A Phase 2 interventional study of Biospecimen Collection and Chest Radiography in Adult Ovarian Granulosa Cell Tumor, sponsored by National Cancer Institute (NCI). Active, not recruiting at 66 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-28.
Sponsored by National Cancer Institute (NCI) · Phase 2, Interventional, and Treatment
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.
Physicians should consider the following when evaluating if the patient is appropriate for this protocol:
For patients with known human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infection:
In addition:
The effects of the combination of darolutamide, leuprolide acetate, and exemestane on the developing human fetus are unknown. For this reason, and because androgen receptor inhibitor agents as well as other therapeutic agents used in this trial are known to be teratogenic, participants of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during study therapy and for 1 month following the completion of study therapy. Should a participant become pregnant or suspect pregnancy while participating in this study, they should inform their treating physician immediately
Exclusion Criteria:
Patients receive exemestane PO QD and darolutamide PO BID starting on days -14 to -7 prior to C1D1 and then on days 1-28 of each cycle. Patients receive leuprolide acetate 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 CT or chest x-ray and CT, MRI, or PET/CT as well as blood sample collection throughout the study. Patients undergo collection of archived tissue during screening.
Procedure: Biospecimen Collection · Procedure: Chest Radiography · Procedure: Computed Tomography · Drug: Darolutamide · Drug: Exemestane · Drug: Leuprolide Acetate · Procedure: Magnetic Resonance Imaging · Procedure: Positron Emission Tomography
Undergo archived tissue and blood sample collection
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
Undergo chest x-ray
Also known as: Chest X-ray
Undergo CT and/or PET/CT
Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography
Given PO
Also known as: Antiandrogen ODM-201, BAY 1841788, BAY-1841788, BAY1841788, Nubeqa, ODM 201, ODM-201, ODM201
Given PO
Also known as: Aromasin, FCE-24304
Given IM
Also known as: A 43818, A-43818, A43818, Abbott 43818, Abbott-43818, Carcinil, Depo-Eligard, Eligard, Enanton, Enantone, Enantone-Gyn, Fensolvi, Ginecrin, LEUP, Leuplin, Leuprorelin Acetate, Lucrin, Lucrin Depot, Luprodex Depot, Lupron, Lupron Depot, Lupron Depot-3 Month, Lupron Depot-4 Month, Lupron Depot-Ped, Lutrate, Procren, Procrin, Prostap, TAP 144, TAP-144, TAP144, Trenantone, Uno-Enantone, Viadur
Undergo MRI
Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI
Undergo PET/CT
Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT
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
Biomarkers predictive of response
Hormone receptor positivity (including estrogen receptor, progesterone receptor, and androgen receptor) will be assessed via immunohistochemistry (IHC). The percent positivity and median intensity will be assessed for each hormone receptor per subject. IHC results will be correlated with subject response on the study drug regimen. Logistic regression will be used to estimate an odds ratio with 95% confidence limits. IHC results will also be correlated with PFS and OS, using Cox-proportional hazards modeling to estimate hazard ratios with 95% confidence limits. No hypothesis testing is planned.
Time frame: Up to 5 years
Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
This study is active, not recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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Granulosa cell tumor of the ovary
National Cancer Institute (NCI)