PRIMARY OBJECTIVE:~I. To evaluate the best overall response rate (BOR) of recurrent/metastatic androgen receptor positive (AR+) salivary gland cancer (SGC) patients with 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.~OUTLINE: Patients receive darolutamide orally (PO) and leuprolide acetate intramuscularly (IM) on study. Patients undergo tumor biopsies at baseline and after initiation of study treatments and their blood is collected, throughout the study.~Patients will be followed every 3-6 months for 2 years after treatment discontinuation or until death, whichever occurs first.
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, 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.