Estudio para probar el fármaco darolutamida junto con los fármacos acetato de leuprolida y exemestano en pacientes con tumores recurrentes de células de la granulosa de ovario
Un estudio de fase II de la inhibición del receptor de andrógenos (AR) por darolutamida en combinación con acetato de leuprolida y exemestano en el tumor recidivante de células de la granulosa ovárica de tipo adulto
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.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Tipo de estudio
Inscripción (Actual)
Inscripción
Fase
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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California
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Los Angeles, California, Estados Unidos, 90048
- Cedars-Sinai Medical Center
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Delaware
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Newark, Delaware, Estados Unidos, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Estados Unidos, 19713
- Medical Oncology Hematology Consultants PA
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Idaho
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Boise, Idaho, Estados Unidos, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Caldwell, Idaho, Estados Unidos, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, Estados Unidos, 83814
- Kootenai Health - Coeur d'Alene
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Nampa, Idaho, Estados Unidos, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Post Falls, Idaho, Estados Unidos, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, Estados Unidos, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Illinois
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Chicago, Illinois, Estados Unidos, 60611
- Northwestern University
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Danville, Illinois, Estados Unidos, 61832
- Carle at The Riverfront
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DeKalb, Illinois, Estados Unidos, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Effingham, Illinois, Estados Unidos, 62401
- Carle Physician Group-Effingham
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Geneva, Illinois, Estados Unidos, 60134
- Northwestern Medicine Cancer Center Delnor
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Grayslake, Illinois, Estados Unidos, 60030
- Northwestern Medicine Grayslake Outpatient Center
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Lake Forest, Illinois, Estados Unidos, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, Estados Unidos, 61938
- Carle Physician Group-Mattoon/Charleston
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Orland Park, Illinois, Estados Unidos, 60462
- Northwestern Medicine Orland Park
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Urbana, Illinois, Estados Unidos, 61801
- Carle Cancer Center
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Warrenville, Illinois, Estados Unidos, 60555
- Northwestern Medicine Cancer Center Warrenville
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Indiana
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Indianapolis, Indiana, Estados Unidos, 46260
- Ascension Saint Vincent Indianapolis Hospital
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Iowa
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Iowa City, Iowa, Estados Unidos, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Maine
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Scarborough, Maine, Estados Unidos, 04074
- MaineHealth Maine Medical Center- Scarborough
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Michigan
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Ann Arbor, Michigan, Estados Unidos, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Estados Unidos, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Battle Creek, Michigan, Estados Unidos, 49017
- Bronson Battle Creek
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Brighton, Michigan, Estados Unidos, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Canton, Michigan, Estados Unidos, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
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Chelsea, Michigan, Estados Unidos, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Flint, Michigan, Estados Unidos, 48503
- Hurley Medical Center
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Flint, Michigan, Estados Unidos, 48503
- Genesee Hematology Oncology PC
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Flint, Michigan, Estados Unidos, 48503
- Genesys Hurley Cancer Institute
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Flint, Michigan, Estados Unidos, 48503
- Cancer Hematology Centers - Flint
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Grand Rapids, Michigan, Estados Unidos, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, Estados Unidos, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, Estados Unidos, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Estados Unidos, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Estados Unidos, 49009
- Beacon Kalamazoo Cancer Center
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Livonia, Michigan, Estados Unidos, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
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Muskegon, Michigan, Estados Unidos, 49444
- Trinity Health Muskegon Hospital
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Norton Shores, Michigan, Estados Unidos, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Reed City, Michigan, Estados Unidos, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, Estados Unidos, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Traverse City, Michigan, Estados Unidos, 49684
- Munson Medical Center
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Wyoming, Michigan, Estados Unidos, 49519
- University of Michigan Health - West
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Ypsilanti, Michigan, Estados Unidos, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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Missouri
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St Louis, Missouri, Estados Unidos, 63141
- Mercy Hospital Saint Louis
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Montana
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Anaconda, Montana, Estados Unidos, 59711
