This phase II trial tests how well darolutamide in combination with leuprolide acetate and exemestane works in treating patients with ovarian granulosa cell tumors that have come back after a period of improvement (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 tumor cells. Leuprolide acetate is in a class of medications called gonadotropin-releasing hormone agonists. It works by decreasing the amount of certain hormones in the body. Exemestane is in a class of medications called aromatase inhibitors which has anti-estrogen and anticancer activities. Exemestane binds to and inhibits the enzyme aromatase, thereby blocking the conversion of androgens to estrogens. This lowers estrogen levels in the blood circulation causing the tumor cells to grow more slowly or stop growing completely. The combination of darolutamide, leuprolide acetate, and exemestane may be an effective approach to shrinking or stabilizing recurrent ovarian granulosa cell tumors or preventing them from coming back.
PRIMARY OBJECTIVE: I. To determine the objective response rate of darolutamide, leuprolide acetate, and exemestane in recurrent adult-type granulosa cell tumors of the ovary (AGCT). SECONDARY OBJECTIVES: I. To determine duration of response of darolutamide, leuprolide acetate, and exemestane in recurrent adult-type granulosa cell tumors of the ovary (AGCT). II. To determine progression-free survival of darolutamide, leuprolide acetate, and exemestane when used in recurrent adult-type granulosa cell tumors of ovary (AGCT). III. To determine overall survival of darolutamide, leuprolide acetate, and exemestane when used in recurrent adult-type granulosa cell tumors of ovary (AGCT). IV. To elucidate the toxicities of darolutamide, leuprolide acetate, and exemestane when used in recurrent adult-type granulosa cell tumors of ovary (AGCT). EXPLORATORY OBJECTIVE: I. To determine biomarkers predictive of response to darolutamide, leuprolide acetate, and exemestane. OUTLINE: Patients receive exemestane orally (PO) once daily (QD) and darolutamide PO twice daily (BID) starting on days -14 to -7 prior to cycle 1, day 1 (C1D1) and then on days 1-28 of each cycle. Patients receive leuprolide acetate intramuscularly (IM) on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo chest computed tomography (CT) or chest x-ray and CT, magnetic resonance imaging (MRI), or positron emission tomography (PET)/CT as well as blood sample collection throughout the study. Patients undergo collection of archived tissue during screening. Upon completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Undergo archived tissue and blood sample collection
Undergo chest x-ray
Undergo CT and/or PET/CT
Given PO
Given PO
Given IM
Undergo MRI
Undergo PET/CT
Cedars Sinai Medical Center
Los Angeles, California, United States
Helen F Graham Cancer Center
Newark, Delaware, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware, United States
Saint Alphonsus Cancer Care Center-Boise
Boise, Idaho, United States
Saint Alphonsus Cancer Care Center-Caldwell
Caldwell, Idaho, United States
Objective response rate
Defined as a complete response (CR) or partial response (PR) as assessed by Response Evaluation Criteria in Solid Tumors version 1.1 criteria. Exact 95% confidence limits, accounting for interim analysis, will be provided in the final report.
Time frame: Within 9 months of initiating study treatment
Duration of response
Median duration of response with a corresponding 95% confidence interval will be estimated. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. Stable disease is measured from the start of the treatment until the criteria for progression are met, taking as reference the smallest measurements recorded since date of study entry, including the baseline measurements.
Time frame: From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Progression-free survival (PFS)
Will be graphed using Kaplan-Meier methods. Median PFS will be estimated with corresponding 95% confidence intervals.
Time frame: From study entry to time of progression or death, whichever occurs first, or date of last contact with known progression free status if neither progression nor death has occurred, assessed up to 5 years
Overall survival (OS)
Will be graphed using Kaplan-Meier methods. Median OS will be estimated with corresponding 95% confidence intervals.
Time frame: From study entry to time of death or the date of last contact, assessed up to 5 years
Incidence of adverse events
Common Terminology Criteria for Adverse Events version 5 will be used to grade and categorize adverse events. Safety will be assessed beginning with the initial dose of any treatment. Descriptive statistics, including frequencies of maximum grade of adverse events by term and category will be reported. Adverse events categorized as grade 5 will be individually reported.
Time frame: Up to 5 years
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Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho, United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho, United States
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Post Falls, Idaho, United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho, United States
Northwestern University
Chicago, Illinois, United States
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