Studie for å teste stoffet darolutamid sammen med stoffene leuprolidacetat og eksemestan hos pasienter med tilbakevendende ovariegranulosacellesvulster
En fase II-studie av hemming av androgenreseptor (AR) av darolutamid i kombinasjon med leuprolidacetat og eksemestan i tilbakevendende 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.
Studieoversikt
Status
Detaljert 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.
Studietype
Registrering (Faktiske)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
-
-
California
-
Los Angeles, California, Forente stater, 90048
- Cedars-Sinai Medical Center
-
-
Delaware
-
Newark, Delaware, Forente stater, 19713
- Helen F Graham Cancer Center
-
Newark, Delaware, Forente stater, 19713
- Medical Oncology Hematology Consultants PA
-
-
Idaho
-
Boise, Idaho, Forente stater, 83706
- Saint Alphonsus Cancer Care Center-Boise
-
Caldwell, Idaho, Forente stater, 83605
- Saint Alphonsus Cancer Care Center-Caldwell
-
Coeur d'Alene, Idaho, Forente stater, 83814
- Kootenai Health - Coeur d'Alene
-
Nampa, Idaho, Forente stater, 83687
- Saint Alphonsus Cancer Care Center-Nampa
-
Post Falls, Idaho, Forente stater, 83854
- Kootenai Clinic Cancer Services - Post Falls
-
Sandpoint, Idaho, Forente stater, 83864
- Kootenai Clinic Cancer Services - Sandpoint
-
-
Illinois
-
Chicago, Illinois, Forente stater, 60611
- Northwestern University
-
Danville, Illinois, Forente stater, 61832
- Carle at The Riverfront
-
DeKalb, Illinois, Forente stater, 60115
- Northwestern Medicine Cancer Center Kishwaukee
-
Effingham, Illinois, Forente stater, 62401
- Carle Physician Group-Effingham
-
Geneva, Illinois, Forente stater, 60134
- Northwestern Medicine Cancer Center Delnor
-
Grayslake, Illinois, Forente stater, 60030
- Northwestern Medicine Grayslake Outpatient Center
-
Lake Forest, Illinois, Forente stater, 60045
- Northwestern Medicine Lake Forest Hospital
-
Mattoon, Illinois, Forente stater, 61938
- Carle Physician Group-Mattoon/Charleston
-
Orland Park, Illinois, Forente stater, 60462
- Northwestern Medicine Orland Park
-
Urbana, Illinois, Forente stater, 61801
- Carle Cancer Center
-
Warrenville, Illinois, Forente stater, 60555
- Northwestern Medicine Cancer Center Warrenville
-
-
Indiana
-
Indianapolis, Indiana, Forente stater, 46260
- Ascension Saint Vincent Indianapolis Hospital
-
-
Iowa
-
Iowa City, Iowa, Forente stater, 52242
- University of Iowa/Holden Comprehensive Cancer Center
-
-
Maine
-
Scarborough, Maine, Forente stater, 04074
- MaineHealth Maine Medical Center- Scarborough
-
-
Michigan
-
Ann Arbor, Michigan, Forente stater, 48109
- University of Michigan Rogel Cancer Center
-
Ann Arbor, Michigan, Forente stater, 48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
-
Battle Creek, Michigan, Forente stater, 49017
- Bronson Battle Creek
-
Brighton, Michigan, Forente stater, 48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
-
Canton, Michigan, Forente stater, 48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
-
Chelsea, Michigan, Forente stater, 48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
-
Flint, Michigan, Forente stater, 48503
- Hurley Medical Center
-
Flint, Michigan, Forente stater, 48503
- Genesee Hematology Oncology PC
-
Flint, Michigan, Forente stater, 48503
- Genesys Hurley Cancer Institute
-
Flint, Michigan, Forente stater, 48503
- Cancer Hematology Centers - Flint
-
Grand Rapids, Michigan, Forente stater, 49503
- Trinity Health Grand Rapids Hospital
-
Grand Rapids, Michigan, Forente stater, 49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
-
Kalamazoo, Michigan, Forente stater, 49007
- West Michigan Cancer Center
-
Kalamazoo, Michigan, Forente stater, 49007
- Bronson Methodist Hospital
-
Kalamazoo, Michigan, Forente stater, 49009
- Beacon Kalamazoo Cancer Center
-
Livonia, Michigan, Forente stater, 48154
- Trinity Health Saint Mary Mercy Livonia Hospital
-
Muskegon, Michigan, Forente stater, 49444
- Trinity Health Muskegon Hospital
-
Norton Shores, Michigan, Forente stater, 49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
-
Reed City, Michigan, Forente stater, 49677
- Corewell Health Reed City Hospital
-
Saint Joseph, Michigan, Forente stater, 49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
-
Traverse City, Michigan, Forente stater, 49684