- Community Hospital of Anaconda
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Billings, Montana, Estados Unidos, 59101
- Billings Clinic Cancer Center
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Bozeman, Montana, Estados Unidos, 59715
- Bozeman Health Deaconess Hospital
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Great Falls, Montana, Estados Unidos, 59405
- Benefis Sletten Cancer Institute
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Missoula, Montana, Estados Unidos, 59804
- Community Medical Center
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Nebraska
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Omaha, Nebraska, Estados Unidos, 68198
- University of Nebraska Medical Center
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North Carolina
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Charlotte, North Carolina, Estados Unidos, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Concord, North Carolina, Estados Unidos, 28025
- Atrium Health Cabarrus/LCI-Concord
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Ohio
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Centerville, Ohio, Estados Unidos, 45459
- Miami Valley Hospital South
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Cleveland, Ohio, Estados Unidos, 44195
- Cleveland Clinic Foundation
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Sylvania, Ohio, Estados Unidos, 43560
- ProMedica Flower Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Estados Unidos, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Ontario, Oregon, Estados Unidos, 97914
- Saint Alphonsus Cancer Care Center-Ontario
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Portland, Oregon, Estados Unidos, 97210
- Legacy Good Samaritan Hospital and Medical Center
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Tualatin, Oregon, Estados Unidos, 97062
- Legacy Meridian Park Hospital
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Washington
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Vancouver, Washington, Estados Unidos, 98686
- Legacy Salmon Creek Hospital
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West Virginia
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Charleston, West Virginia, Estados Unidos, 25304
- West Virginia University Charleston Division
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Wisconsin
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Appleton, Wisconsin, Estados Unidos, 54911
- ThedaCare Regional Cancer Center
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Milwaukee, Wisconsin, Estados Unidos, 53226
- Medical College of Wisconsin
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Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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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
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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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
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Experimental: 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
Otros nombres:
Undergo MRI
Otros nombres:
Undergo PET/CT
Otros nombres:
Undergo chest x-ray
Otros nombres:
Undergo CT and/or PET/CT
Otros nombres:
Given PO
Otros nombres:
Undergo archived tissue and blood sample collection
Otros nombres:
Given IM
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Objective Response Rate (ORR)
Periodo de tiempo: Within 9 months of initiating study treatment
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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
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Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Duration of Response
Periodo de tiempo: Within 9 months of initiating study treatment
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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
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Progression-free Survival (PFS)
Periodo de tiempo: up to 22 months
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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
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Overall Survival (OS)
Periodo de tiempo: up to 22 months
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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
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Incidence of Adverse Events
Periodo de tiempo: Adverse Events were assessed up to 9 months, All Cause Mortality was assessed up to 22 months.
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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.
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Colaboradores e Investigadores
Patrocinador
Patrocinador
Colaboradores
Colaboradores
Investigadores
Investigadores
- Investigador principal: Elizabeth Hopp, NRG Oncology
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Inicio del estudio
Finalización primaria (Actual)
Finalización primaria
Finalización del estudio (Actual)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Tumor de células de granulosa del ovario
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Hormonas de liberación de hormonas pituitarias
- Hormonas hipotalámicas
- Hormonas peptídicas
- Neuropéptidos
- Péptidos
- Aminoácidos, péptidos y proteínas
- Oligopéptidos
- Proteínas del tejido nervioso
- Proteínas
- Técnicas de investigación
- Técnicas de laboratorio clínico
- Técnicas y procedimientos de diagnóstico
- Diagnóstico
- Fenómeno físico
- Técnicas de química, analítica
- Análisis de espectro
- Fenómenos electromagnéticos
- Fenómeno magnético
- Radiación electromagnética
- Radiación
- Radiación, ionizante
- Hormona liberadora de gonadotropina
- Leuprolida
- depósito de gel de acetato de luprolide
- darolutamida
- Manejo de muestras
- Espectroscopía de resonancia magnética
- Rayos X
- exemestano
Otros números de identificación del estudio
Otros números de identificación del estudio
- NCI-2023-06524
- U10CA180868 (Subvención/contrato del NIH de EE. UU.)
- NCI-2023-06524 (Identificador de registro: CTRP (Clinical Trial Reporting Program))
- NRG-GY033 (Otro identificador: CTEP)
- NRG-GY033 (Otro identificador: NRG Oncology)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
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.
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .