A Phase II, multi-center, single-arm, non-blinded study combining androgen deprivation therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen receptor-positive salivary gland carcinoma, not amenable to surgery or radiation.
This is a Phase II multi-center, single-arm, non-blinded study combining androgen deprivation therapy (ADT) and pembrolizumab for patients with metastatic or locally recurrent androgen receptor-positive salivary gland carcinoma, not amenable to surgery or radiation. Eligible patients will include both those with no prior systemic therapy and those who have failed prior systemic therapy. Patients who have received previous ADT or immunotherapy will be excluded. ADT will consist of goserelin acetate every 4 weeks with the first injection given approximately 2 weeks prior to the first dose of pembrolizumab. Pembrolizumab 200 mg will be given on day 1 of 21-day cycles, starting 2 weeks after initiation of goserelin acetate. Each 21-day period is considered a treatment cycle with therapy continuing for up to 35 cycles, until disease progression, significant toxicity, or patient refusal. Except for fatigue, we do not expect overlapping toxicities with pembrolizumab and ADT, thus the starting doses will be the FDA-approved doses. This study will use a Simon 2-stage phase II trial design. The first stage of the Simon 2-stage design will have a sample size of nine patients. If at least two patients have an objective response by RECIST 1.1 then enrollment will proceed to stage 2 with an additional 11 patients, to a goal of 20 patients. If less than 4 patients out of 20 respond, then the combination treatment will be rejected. Patients will be staged with CT of neck, chest, abdomen, and pelvis at baseline and every 12 weeks while on study. Treatment with both ADT and pembrolizumab will continue until disease progression or intolerable side effects. Archival tumor biopsy tissue must be available at baseline to evaluate for expression of androgen receptor (AR), PD-L1, and tumor-infiltrating lymphocytes (TIL). An optional biopsy will be performed after 4 doses of pembrolizumab to evaluate immune response to combined therapy. Blood will be collected at baseline, cycle 1 day 1, cycle 2 day 1 and cycle 3 day 1 to evaluate for change in lymphocyte subsets by flow cytometry.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Goserelin Acetate, SQ, Q4W
Pembrolizumab, IV, Q3W
Northwestern University Feinberg School of Medicine
Chicago, Illinois, United States
RECRUITINGUniversity of Illinois Cancer Center
Chicago, Illinois, United States
RECRUITINGUniversity of Iowa Hospitals and Clinics
Iowa City, Iowa, United States
Objective Response Rate
Objective response rate to therapy (complete and partial responses) at 3 month intervals after beginning goserelin and pembrolizumab based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
Time frame: 35 months
Progression Free Survival
Determine progression free survival (PFS) at 12 months, according to RECIST 1.1 criteria
Time frame: 12 Months
Disease Control Rate
Disease control rate as defined by stable disease plus objective response (SD+PR+CR), according to RECIST 1.1 criteria
Time frame: 35 Months
Assess Adverse Events
To evaluate the safety and tolerability of pembrolizumab when given with goserelin, grade 3,4,5 adverse events will be summarized according to CTCAE v5 criteria.
Time frame: 35 months
Overall Survival
Determine overall survival (OS) at 12 months, according to RECIST 1.1 criteria
Time frame: 12 Months
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Univeristy of Maryland
Baltimore, Maryland, United States
RECRUITINGUniversity of Michigan Health System
Ann Arbor, Michigan, United States
RECRUITINGUniversity of Minnesota: Masonic Cancer Center
Minneapolis, Minnesota, United States
RECRUITINGUniversity of Wisconsin
Madison, Wisconsin, United States
RECRUITING