- Munson Medical Center
-
Wyoming, Michigan, Forente stater, 49519
- University of Michigan Health - West
-
Ypsilanti, Michigan, Forente stater, 48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
-
-
Missouri
-
St Louis, Missouri, Forente stater, 63141
- Mercy Hospital Saint Louis
-
-
Montana
-
Anaconda, Montana, Forente stater, 59711
- Community Hospital of Anaconda
-
Billings, Montana, Forente stater, 59101
- Billings Clinic Cancer Center
-
Bozeman, Montana, Forente stater, 59715
- Bozeman Health Deaconess Hospital
-
Great Falls, Montana, Forente stater, 59405
- Benefis Sletten Cancer Institute
-
Missoula, Montana, Forente stater, 59804
- Community Medical Center
-
-
Nebraska
-
Omaha, Nebraska, Forente stater, 68198
- University of Nebraska Medical Center
-
-
North Carolina
-
Charlotte, North Carolina, Forente stater, 28203
- Carolinas Medical Center/Levine Cancer Institute
-
Concord, North Carolina, Forente stater, 28025
- Atrium Health Cabarrus/LCI-Concord
-
-
Ohio
-
Centerville, Ohio, Forente stater, 45459
- Miami Valley Hospital South
-
Cleveland, Ohio, Forente stater, 44195
- Cleveland Clinic Foundation
-
Sylvania, Ohio, Forente stater, 43560
- ProMedica Flower Hospital
-
-
Oklahoma
-
Oklahoma City, Oklahoma, Forente stater, 73104
- University of Oklahoma Health Sciences Center
-
-
Oregon
-
Ontario, Oregon, Forente stater, 97914
- Saint Alphonsus Cancer Care Center-Ontario
-
Portland, Oregon, Forente stater, 97210
- Legacy Good Samaritan Hospital and Medical Center
-
Tualatin, Oregon, Forente stater, 97062
- Legacy Meridian Park Hospital
-
-
Washington
-
Vancouver, Washington, Forente stater, 98686
- Legacy Salmon Creek Hospital
-
-
West Virginia
-
Charleston, West Virginia, Forente stater, 25304
- West Virginia University Charleston Division
-
-
Wisconsin
-
Appleton, Wisconsin, Forente stater, 54911
- ThedaCare Regional Cancer Center
-
Milwaukee, Wisconsin, Forente stater, 53226
- Medical College of Wisconsin
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
-
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
-
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: N/A
- Intervensjonsmodell: Enkeltgruppeoppdrag
- Masking: Ingen (Open Label)
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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 navn:
Undergo MRI
Andre navn:
Undergo PET/CT
Andre navn:
Undergo chest x-ray
Andre navn:
Undergo CT and/or PET/CT
Andre navn:
Given PO
Andre navn:
Undergo archived tissue and blood sample collection
Andre navn:
Given IM
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
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
Resultatmål |
Tiltaksbeskrivelse |
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.
|
Samarbeidspartnere og etterforskere
Sponsor
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Elizabeth Hopp, NRG Oncology
Publikasjoner og nyttige lenker
Generelle publikasjoner
- 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.
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Faktiske)
Studiet fullført (Faktiske)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Granulosa celletumor i eggstokken
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Humofyshormonfrigjørende hormoner
- Hypotalamiske hormoner
- Peptidhormoner
- Nevropeptider
- Peptider
- Aminosyrer, peptider og proteiner
- Oligopeptider
- Nervevevsproteiner
- Proteiner
- Undersøkelsesteknikker
- Kliniske laboratorieteknikker
- Diagnostiske teknikker og prosedyrer
- Diagnose
- Fysiske fenomener
- Kjemisteknikker, analytisk
- Spektrumanalyse
- Elektromagnetiske fenomener
- Magnetiske fenomener
- Elektromagnetisk stråling
- Stråling
- Stråling, ioniserende
- Gonadotropinfrigjørende hormon
- Leuprolid
- Luprolidacetatgeldepot
- darolutamid
- Prøvehåndtering
- Magnetisk resonansspektroskopi
- Røntgenbilder
- eksemestan
Andre studie-ID-numre
- NCI-2023-06524
- U10CA180868 (U.S. NIH-stipend/kontrakt)
- NCI-2023-06524 (Registeridentifikator: CTRP (Clinical Trial Reporting Program))
- NRG-GY033 (Annen identifikator: CTEP)
- NRG-GY033 (Annen identifikator: NRG Oncology)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (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.
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .