Title
A Phase 2 Study of Darolutamide in Combination with Leuprolide Acetate in Hormone-Therapy Naïve Recurrent and/or Metastatic Androgen Receptor (AR) Positive Salivary Gland Cancer

Description
This phase II trial tests how well darolutamide and leuprolide acetate work in treating patients with androgen receptor positive salivary cancer that has spread from where it first started (primary site) to other places in the body (metastatic), cannot be removed by surgery (unresectable) or that has come back after a period of responding to prior therapy (recurrent). Darolutamide is in a class of medications called androgen receptor inhibitors. It works by blocking the effects of androgen (a male reproductive hormone) to stop the growth and spread of cancer cells. Leuprolide acetate is in a class of medications called gonadotropin-releasing hormone (GnRH) agonists. It works by decreasing the amount of certain hormones in the body. Giving darolutamide in combination with leuprolide acetate may help to stop the growth of tumor cells that need androgens to grow or shrink them.

Objective
PRIMARY OBJECTIVE:

I. To evaluate the best overall response rate (BOR) of recurrent/metastatic androgen receptor positive (AR+) salivary gland cancer (SGC) patients within one year of darolutamide and androgen deprivation therapy (ADT).

SECONDARY OBJECTIVES:

I. To evaluate progression-free survival (PFS). II. To evaluate overall survival (OS). III. To evaluate toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

EXPLORATORY OBJECTIVES:

I. To evaluate molecular, genomic and transcriptomic biomarkers in serial research biopsies obtained before and on darolutamide and ADT.

II. To evaluate the differences in BOR, PFS, OS with darolutamide and ADT treatment among patients who did and did not receive prior systemic therapy for AR+ SGC.

Treatment Patients receive darolutamide orally (PO) twice daily (BID) on days 1-28 of each cycle and leuprolide acetate intramuscularly (IM) every 4 or 12 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, collection of blood samples, and computed tomography (CT)/magnetic resonance imaging (MRI) throughout the trial.

After completion of study treatment, patients are followed every 3-6 months for 2 years after treatment discontinuation or until death, whichever occurs first.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Head and Neck

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital