再発性卵巣顆粒膜細胞腫瘍患者を対象に、酢酸ロイプロリドおよびエキセメスタンと併用してダロルタミドという薬剤を試験する研究
再発成人型卵巣顆粒膜細胞腫瘍におけるダロルタミドと酢酸ロイプロリドおよびエキセメスタンの併用によるアンドロゲン受容体（AR）阻害の第II相研究
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.
調査の概要
状態
状態
条件
条件
介入・治療
介入・治療
詳細な説明
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.
研究の種類
研究の種類
入学 (実際)
入学
段階
段階
- フェーズ2
連絡先と場所
研究場所
-
-
California
-
Los Angeles、California、アメリカ、90048
- Cedars-Sinai Medical Center
-
-
Delaware
-
Newark、Delaware、アメリカ、19713
- Helen F Graham Cancer Center
-
Newark、Delaware、アメリカ、19713
- Medical Oncology Hematology Consultants PA
-
-
Idaho
-
Boise、Idaho、アメリカ、83706
- Saint Alphonsus Cancer Care Center-Boise
-
Caldwell、Idaho、アメリカ、83605
- Saint Alphonsus Cancer Care Center-Caldwell
-
Coeur d'Alene、Idaho、アメリカ、83814
- Kootenai Health - Coeur d'Alene
-
Nampa、Idaho、アメリカ、83687
- Saint Alphonsus Cancer Care Center-Nampa
-
Post Falls、Idaho、アメリカ、83854
- Kootenai Clinic Cancer Services - Post Falls
-
Sandpoint、Idaho、アメリカ、83864
- Kootenai Clinic Cancer Services - Sandpoint
-
-
Illinois
-
Chicago、Illinois、アメリカ、60611
- Northwestern University
-
Danville、Illinois、アメリカ、61832
- Carle at The Riverfront
-
DeKalb、Illinois、アメリカ、60115
- Northwestern Medicine Cancer Center Kishwaukee
-
Effingham、Illinois、アメリカ、62401
- Carle Physician Group-Effingham
-
Geneva、Illinois、アメリカ、60134
- Northwestern Medicine Cancer Center Delnor
-
Grayslake、Illinois、アメリカ、60030
- Northwestern Medicine Grayslake Outpatient Center
-
Lake Forest、Illinois、アメリカ、60045
- Northwestern Medicine Lake Forest Hospital
-
Mattoon、Illinois、アメリカ、61938
- Carle Physician Group-Mattoon/Charleston
-
Orland Park、Illinois、アメリカ、60462
- Northwestern Medicine Orland Park
-
Urbana、Illinois、アメリカ、61801
- Carle Cancer Center
-
Warrenville、Illinois、アメリカ、60555
- Northwestern Medicine Cancer Center Warrenville
-
-
Indiana
-
Indianapolis、Indiana、アメリカ、46260
- Ascension Saint Vincent Indianapolis Hospital
-
-
Iowa
-
Iowa City、Iowa、アメリカ、52242
- University of Iowa/Holden Comprehensive Cancer Center
-
-
Maine
-
Scarborough、Maine、アメリカ、04074
- MaineHealth Maine Medical Center- Scarborough
-
-
Michigan
-
Ann Arbor、Michigan、アメリカ、48109
- University of Michigan Rogel Cancer Center
-
Ann Arbor、Michigan、アメリカ、48106
- Trinity Health Saint Joseph Mercy Hospital Ann Arbor
-
Battle Creek、Michigan、アメリカ、49017
- Bronson Battle Creek
-
Brighton、Michigan、アメリカ、48114
- Trinity Health IHA Medical Group Hematology Oncology - Brighton
-
Canton、Michigan、アメリカ、48188
- Trinity Health IHA Medical Group Hematology Oncology - Canton
-
Chelsea、Michigan、アメリカ、48118
- Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
-
Flint、Michigan、アメリカ、48503
- Hurley Medical Center
-
Flint、Michigan、アメリカ、48503
- Genesee Hematology Oncology PC
-
Flint、Michigan、アメリカ、48503
- Genesys Hurley Cancer Institute
-
Flint、Michigan、アメリカ、48503
- Cancer Hematology Centers - Flint
-
Grand Rapids、Michigan、アメリカ、49503
- Trinity Health Grand Rapids Hospital
-
Grand Rapids、Michigan、アメリカ、49503
- Corewell Health Grand Rapids Hospitals - Butterworth Hospital
-
Kalamazoo、Michigan、アメリカ、49007
- West Michigan Cancer Center
-
Kalamazoo、Michigan、アメリカ、49007
- Bronson Methodist Hospital
-
Kalamazoo、Michigan、アメリカ、49009
- Beacon Kalamazoo Cancer Center
-
Livonia、Michigan、アメリカ、48154
- Trinity Health Saint Mary Mercy Livonia Hospital
-
Muskegon、Michigan、アメリカ、49444
- Trinity Health Muskegon Hospital
-
Norton Shores、Michigan、アメリカ、49444
- Cancer and Hematology Centers of Western Michigan - Norton Shores
-
Reed City、Michigan、アメリカ、49677
- Corewell Health Reed City Hospital
-
Saint Joseph、Michigan、アメリカ、49085
- Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center
-
Traverse City、Michigan、アメリカ、49684
- Munson Medical Center
-
Wyoming、Michigan、アメリカ、49519
- University of Michigan Health - West
-
Ypsilanti、Michigan、アメリカ、48197
- Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
-
-
Missouri
-
St Louis、Missouri、アメリカ、63141
- Mercy Hospital Saint Louis
-
-
Montana
-
Anaconda、Montana、アメリカ、59711
- Community Hospital of Anaconda
-
Billings、Montana、アメリカ、59101
- Billings Clinic Cancer Center
-
Bozeman、Montana、アメリカ、59715
- Bozeman Health Deaconess Hospital
-
Great Falls、Montana、アメリカ、59405
- Benefis Sletten Cancer Institute
-
Missoula、Montana、アメリカ、59804
- Community Medical Center
-
-
Nebraska
-
Omaha、Nebraska、アメリカ、68198
- University of Nebraska Medical Center
-
-
North Carolina
-
Charlotte、North Carolina、アメリカ、28203
- Carolinas Medical Center/Levine Cancer Institute
-
Concord、North Carolina、アメリカ、28025
- Atrium Health Cabarrus/LCI-Concord
-
-
Ohio
-
Centerville、Ohio、アメリカ、45459
- Miami Valley Hospital South
-
Cleveland、Ohio、アメリカ、44195
- Cleveland Clinic Foundation
-
Sylvania、Ohio、アメリカ、43560
- ProMedica Flower Hospital
-
-
Oklahoma
-
Oklahoma City、Oklahoma、アメリカ、73104
- University of Oklahoma Health Sciences Center
-
-
Oregon
-
Ontario、Oregon、アメリカ、97914
- Saint Alphonsus Cancer Care Center-Ontario
-
Portland、Oregon、アメリカ、97210
- Legacy Good Samaritan Hospital and Medical Center
-
Tualatin、Oregon、アメリカ、97062
- Legacy Meridian Park Hospital
-
-
Washington
-
Vancouver、Washington、アメリカ、98686
- Legacy Salmon Creek Hospital
-
-
West Virginia
-
Charleston、West Virginia、アメリカ、25304
- West Virginia University Charleston Division
-
-
Wisconsin
-
Appleton、Wisconsin、アメリカ、54911
- ThedaCare Regional Cancer Center
-
Milwaukee、Wisconsin、アメリカ、53226
- Medical College of Wisconsin
-
-
参加基準
適格基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
アーム数
武器と介入
参加者グループ / アーム参加者グループ / アーム |
介入・治療介入・治療 |
|---|---|
|
実験的：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
他の名前：
Undergo MRI
他の名前：
Undergo PET/CT
他の名前：
Undergo chest x-ray
他の名前：
Undergo CT and/or PET/CT
他の名前：
Given PO
他の名前：
Undergo archived tissue and blood sample collection
他の名前：
Given IM
他の名前：
|
この研究は何を測定していますか？
主要な結果の測定
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Objective Response Rate (ORR)
時間枠：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
|
二次結果の測定
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Duration of Response
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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.
|
協力者と研究者
捜査官
捜査官
- 主任研究者：Elizabeth Hopp、NRG Oncology
出版物と役立つリンク
一般刊行物
- 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.
研究記録日
主要日程の研究
研究開始 (実際)
研究開始
一次修了 (実際)
一次修了
研究の完了 (実際)
研究の完了
試験登録日
最初に提出
最初に提出
QC基準を満たした最初の提出物
QC基準を満たした最初の提出物
最初の投稿 (実際)
最初の投稿
学習記録の更新
投稿された最後の更新 (実際)
投稿された最後の更新
QC基準を満たした最後の更新が送信されました
QC基準を満たした最後の更新が送信されました
最終確認日
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
その他の研究ID番号
- NCI-2023-06524
- U10CA180868 (米国 NIH グラント/契約)
- NCI-2023-06524 (レジストリ識別子：CTRP (Clinical Trial Reporting Program))
- NRG-GY033 (その他の識別子：CTEP)
- NRG-GY033 (その他の識別子：NRG Oncology)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
IPD プランの説明
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.
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。