Badanie mające na celu przetestowanie leku darolutamid wraz z lekami: octanem leuprolidu i eksemestanem u pacjentek z nawracającymi guzami ziarnistymi jajnika
Badanie II fazy dotyczące hamowania receptora androgenowego (AR) przez darolutamid w skojarzeniu z octanem leuprolidu i eksemestanem w nawracającym guzie ziarniniakowym jajnika typu dorosłego
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.
Przegląd badań
Status
Status
Warunki
Warunki
Interwencja / Leczenie
Interwencja / Leczenie
Szczegółowy opis
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.
Typ studiów
Typ studiów
Zapisy (Rzeczywisty)
Zapisy
Faza
Faza
- Faza 2
Kontakty i lokalizacje
Lokalizacje studiów
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California
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Los Angeles, California, Stany Zjednoczone, 90048
- Cedars-Sinai Medical Center
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Delaware
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Newark, Delaware, Stany Zjednoczone, 19713
- Helen F Graham Cancer Center
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Newark, Delaware, Stany Zjednoczone, 19713
- Medical Oncology Hematology Consultants PA
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Idaho
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Boise, Idaho, Stany Zjednoczone, 83706
- Saint Alphonsus Cancer Care Center-Boise
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Caldwell, Idaho, Stany Zjednoczone, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
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Coeur d'Alene, Idaho, Stany Zjednoczone, 83814
- Kootenai Health - Coeur d'Alene
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Nampa, Idaho, Stany Zjednoczone, 83687
- Saint Alphonsus Cancer Care Center-Nampa
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Post Falls, Idaho, Stany Zjednoczone, 83854
- Kootenai Clinic Cancer Services - Post Falls
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Sandpoint, Idaho, Stany Zjednoczone, 83864
- Kootenai Clinic Cancer Services - Sandpoint
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Illinois
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Chicago, Illinois, Stany Zjednoczone, 60611
- Northwestern University
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Danville, Illinois, Stany Zjednoczone, 61832
- Carle at The Riverfront
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DeKalb, Illinois, Stany Zjednoczone, 60115
- Northwestern Medicine Cancer Center Kishwaukee
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Effingham, Illinois, Stany Zjednoczone, 62401
- Carle Physician Group-Effingham
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Geneva, Illinois, Stany Zjednoczone, 60134
- Northwestern Medicine Cancer Center Delnor
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Grayslake, Illinois, Stany Zjednoczone, 60030
- Northwestern Medicine Grayslake Outpatient Center
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Lake Forest, Illinois, Stany Zjednoczone, 60045
- Northwestern Medicine Lake Forest Hospital
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Mattoon, Illinois, Stany Zjednoczone, 61938
- Carle Physician Group-Mattoon/Charleston
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Orland Park, Illinois, Stany Zjednoczone, 60462
- Northwestern Medicine Orland Park
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Urbana, Illinois, Stany Zjednoczone, 61801
- Carle Cancer Center
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Warrenville, Illinois, Stany Zjednoczone, 60555
- Northwestern Medicine Cancer Center Warrenville
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Indiana
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Indianapolis, Indiana, Stany Zjednoczone, 46260
- Ascension Saint Vincent Indianapolis Hospital
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Iowa
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Iowa City, Iowa, Stany Zjednoczone, 52242
- University of Iowa/Holden Comprehensive Cancer Center
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Maine
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Scarborough, Maine, Stany Zjednoczone, 04074
- MaineHealth Maine Medical Center- Scarborough
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Michigan
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Ann Arbor, Michigan, Stany Zjednoczone, 48109
- University of Michigan Rogel Cancer Center
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Ann Arbor, Michigan, Stany Zjednoczone, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
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Battle Creek, Michigan, Stany Zjednoczone, 49017
- Bronson Battle Creek
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Brighton, Michigan, Stany Zjednoczone, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
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Canton, Michigan, Stany Zjednoczone, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
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Chelsea, Michigan, Stany Zjednoczone, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
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Flint, Michigan, Stany Zjednoczone, 48503
- Hurley Medical Center
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Flint, Michigan, Stany Zjednoczone, 48503
- Genesee Hematology Oncology PC
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Flint, Michigan, Stany Zjednoczone, 48503
- Genesys Hurley Cancer Institute
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Flint, Michigan, Stany Zjednoczone, 48503
- Cancer Hematology Centers - Flint
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Grand Rapids, Michigan, Stany Zjednoczone, 49503
- Trinity Health Grand Rapids Hospital
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Grand Rapids, Michigan, Stany Zjednoczone, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
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Kalamazoo, Michigan, Stany Zjednoczone, 49007
- West Michigan Cancer Center
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Kalamazoo, Michigan, Stany Zjednoczone, 49007
- Bronson Methodist Hospital
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Kalamazoo, Michigan, Stany Zjednoczone, 49009
- Beacon Kalamazoo Cancer Center
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Livonia, Michigan, Stany Zjednoczone, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
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Muskegon, Michigan, Stany Zjednoczone, 49444
- Trinity Health Muskegon Hospital
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Norton Shores, Michigan, Stany Zjednoczone, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
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Reed City, Michigan, Stany Zjednoczone, 49677
- Corewell Health Reed City Hospital
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Saint Joseph, Michigan, Stany Zjednoczone, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
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Traverse City, Michigan, Stany Zjednoczone, 49684
- Munson Medical Center
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Wyoming, Michigan, Stany Zjednoczone, 49519
- University of Michigan Health - West
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Ypsilanti, Michigan, Stany Zjednoczone, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
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Missouri
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St Louis, Missouri, Stany Zjednoczone, 63141
- Mercy Hospital Saint Louis
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Montana
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Anaconda, Montana, Stany Zjednoczone, 59711
- Community Hospital of Anaconda
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Billings, Montana, Stany Zjednoczone, 59101
- Billings Clinic Cancer Center
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Bozeman, Montana, Stany Zjednoczone, 59715
- Bozeman Health Deaconess Hospital
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Great Falls, Montana, Stany Zjednoczone, 59405
- Benefis Sletten Cancer Institute
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Missoula, Montana, Stany Zjednoczone, 59804
- Community Medical Center
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Nebraska
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Omaha, Nebraska, Stany Zjednoczone, 68198
- University of Nebraska Medical Center
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North Carolina
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Charlotte, North Carolina, Stany Zjednoczone, 28203
- Carolinas Medical Center/Levine Cancer Institute
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Concord, North Carolina, Stany Zjednoczone, 28025
- Atrium Health Cabarrus/LCI-Concord
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Ohio
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Centerville, Ohio, Stany Zjednoczone, 45459
- Miami Valley Hospital South
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Cleveland, Ohio, Stany Zjednoczone, 44195
- Cleveland Clinic Foundation
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Sylvania, Ohio, Stany Zjednoczone, 43560
- ProMedica Flower Hospital
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Oklahoma
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Oklahoma City, Oklahoma, Stany Zjednoczone, 73104
- University of Oklahoma Health Sciences Center
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Oregon
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Ontario, Oregon, Stany Zjednoczone, 97914
- Saint Alphonsus Cancer Care Center-Ontario
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Portland, Oregon, Stany Zjednoczone, 97210
- Legacy Good Samaritan Hospital and Medical Center
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Tualatin, Oregon, Stany Zjednoczone, 97062
- Legacy Meridian Park Hospital
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Washington
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Vancouver, Washington, Stany Zjednoczone, 98686
- Legacy Salmon Creek Hospital
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West Virginia
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Charleston, West Virginia, Stany Zjednoczone, 25304
- West Virginia University Charleston Division
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Wisconsin
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Appleton, Wisconsin, Stany Zjednoczone, 54911
- ThedaCare Regional Cancer Center
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Milwaukee, Wisconsin, Stany Zjednoczone, 53226
- Medical College of Wisconsin
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Kryteria uczestnictwa
Kryteria kwalifikacji
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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
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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 studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nie dotyczy
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Liczba ramion
Broń i interwencje
Grupa uczestników / ArmGrupa uczestników / Arm |
Interwencja / LeczenieInterwencja / Leczenie |
|---|---|
|
Eksperymentalny: 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
Inne nazwy:
Undergo MRI
Inne nazwy:
Undergo PET/CT
Inne nazwy:
Undergo chest x-ray
Inne nazwy:
Undergo CT and/or PET/CT
Inne nazwy:
Given PO
Inne nazwy:
Undergo archived tissue and blood sample collection
Inne nazwy:
Given IM
Inne nazwy:
|
Co mierzy badanie?
Podstawowe miary wyniku
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
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Objective Response Rate (ORR)
Ramy czasowe: 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
|
Miary wyników drugorzędnych
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Duration of Response
Ramy czasowe: 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)
Ramy czasowe: 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)
Ramy czasowe: 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
|
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Incidence of Adverse Events
Ramy czasowe: 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.
|
Współpracownicy i badacze
Sponsor
Sponsor
Współpracownicy
Współpracownicy
Śledczy
Śledczy
- Główny śledczy: Elizabeth Hopp, NRG Oncology
Publikacje i pomocne linki
Publikacje ogólne
- 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.
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Rzeczywisty)
Rozpoczęcie studiów
Zakończenie podstawowe (Rzeczywisty)
Zakończenie podstawowe
Ukończenie studiów (Rzeczywisty)
Ukończenie studiów
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Pierwszy wysłany
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia wysłana aktualizacja
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
- Guz komórkowy granulosa jajnika
- Hormony
- Hormony, substytuty hormonów i antagoniści hormonów
- Hormony uwalniające hormony przysadki
- Hormony podwzgórza
- Hormony peptydowe
- Neuropeptydy
- Peptydy
- Aminokwasy, peptydy i białka
- Oligopeptydy
- Białka tkanek nerwowych
- Białka
- Techniki śledcze
- Techniki laboratoryjne kliniczne
- Techniki i procedury diagnostyczne
- Diagnoza
- Zjawiska fizyczne
- Techniki chemii, analityczne
- Analiza widma
- Zjawiska elektromagnetyczne
- Zjawiska magnetyczne
- Promieniowanie elektromagnetyczne
- Promieniowanie
- Promieniowanie, jonizujące
- Hormon uwalniający gonadotropinę
- Leuprolid
- składnik żelowy
- darlutamid
- Prowadzenie okazów
- Spektroskopia rezonansu magnetycznego
- Promieniowanie rentgenowskie
- przykład
Inne numery identyfikacyjne badania
Inne numery identyfikacyjne badania
- NCI-2023-06524
- U10CA180868 (Grant/umowa NIH USA)
- NCI-2023-06524 (Identyfikator rejestru: CTRP (Clinical Trial Reporting Program))
- NRG-GY033 (Inny identyfikator: CTEP)
- NRG-GY033 (Inny identyfikator: NRG Oncology)
Plan dla danych uczestnika indywidualnego (IPD)
Planujesz udostępniać dane poszczególnych uczestników (IPD)?
Opis planu 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.
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
Te informacje zostały pobrane bezpośrednio ze strony internetowej clinicaltrials.gov bez żadnych zmian. Jeśli chcesz zmienić, usunąć lub zaktualizować dane swojego badania, skontaktuj się z register@clinicaltrials.gov. Gdy tylko zmiana zostanie wprowadzona na stronie clinicaltrials.gov, zostanie ona automatycznie zaktualizowana również na naszej stronie internetowej .