1 of 3 arms.

ARM A: Patients receive tamoxifen orally (PO) once daily (QD) on days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo a biopsy. Patients also undergo mammography with ultrasound or magnetic resonance imaging (MRI) during screening.

ARM B: Patients receive anastrozole PO QD on days 1-21 in the absence of disease progression or unacceptable toxicity. Patients then undergo a biopsy. Patients also undergo mammography with ultrasound or MRI during screening.

ARM C: Patients receive anastrozole PO QD on days 1-21 and degarelix subcutaneously (SC) on day 1 in the absence of disease progression or unacceptable toxicity. Patients then undergo a biopsy. Patients also undergo mammography with ultrasound or MRI during screening.

NEOADJUVANT PHASE: Patients in Arm A are randomized to Arm D or Arm E. Patients in Arm B and Arm C are randomized to Arm F or Arm G.

ARM D: Patients receive tamoxifen PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. Patients also undergo collection of blood samples and undergo mammography with ultrasound or MRI on the trial.

ARM E: Patients receive tamoxifen PO QD and abemaciclib PO twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. Patients also undergo collection of blood samples and undergo mammography with ultrasound or MRI on the trial.

ARM F: Patients receive anastrozole PO QD on days 1-28 and degarelix SC on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. Patients also undergo collection of blood samples and undergo mammography with ultrasound or MRI on the trial.

ARM G: Patients receive anastrozole PO QD and abemaciclib PO BID on days 1-28 and degarelix SC on day 1 of each cycle. Cycles repeat every 28 days for 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. Patients also undergo collection of blood samples and undergo mammography with ultrasound or MRI on the trial.

After completion of study treatment, patients are followed up every year for up to 10 years.