Undersøgelse for at teste lægemidlet darolutamid sammen med lægemidlerne leuprolidacetat og exemestan hos patienter med tilbagevendende ovariegranulosacelletumorer
Et fase II-studie af androgenreceptor (AR) hæmning af darolutamid i kombination med leuprolidacetat og exemestan i recidiverende voksen-type ovariegranulosacelletumor
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.
Studieoversigt
Status
Status
Betingelser
Betingelser
Intervention / Behandling
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Undersøgelsestype
Tilmelding (Faktiske)
Tilmelding
Fase
Fase
- Fase 2
Kontakter og lokationer
Studiesteder
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California
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Los Angeles, California, Forenede Stater, 90048
- Cedars-Sinai Medical Center
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Delaware
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Newark, Delaware, Forenede Stater, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Forenede Stater, 19713
- Medical Oncology Hematology Consultants PA
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Idaho
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Boise, Idaho, Forenede Stater, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Caldwell, Idaho, Forenede Stater, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, Forenede Stater, 83814
- Kootenai Health - Coeur d'Alene
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Nampa, Idaho, Forenede Stater, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Post Falls, Idaho, Forenede Stater, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, Forenede Stater, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Illinois
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Chicago, Illinois, Forenede Stater, 60611
- Northwestern University
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Danville, Illinois, Forenede Stater, 61832
- Carle at The Riverfront
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DeKalb, Illinois, Forenede Stater, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Effingham, Illinois, Forenede Stater, 62401
- Carle Physician Group-Effingham
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Geneva, Illinois, Forenede Stater, 60134
- Northwestern Medicine Cancer Center Delnor
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Grayslake, Illinois, Forenede Stater, 60030
- Northwestern Medicine Grayslake Outpatient Center
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Lake Forest, Illinois, Forenede Stater, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, Forenede Stater, 61938
- Carle Physician Group-Mattoon/Charleston
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Orland Park, Illinois, Forenede Stater, 60462
- Northwestern Medicine Orland Park
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Urbana, Illinois, Forenede Stater, 61801
- Carle Cancer Center
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Warrenville, Illinois, Forenede Stater, 60555
- Northwestern Medicine Cancer Center Warrenville
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Indiana
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Indianapolis, Indiana, Forenede Stater, 46260
- Ascension Saint Vincent Indianapolis Hospital
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Iowa
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Iowa City, Iowa, Forenede Stater, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Maine
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Scarborough, Maine, Forenede Stater, 04074
- MaineHealth Maine Medical Center- Scarborough
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Michigan
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Ann Arbor, Michigan, Forenede Stater, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Forenede Stater, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Battle Creek, Michigan, Forenede Stater, 49017
- Bronson Battle Creek
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Brighton, Michigan, Forenede Stater, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Canton, Michigan, Forenede Stater, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
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Chelsea, Michigan, Forenede Stater, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Flint, Michigan, Forenede Stater, 48503
- Hurley Medical Center
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Flint, Michigan, Forenede Stater, 48503
- Genesee Hematology Oncology PC
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Flint, Michigan, Forenede Stater, 48503
- Genesys Hurley Cancer Institute
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Flint, Michigan, Forenede Stater, 48503
- Cancer Hematology Centers - Flint
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Grand Rapids, Michigan, Forenede Stater, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, Forenede Stater, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, Forenede Stater, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Forenede Stater, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Forenede Stater, 49009
- Beacon Kalamazoo Cancer Center
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Livonia, Michigan, Forenede Stater, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
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Muskegon, Michigan, Forenede Stater, 49444
- Trinity Health Muskegon Hospital
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Norton Shores, Michigan, Forenede Stater, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Reed City, Michigan, Forenede Stater, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, Forenede Stater, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Traverse City, Michigan, Forenede Stater, 49684
- Munson Medical Center
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Wyoming, Michigan, Forenede Stater, 49519
- University of Michigan Health - West
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Ypsilanti, Michigan, Forenede Stater, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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Missouri
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St Louis, Missouri, Forenede Stater, 63141
- Mercy Hospital Saint Louis
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Montana
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Anaconda, Montana, Forenede Stater, 59711
- Community Hospital of Anaconda
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Billings, Montana, Forenede Stater, 59101
- Billings Clinic Cancer Center
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Bozeman, Montana, Forenede Stater, 59715
- Bozeman Health Deaconess Hospital
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Great Falls, Montana, Forenede Stater, 59405
- Benefis Sletten Cancer Institute
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Missoula, Montana, Forenede Stater, 59804
- Community Medical Center
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Nebraska
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Omaha, Nebraska, Forenede Stater, 68198
- University of Nebraska Medical Center
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North Carolina
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Charlotte, North Carolina, Forenede Stater, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Concord, North Carolina, Forenede Stater, 28025
- Atrium Health Cabarrus/LCI-Concord
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Ohio
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Centerville, Ohio, Forenede Stater, 45459
- Miami Valley Hospital South
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Cleveland, Ohio, Forenede Stater, 44195
- Cleveland Clinic Foundation
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Sylvania, Ohio, Forenede Stater, 43560
- ProMedica Flower Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Forenede Stater, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Ontario, Oregon, Forenede Stater, 97914
- Saint Alphonsus Cancer Care Center-Ontario
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Portland, Oregon, Forenede Stater, 97210
- Legacy Good Samaritan Hospital and Medical Center
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Tualatin, Oregon, Forenede Stater, 97062
- Legacy Meridian Park Hospital
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Washington
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Vancouver, Washington, Forenede Stater, 98686
- Legacy Salmon Creek Hospital
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West Virginia
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Charleston, West Virginia, Forenede Stater, 25304
- West Virginia University Charleston Division
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Wisconsin
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Appleton, Wisconsin, Forenede Stater, 54911
- ThedaCare Regional Cancer Center
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Milwaukee, Wisconsin, Forenede Stater, 53226
- Medical College of Wisconsin
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Deltagelseskriterier
Berettigelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
Inclusion Criteria:
-
Physicians should consider the following when evaluating if the patient is appropriate for this protocol:
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Patients must have adequate health that permits completion of the study requirements and required follow up
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For patients with known human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV) infection:
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
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Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
-
In addition:
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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
- Submission of tissue is required. Investigators should check with their pathology department regarding release of tissue before approaching patients about participation in the trial
- Histologically confirmed diagnosis of recurrent adult-type granulosa cell tumor
- Patient must have measurable disease. Measurable disease is defined in the protocol per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded). Each lesion must be ≥ 10 mm when measured by CT or MRI. Lymph nodes must be ≥ 15 mm in short axis when measured by CT or MRI
- Patient must have had ≥1 treatment regimen
- Subject must have progressed on an aromatase inhibitor (letrozole, exemestane, anastrozole) in a prior treatment line
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
- Not pregnant and not nursing
- Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3
- Platelets ≥ 100,000 cells/mm^3
- Hemoglobin ≥ 8 g/dl
- Creatinine clearance (CrCL) of ≥ 30 mL/min by the Cockcroft-Gault formula
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (patients with known Gilbert's disease who have bilirubin level ≤ 3 x ULN may be enrolled)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 x institutional ULN
- Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
- No active infection requiring parenteral antibiotics
- Patients with current evidence of intra-abdominal abscess, abdominal/pelvic fistula (not diverted), gastrointestinal perforation, gastrointestinal (GI) obstruction, and/or need for drainage nasogastric or gastrostomy tube
- The patient or a legally authorized representative must provide study-specific informed consent prior to study entry and, for patients treated in the United States (U.S.), authorization permitting release of personal health information
Exclusion Criteria:
- Prior treatment with AR inhibitors
- Known hypersensitivity to the study drugs or their ingredients
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: N/A
- Interventionel model: Enkelt gruppeopgave
- Maskning: Ingen (Åben etiket)
Antal våben
Våben og indgreb
Deltagergruppe / ArmDeltagergruppe / Arm |
Intervention / BehandlingIntervention / Behandling |
|---|---|
|
Eksperimentel: Treatment (exemestane, darolutamide, leuprolide acetate)
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. |
Given PO
Andre navne:
Undergo MRI
Andre navne:
Undergo PET/CT
Andre navne:
Undergo chest x-ray
Andre navne:
Undergo CT and/or PET/CT
Andre navne:
Given PO
Andre navne:
Undergo archived tissue and blood sample collection
Andre navne:
Given IM
Andre navne:
|
Hvad måler undersøgelsen?
Primære resultatmål
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Objective Response Rate (ORR)
Tidsramme: Within 9 months of initiating study treatment
|
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. |
Within 9 months of initiating study treatment
|
Sekundære resultatmål
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Duration of Response
Tidsramme: Within 9 months of initiating study treatment
|
The duration of overall response is measured from the time measurement criteria are first met for CR or PR (whichever is first recorded) until the first date that recurrence or progressive disease is objectively documented. Only one patient experienced a partial response (PR) within the 9-month response window. Therefore the 95% confidence interval for the duration of response was not estimated. |
Within 9 months of initiating study treatment
|
|
Progression-free Survival (PFS)
Tidsramme: up to 22 months
|
Progression-free survival (PFS) is defined as the duration of time 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. Patients with no follow-up will be censored 1 day after enrollment. Will be graphed using Kaplan-Meier methods. Median PFS will be estimated with corresponding 95% confidence intervals. |
up to 22 months
|
|
Overall Survival (OS)
Tidsramme: up to 22 months
|
Overall survival is defined as the duration of time from study entry to time of death or the date of last contact. Patients with no follow-up will be censored 1 day after enrollment. Will be graphed using Kaplan-Meier methods. Median OS will be estimated with corresponding 95% confidence intervals. The OS was not reached due to the study early termination for futility. Thus the death rate was reported instead of survival time. |
up to 22 months
|
|
Incidence of Adverse Events
Tidsramme: Adverse Events were assessed up to 9 months, All Cause Mortality was assessed up to 22 months.
|
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. |
Adverse Events were assessed up to 9 months, All Cause Mortality was assessed up to 22 months.
|
Samarbejdspartnere og efterforskere
Sponsor
Sponsor
Samarbejdspartnere
Samarbejdspartnere
Efterforskere
Efterforskere
- Ledende efterforsker: Elizabeth Hopp, NRG Oncology
Publikationer og nyttige links
Generelle publikationer
- Erfani H, Martynova A, Matsuzaki S, Matsuo K, Roman LD, Sood AK, Kurnit KC, Westin SN. Androgen receptor as a therapeutic target in endometrial cancer: a narrative review. Int J Gynecol Cancer. 2026 Jun;36(6):104698. doi: 10.1016/j.ijgc.2026.104698. Epub 2026 Apr 11.
- Hopp EE, Enserro D, Campos S, Chitiyo V, Huang G, Lankes H, Crane EK, Hoekstra A, Siedel J, Richardson DL, Aghajanian C, Rader JS, Covens A. A phase II study of androgen receptor inhibition by darolutamide in combination with leuprolide acetate and exemestane in recurrent adult-type ovarian granulosa cell tumor. Gynecol Oncol. 2026 Aug 10;212:98-105. doi: 10.1016/j.ygyno.2026.07.017. Online ahead of print.
Datoer for undersøgelser
Studer store datoer
Studiestart (Faktiske)
Studiestart
Primær færdiggørelse (Faktiske)
Primær færdiggørelse
Studieafslutning (Faktiske)
Studieafslutning
Datoer for studieregistrering
Først indsendt
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først indsendt, der opfyldte QC-kriterier
Først opslået (Faktiske)
Først opslået
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering sendt
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Granulosa -celletumor i æggestokken
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Hypofysehormon-frigivende hormoner
- Hypothalamiske hormoner
- Peptidhormoner
- Neuropeptider
- Peptider
- Aminosyrer, peptider og proteiner
- Oligopeptider
- Nervevævsproteiner
- Proteiner
- Undersøgelsesteknikker
- Kliniske laboratorieteknikker
- Diagnostiske teknikker og procedurer
- Diagnose
- Fysiske fænomener
- Kemiteknikker, analytisk
- Spektrumanalyse
- Elektromagnetiske fænomener
- Magnetiske fænomener
- Elektromagnetisk stråling
- Stråling
- Stråling, ioniserende
- Gonadotropin-frigivende hormon
- Leuprolid
- Luprolide acetatgeldepot
- Darolutamid
- Håndtering af eksemplar
- Magnetisk resonansspektroskopi
- Røntgenstråler
- Exemestane
Andre undersøgelses-id-numre
Andre undersøgelses-id-numre
- NCI-2023-06524
- U10CA180868 (U.S. NIH-bevilling/kontrakt)
- NCI-2023-06524 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- NRG-GY033 (Anden identifikator: CTEP)
- NRG-GY033 (Anden identifikator: NRG Oncology)
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
IPD-planbeskrivelse
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.
Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter
Studerer et amerikansk FDA-reguleret lægemiddelprodukt
Studerer et amerikansk FDA-reguleret enhedsprodukt
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