- ICH GCP
- USA klinikai vizsgálatok nyilvántartása
- Klinikai vizsgálat NCT06169124
Tanulmány a darolutamid gyógyszer, a leuprolid-acetát és az exemesztán gyógyszerekkel együtt történő tesztelésére visszatérő petefészek-granulosa sejttumorban szenvedő betegeknél
Az androgénreceptor (AR) darolutamiddal való leuprolid-acetáttal és exemesztánnal kombinált gátlásának II. fázisú vizsgálata visszatérő felnőtt típusú petefészek granulóza sejttumorban
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.
A tanulmány áttekintése
Állapot
Körülmények
Részletes leírás
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.
Tanulmány típusa
Beiratkozás (Tényleges)
Fázis
- 2. fázis
Kapcsolatok és helyek
Tanulmányi helyek
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California
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Los Angeles, California, Egyesült Államok, 90048
- Cedars-Sinai Medical Center
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Delaware
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Newark, Delaware, Egyesült Államok, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Egyesült Államok, 19713
- Medical Oncology Hematology Consultants PA
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Idaho
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Boise, Idaho, Egyesült Államok, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Caldwell, Idaho, Egyesült Államok, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, Egyesült Államok, 83814
- Kootenai Health - Coeur d'Alene
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Nampa, Idaho, Egyesült Államok, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Post Falls, Idaho, Egyesült Államok, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, Egyesült Államok, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Illinois
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Chicago, Illinois, Egyesült Államok, 60611
- Northwestern University
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Danville, Illinois, Egyesült Államok, 61832
- Carle at The Riverfront
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DeKalb, Illinois, Egyesült Államok, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Effingham, Illinois, Egyesült Államok, 62401
- Carle Physician Group-Effingham
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Geneva, Illinois, Egyesült Államok, 60134
- Northwestern Medicine Cancer Center Delnor
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Grayslake, Illinois, Egyesült Államok, 60030
- Northwestern Medicine Grayslake Outpatient Center
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Lake Forest, Illinois, Egyesült Államok, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, Egyesült Államok, 61938
- Carle Physician Group-Mattoon/Charleston
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Orland Park, Illinois, Egyesült Államok, 60462
- Northwestern Medicine Orland Park
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Urbana, Illinois, Egyesült Államok, 61801
- Carle Cancer Center
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Warrenville, Illinois, Egyesült Államok, 60555
- Northwestern Medicine Cancer Center Warrenville
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Indiana
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Indianapolis, Indiana, Egyesült Államok, 46260
- Ascension Saint Vincent Indianapolis Hospital
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Iowa
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Iowa City, Iowa, Egyesült Államok, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Maine
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Scarborough, Maine, Egyesült Államok, 04074
- MaineHealth Maine Medical Center- Scarborough
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Michigan
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Ann Arbor, Michigan, Egyesült Államok, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Egyesült Államok, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Battle Creek, Michigan, Egyesült Államok, 49017
- Bronson Battle Creek
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Brighton, Michigan, Egyesült Államok, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Canton, Michigan, Egyesült Államok, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
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Chelsea, Michigan, Egyesült Államok, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Flint, Michigan, Egyesült Államok, 48503
- Hurley Medical Center
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Flint, Michigan, Egyesült Államok, 48503
- Genesee Hematology Oncology PC
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Flint, Michigan, Egyesült Államok, 48503
- Genesys Hurley Cancer Institute
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Flint, Michigan, Egyesült Államok, 48503
- Cancer Hematology Centers - Flint
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Grand Rapids, Michigan, Egyesült Államok, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, Egyesült Államok, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, Egyesült Államok, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Egyesült Államok, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Egyesült Államok, 49009
- Beacon Kalamazoo Cancer Center
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Livonia, Michigan, Egyesült Államok, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
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Muskegon, Michigan, Egyesült Államok, 49444
- Trinity Health Muskegon Hospital
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Norton Shores, Michigan, Egyesült Államok, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Reed City, Michigan, Egyesült Államok, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, Egyesült Államok, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Traverse City, Michigan, Egyesült Államok, 49684
- Munson Medical Center
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Wyoming, Michigan, Egyesült Államok, 49519
- University of Michigan Health - West
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Ypsilanti, Michigan, Egyesült Államok, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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Missouri
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St Louis, Missouri, Egyesült Államok, 63141
- Mercy Hospital Saint Louis
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Montana
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Anaconda, Montana, Egyesült Államok, 59711
- Community Hospital of Anaconda
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Billings, Montana, Egyesült Államok, 59101
- Billings Clinic Cancer Center
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Bozeman, Montana, Egyesült Államok, 59715
- Bozeman Health Deaconess Hospital
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Great Falls, Montana, Egyesült Államok, 59405
- Benefis Sletten Cancer Institute
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Missoula, Montana, Egyesült Államok, 59804
- Community Medical Center
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Nebraska
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Omaha, Nebraska, Egyesült Államok, 68198
- University of Nebraska Medical Center
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North Carolina
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Charlotte, North Carolina, Egyesült Államok, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Concord, North Carolina, Egyesült Államok, 28025
- Atrium Health Cabarrus/LCI-Concord
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Ohio
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Centerville, Ohio, Egyesült Államok, 45459
- Miami Valley Hospital South
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Cleveland, Ohio, Egyesült Államok, 44195
- Cleveland Clinic Foundation
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Sylvania, Ohio, Egyesült Államok, 43560
- ProMedica Flower Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Egyesült Államok, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Ontario, Oregon, Egyesült Államok, 97914
- Saint Alphonsus Cancer Care Center-Ontario
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Portland, Oregon, Egyesült Államok, 97210
- Legacy Good Samaritan Hospital and Medical Center
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Tualatin, Oregon, Egyesült Államok, 97062
- Legacy Meridian Park Hospital
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Washington
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Vancouver, Washington, Egyesült Államok, 98686
- Legacy Salmon Creek Hospital
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West Virginia
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Charleston, West Virginia, Egyesült Államok, 25304
- West Virginia University Charleston Division
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Wisconsin
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Appleton, Wisconsin, Egyesült Államok, 54911
- ThedaCare Regional Cancer Center
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Milwaukee, Wisconsin, Egyesült Államok, 53226
- Medical College of Wisconsin
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Részvételi kritériumok
Jogosultsági kritériumok
Tanulmányozható életkorok
Egészséges önkénteseket fogad
Tanulmányozható nemek
Leírás
Inclusion Criteria:
-
Physicians should consider the following when evaluating if the patient is appropriate for this protocol:
-
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:
-
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
Tanulási terv
Hogyan készül a tanulmány?
Tervezési részletek
- Elsődleges cél: Kezelés
- Kiosztás: N/A
- Beavatkozó modell: Egyetlen csoportos hozzárendelés
- Maszkolás: Nincs (Open Label)
Fegyverek és beavatkozások
Résztvevő csoport / kar |
Beavatkozás / kezelés |
|---|---|
|
Kísérleti: 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
Más nevek:
Undergo MRI
Más nevek:
Undergo PET/CT
Más nevek:
Undergo chest x-ray
Más nevek:
Undergo CT and/or PET/CT
Más nevek:
Given PO
Más nevek:
Undergo archived tissue and blood sample collection
Más nevek:
Given IM
Más nevek:
|
Mit mér a tanulmány?
Elsődleges eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Objective Response Rate (ORR)
Időkeret: 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
|
Másodlagos eredményintézkedések
Eredménymérő |
Intézkedés leírása |
Időkeret |
|---|---|---|
|
Duration of Response
Időkeret: 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)
Időkeret: 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)
Időkeret: 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
Időkeret: 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.
|
Együttműködők és nyomozók
Szponzor
Együttműködők
Nyomozók
- Kutatásvezető: Elizabeth Hopp, NRG Oncology
Publikációk és hasznos linkek
Általános kiadványok
- 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.
Tanulmányi rekorddátumok
Tanulmány főbb dátumok
Tanulmány kezdete (Tényleges)
Elsődleges befejezés (Tényleges)
A tanulmány befejezése (Tényleges)
Tanulmányi regisztráció dátumai
Először benyújtva
Először nyújtották be, amely megfelel a minőségbiztosítási kritériumoknak
Első közzététel (Tényleges)
Tanulmányi rekordok frissítései
Utolsó frissítés közzétéve (Tényleges)
Az utolsó frissítés elküldve, amely megfelel a minőségbiztosítási kritériumoknak
Utolsó ellenőrzés
Több információ
A tanulmányhoz kapcsolódó kifejezések
További vonatkozó MeSH feltételek
- A petefészek granulosa sejtdaganata
- Hormonok
- Hormonok, hormonpótló anyagok és hormonantagonisták
- Agyalapi mirigy hormon felszabadító hormonok
- Hipotalamusz hormonok
- Peptidhormonok
- Neuropeptidek
- Peptidek
- Aminosavak, peptidek és fehérjék
- Oligopeptidek
- Idegszöveti fehérjék
- Fehérjék
- Nyomozási technikák
- Klinikai laboratóriumi technikák
- Diagnosztikai technikák és eljárások
- Diagnózis
- Fizikai jelenség
- Kémiai technikák, analitikus
- Spektrumelemzés
- Elektromágneses jelenség
- Mágneses jelenség
- Elektromágneses sugárzás
- Sugárzás
- Sugárzás, ionizálás
- Gonadotropin-felszabadító hormon
- Leuprolid
- luprolid -acetát géldepot
- darolutamid
- Minta kezelése
- Mágneses rezonancia spektroszkópia
- Röntgenfelvétel
- exemestán
Egyéb vizsgálati azonosító számok
- NCI-2023-06524
- U10CA180868 (Az Egyesült Államok NIH támogatása/szerződése)
- NCI-2023-06524 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- NRG-GY033 (Egyéb azonosító: CTEP)
- NRG-GY033 (Egyéb azonosító: NRG Oncology)
Terv az egyéni résztvevői adatokhoz (IPD)
Tervezi megosztani az egyéni résztvevői adatokat (IPD)?
IPD terv leírása
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.
Gyógyszer- és eszközinformációk, tanulmányi dokumentumok
Egy amerikai FDA által szabályozott gyógyszerkészítményt tanulmányoz
Egy amerikai FDA által szabályozott eszközterméket tanulmányoz
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