Study to Test the Drug Darolutamide Along With the Drugs Leuprolide Acetate and Exemestane in Patients With Recurrent Ovarian Granulosa Cell Tumors

Registration Number
NCT06169124
Lead Sponsor
National Cancer Institute (NCI)
Brief Summary

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 r...

Detailed Description

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:
...

Recruitment & Eligibility

Status
SUSPENDED
Sex
Female
Target Recruitment
37
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
Read More
Exclusion Criteria
  • Prior treatment with AR inhibitors
  • Known hypersensitivity to the study drugs or their ingredients
Read More

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Treatment (exemestane, darolutamide, leuprolide acetate)Computed TomographyPatients 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.
Treatment (exemestane, darolutamide, leuprolide acetate)Chest RadiographyPatients 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.
Treatment (exemestane, darolutamide, leuprolide acetate)Biospecimen CollectionPatients 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.
Treatment (exemestane, darolutamide, leuprolide acetate)Positron Emission TomographyPatients 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.
Treatment (exemestane, darolutamide, leuprolide acetate)Leuprolide AcetatePatients 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.
Treatment (exemestane, darolutamide, leuprolide acetate)Magnetic Resonance ImagingPatients 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.
Treatment (exemestane, darolutamide, leuprolide acetate)DarolutamidePatients 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.
Treatment (exemestane, darolutamide, leuprolide acetate)ExemestanePatients 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.
Primary Outcome Measures
NameTimeMethod
Objective response rateWithin 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.

Secondary Outcome Measures
NameTimeMethod
Progression-free survival (PFS)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, assessed up to 5 years

Will be graphed using Kaplan-Meier methods. Median PFS will be estimated with corresponding 95% confidence intervals.

Incidence of adverse eventsUp to 5 years

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 individual...

Duration of responseFrom the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years

Median duration of response with a corresponding 95% confidence interval will be estimated. The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented. Stable disease is measured from the start of the treatment until the criteria for progression are me...

Overall survival (OS)From study entry to time of death or the date of last contact, assessed up to 5 years

Will be graphed using Kaplan-Meier methods. Median OS will be estimated with corresponding 95% confidence intervals.

Trial Locations

Locations (67)

Cancer Hematology Centers - Flint

🇺🇸

Flint, Michigan, United States

Cedars Sinai Medical Center

🇺🇸

Los Angeles, California, United States

Helen F Graham Cancer Center

🇺🇸

Newark, Delaware, United States

Medical Oncology Hematology Consultants PA

🇺🇸

Newark, Delaware, United States

Saint Alphonsus Cancer Care Center-Boise

🇺🇸

Boise, Idaho, United States

Saint Alphonsus Cancer Care Center-Caldwell

🇺🇸

Caldwell, Idaho, United States

Kootenai Health - Coeur d'Alene

🇺🇸

Coeur d'Alene, Idaho, United States

Saint Alphonsus Cancer Care Center-Nampa

🇺🇸

Nampa, Idaho, United States

Kootenai Clinic Cancer Services - Post Falls

🇺🇸

Post Falls, Idaho, United States

Kootenai Clinic Cancer Services - Sandpoint

🇺🇸

Sandpoint, Idaho, United States

Northwestern University

🇺🇸

Chicago, Illinois, United States

Carle at The Riverfront

🇺🇸

Danville, Illinois, United States

Northwestern Medicine Cancer Center Kishwaukee

🇺🇸

DeKalb, Illinois, United States

Carle Physician Group-Effingham

🇺🇸

Effingham, Illinois, United States

Northwestern Medicine Cancer Center Delnor

🇺🇸

Geneva, Illinois, United States

Northwestern Medicine Grayslake Outpatient Center

🇺🇸

Grayslake, Illinois, United States

Northwestern Medicine Lake Forest Hospital

🇺🇸

Lake Forest, Illinois, United States

Carle Physician Group-Mattoon/Charleston

🇺🇸

Mattoon, Illinois, United States

Northwestern Medicine Orland Park

🇺🇸

Orland Park, Illinois, United States

Carle Cancer Center

🇺🇸

Urbana, Illinois, United States

Northwestern Medicine Cancer Center Warrenville

🇺🇸

Warrenville, Illinois, United States

Ascension Saint Vincent Indianapolis Hospital

🇺🇸

Indianapolis, Indiana, United States

University of Iowa/Holden Comprehensive Cancer Center

🇺🇸

Iowa City, Iowa, United States

Maine Medical Center- Scarborough Campus

🇺🇸

Scarborough, Maine, United States

Trinity Health Saint Joseph Mercy Hospital Ann Arbor

🇺🇸

Ann Arbor, Michigan, United States

University of Michigan Comprehensive Cancer Center

🇺🇸

Ann Arbor, Michigan, United States

Trinity Health Muskegon Hospital

🇺🇸

Muskegon, Michigan, United States

Cancer and Hematology Centers of Western Michigan - Norton Shores

🇺🇸

Norton Shores, Michigan, United States

Corewell Health Reed City Hospital

🇺🇸

Reed City, Michigan, United States

Bronson Battle Creek

🇺🇸

Battle Creek, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Brighton

🇺🇸

Brighton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Canton

🇺🇸

Canton, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital

🇺🇸

Chelsea, Michigan, United States

Genesee Hematology Oncology PC

🇺🇸

Flint, Michigan, United States

Genesys Hurley Cancer Institute

🇺🇸

Flint, Michigan, United States

Hurley Medical Center

🇺🇸

Flint, Michigan, United States

Corewell Health Grand Rapids Hospitals - Butterworth Hospital

🇺🇸

Grand Rapids, Michigan, United States

Trinity Health Grand Rapids Hospital

🇺🇸

Grand Rapids, Michigan, United States

Bronson Methodist Hospital

🇺🇸

Kalamazoo, Michigan, United States

West Michigan Cancer Center

🇺🇸

Kalamazoo, Michigan, United States

Ascension Borgess Cancer Center

🇺🇸

Kalamazoo, Michigan, United States

Corewell Health Lakeland Hospitals - Marie Yeager Cancer Center

🇺🇸

Saint Joseph, Michigan, United States

Trinity Health Saint Mary Mercy Livonia Hospital

🇺🇸

Livonia, Michigan, United States

Munson Medical Center

🇺🇸

Traverse City, Michigan, United States

University of Michigan Health - West

🇺🇸

Wyoming, Michigan, United States

Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus

🇺🇸

Ypsilanti, Michigan, United States

Mercy Hospital Saint Louis

🇺🇸

Saint Louis, Missouri, United States

Community Hospital of Anaconda

🇺🇸

Anaconda, Montana, United States

Billings Clinic Cancer Center

🇺🇸

Billings, Montana, United States

Bozeman Health Deaconess Hospital

🇺🇸

Bozeman, Montana, United States

Benefis Sletten Cancer Institute

🇺🇸

Great Falls, Montana, United States

Community Medical Center

🇺🇸

Missoula, Montana, United States

University of Nebraska Medical Center

🇺🇸

Omaha, Nebraska, United States

Carolinas Medical Center/Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Atrium Health Cabarrus/LCI-Concord

🇺🇸

Concord, North Carolina, United States

Miami Valley Hospital South

🇺🇸

Centerville, Ohio, United States

Cleveland Clinic Foundation

🇺🇸

Cleveland, Ohio, United States

ProMedica Flower Hospital

🇺🇸

Sylvania, Ohio, United States

University of Oklahoma Health Sciences Center

🇺🇸

Oklahoma City, Oklahoma, United States

Saint Alphonsus Cancer Care Center-Ontario

🇺🇸

Ontario, Oregon, United States

Legacy Good Samaritan Hospital and Medical Center

🇺🇸

Portland, Oregon, United States

Legacy Meridian Park Hospital

🇺🇸

Tualatin, Oregon, United States

NRG Oncology

🇺🇸

Philadelphia, Pennsylvania, United States

Legacy Salmon Creek Hospital

🇺🇸

Vancouver, Washington, United States

West Virginia University Charleston Division

🇺🇸

Charleston, West Virginia, United States

ThedaCare Regional Cancer Center

🇺🇸

Appleton, Wisconsin, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

© Copyright 2024. All Rights Reserved by MedPath