- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05669664
Testing the Anti-Cancer Drug Darolutamide in Patients With Testosterone-driven Salivary Gland Cancers
A Phase 2 Study of Darolutamide in Combination With Leuprolide Acetate in Hormone-Therapy Naïve Recurrent and/or Metastatic Androgen Receptor (AR) Positive Salivary Gland Cancer
Study Overview
Status
Conditions
Detailed Description
PRIMARY OBJECTIVE:
I. To evaluate the best overall response rate (BOR) of recurrent/metastatic androgen receptor positive (AR+) salivary gland cancer (SGC) patients within one year of darolutamide and androgen deprivation therapy (ADT).
SECONDARY OBJECTIVES:
I. To evaluate progression-free survival (PFS). II. To evaluate overall survival (OS). III. To evaluate toxicity by Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
EXPLORATORY OBJECTIVES:
I. To evaluate molecular, genomic and transcriptomic biomarkers in serial research biopsies obtained before and on darolutamide and ADT.
II. To evaluate the differences in BOR, PFS, OS with darolutamide and ADT treatment among patients who did and did not receive prior systemic therapy for AR+ SGC.
OUTLINE:
Patients receive darolutamide orally (PO) twice daily (BID) on days 1-28 of each cycle and leuprolide acetate intramuscularly (IM) every 4 or 12 weeks. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo biopsy, collection of blood samples, and computed tomography (CT)/magnetic resonance imaging (MRI) throughout the trial.
After completion of study treatment, patients are followed every 3-6 months for 2 years after treatment discontinuation or until death, whichever occurs first.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Los Angeles, California, United States, 90033
- Recruiting
- USC / Norris Comprehensive Cancer Center
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Contact:
- Site Public Contact
- Phone Number: 323-865-0451
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Principal Investigator:
- Jacob S. Thomas
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Los Angeles, California, United States, 90033
- Recruiting
- Los Angeles General Medical Center
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Principal Investigator:
- Jacob S. Thomas
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Contact:
- Site Public Contact
- Phone Number: 323-865-0451
- Email: uscnorrisinfo@med.usc.edu
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Colorado
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Aurora, Colorado, United States, 80045
- Recruiting
- UCHealth University of Colorado Hospital
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Principal Investigator:
- Daniel W. Bowles
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Contact:
- Site Public Contact
- Phone Number: 720-848-0650
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Georgia
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Atlanta, Georgia, United States, 30308
- Recruiting
- Emory University Hospital Midtown
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Contact:
- Site Public Contact
- Phone Number: 888-946-7447
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Principal Investigator:
- Conor E. Steuer
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New Jersey
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Basking Ridge, New Jersey, United States, 07920
- Recruiting
- Memorial Sloan Kettering Basking Ridge
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Principal Investigator:
- Alan L. Ho
-
Contact:
- Site Public Contact
- Phone Number: 212-639-7592
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Middletown, New Jersey, United States, 07748
- Recruiting
- Memorial Sloan Kettering Monmouth
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Principal Investigator:
- Alan L. Ho
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Contact:
- Site Public Contact
- Phone Number: 212-639-7592
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Montvale, New Jersey, United States, 07645
- Recruiting
- Memorial Sloan Kettering Bergen
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Principal Investigator:
- Alan L. Ho
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Contact:
- Site Public Contact
- Phone Number: 212-639-7592
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New York
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Commack, New York, United States, 11725
- Recruiting
- Memorial Sloan Kettering Commack
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Principal Investigator:
- Alan L. Ho
-
Contact:
- Site Public Contact
- Phone Number: 212-639-7592
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Harrison, New York, United States, 10604
- Recruiting
- Memorial Sloan Kettering Westchester
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Principal Investigator:
- Alan L. Ho
-
Contact:
- Site Public Contact
- Phone Number: 212-639-7592
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New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center
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Principal Investigator:
- Alan L. Ho
-
Contact:
- Site Public Contact
- Phone Number: 212-639-7592
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New York, New York, United States, 10016
- Recruiting
- Laura and Isaac Perlmutter Cancer Center at NYU Langone
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Contact:
- Site Public Contact
- Email: CancerTrials@nyulangone.org
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Principal Investigator:
- Zujun Li
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Uniondale, New York, United States, 11553
- Recruiting
- Memorial Sloan Kettering Nassau
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Principal Investigator:
- Alan L. Ho
-
Contact:
- Site Public Contact
- Phone Number: 212-639-7592
-
-
North Carolina
-
Chapel Hill, North Carolina, United States, 27599
- Recruiting
- UNC Lineberger Comprehensive Cancer Center
-
Contact:
- Site Public Contact
- Phone Number: 877-668-0683
- Email: cancerclinicaltrials@med.unc.edu
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Principal Investigator:
- Shetal Patel
-
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- Recruiting
- University of Oklahoma Health Sciences Center
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Contact:
- Site Public Contact
- Phone Number: 405-271-8777
- Email: ou-clinical-trials@ouhsc.edu
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Principal Investigator:
- Minh Phan
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Pennsylvania
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Pittsburgh, Pennsylvania, United States, 15232
- Recruiting
- University of Pittsburgh Cancer Institute (UPCI)
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Contact:
- Site Public Contact
- Phone Number: 412-647-8073
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Principal Investigator:
- Dan P. Zandberg
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Texas
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Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
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Principal Investigator:
- Renata Ferrarotto
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Contact:
- Site Public Contact
- Phone Number: 877-632-6789
- Email: askmdanderson@mdanderson.org
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Utah
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Salt Lake City, Utah, United States, 84112
- Recruiting
- Huntsman Cancer Institute/University of Utah
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Contact:
- Site Public Contact
- Phone Number: 888-424-2100
- Email: cancerinfo@hci.utah.edu
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Principal Investigator:
- Jeffery S. Russell
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-
Virginia
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Charlottesville, Virginia, United States, 22908
- Recruiting
- University of Virginia Cancer Center
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Principal Investigator:
- Varinder Kaur
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Contact:
- Site Public Contact
- Phone Number: 434-243-6303
- Email: uvacancertrials@hscmail.mcc.virginia.edu
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Wisconsin
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Madison, Wisconsin, United States, 53792
- Recruiting
- University of Wisconsin Carbone Cancer Center
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Principal Investigator:
- Justine Yang-Bruce
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Contact:
- Site Public Contact
- Phone Number: 800-622-8922
- Email: clinicaltrials@cancer.wisc.edu
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed salivary gland cancer that is recurrent/metastatic or unresectable/locally advanced, with AR expression detected by immunohistochemistry (IHC) on a Clinical Laboratory Improvement Act (CLIA)-approved assay. Androgen receptor testing by immunohistochemistry (IHC) can be performed locally in a CLIA (Clinical Laboratory Improvement Amendments) certified lab
- Patients must have measurable disease
- Patients must have not had prior AR-targeted therapy, except for AR-targeted therapy administered in the neoadjuvant and/or adjuvant setting and with disease recurrence more than 6 months since treatment completion
- Age >= 18 years. Because no dosing or adverse event data are currently available on the use of darolutamide in combination with leuprolide acetate in patients < 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (exception: patients with elevated bilirubin due to Gilbert's disease would be eligible for the trial)
- Aspartate aminotransferase (AST) (serum (glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase ([SGPT]) =< 3 x institutional ULN
- Creatinine =< 1.5 x institutional ULN
- Glomerular filtration rate (GFR) >= 30 mL/min/1.73 m^2 (by Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI])
- Human immunodeficiency virus (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 treated brain metastases are eligible
- 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
- 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
- The effects of darolutamide 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 (leuprolide-acetate), women of child-bearing potential and men must agree to use adequate contraception (non-hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 7 days after completion of darolutamide administration or after the depot interval for the leuprolide-acetate dose used has been completed, whichever is longer
- Ability to understand and the willingness to sign a written informed consent document
Patients must have tumors that are safely accessible for biopsy.
- Note: Two research biopsies are mandated in this trial. If the biopsy is deemed to be unsafe after attempting the first biopsy, the patient will remain eligible for the trial and subsequent tumor biopsies will not be required
Exclusion Criteria:
- Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia and peripheral neuropathy
- Patients with a vascular or ischemic event within 6 months of study registration
- Patients who are receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to darolutamide or leuprolide acetate
- Patients on combined P-gp and strong or moderate CYP3A inducers or BCRP substrates are excluded. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
- Patients with uncontrolled intercurrent illness
- Pregnant women are excluded from this study because darolutamide is an androgen receptor inhibitor agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with darolutamide and leuprolide-acetate, breastfeeding should be discontinued if the mother is treated with darolutamide and leuprolide-acetate. These potential risks may also apply to other agents used in this study.
- Patients with moderate hepatic impairment (Child-Pugh Class B or C)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (darolutamide, leuprolide acetate)
Patients receive darolutamide PO BID on days 1-28 of each cycle and leuprolide acetate IM every 4 or 12 weeks.
Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients also undergo biopsy, collection of blood samples, and CT/MRI throughout the trial.
|
Undergo collection of blood
Other Names:
Undergo MRI
Other Names:
Undergo CT
Other Names:
Undergo biopsy
Other Names:
Given IM
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Best overall response (BOR)
Time Frame: Within 1 year of initiating treatment
|
The trial will be considered positive if 8 or more complete response/partial response are observed in stage 1 and stage 2 combined.
|
Within 1 year of initiating treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of adverse events (AEs)
Time Frame: Up to 2 years
|
Will be listed individually per patient according to Common Terminology Criteria for Adverse Events version 5.0, and the number of patients experiencing each AE will be summarized.
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Up to 2 years
|
Progression-free survival (PFS)
Time Frame: From day 1 of treatment until progression or death, assessed up to 2 years
|
Will be estimated using Kaplan-Meier methodology.
Patients without an event (progression, death) will be censored at the time of last follow-up or last day known to be alive.
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From day 1 of treatment until progression or death, assessed up to 2 years
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Overall survival (OS)
Time Frame: From day 1 of treatment until progression or death, assessed up to 2 years
|
Will be estimated using Kaplan-Meier methodology.
Patients without an event (progression, death) will be censored at the time of last follow-up or last day known to be alive.
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From day 1 of treatment until progression or death, assessed up to 2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Molecular, genomic, and transcriptomic biomarkers
Time Frame: Up to 2 years
|
Will be summarized by descriptive statistics, including mean, median and standard deviation for continuous biomarker data and frequency (%) for categorical data.
Differences in a biomarker at baseline, on treatment, and change between those two time points amongst responders and non-responders will be compared using Fisher's exact tests for categorical biomarker data and Wilcoxon Rank-Sum tests for continuous biomarker data.
In addition, a Cox proportional hazards model will be used to explore the prognostic relationship for these biomarkers measured at baseline and PFS and OS.
|
Up to 2 years
|
Differences in BOR, PFS, OS in patients who did and did not receive prior systemic therapy for androgen receptor positive salivary gland cancer
Time Frame: Up to 2 years
|
The BOR, PFS, and OS with darolutamide plus androgen deprivation therapy in patients with and without prior systemic therapies for recurrent/metastatic/unresectable disease will be compared using Fisher's exact for binary outcome and log-rank test for time-to-events outcomes.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Alan L Ho, JHU Sidney Kimmel Comprehensive Cancer Center LAO
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Head and Neck Neoplasms
- Stomatognathic Diseases
- Mouth Diseases
- Salivary Gland Diseases
- Mouth Neoplasms
- Carcinoma
- Salivary Gland Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Hormone Antagonists
- Reproductive Control Agents
- Fertility Agents, Female
- Fertility Agents
- Leuprolide
- Androgen Antagonists
Other Study ID Numbers
- NCI-2022-10701 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- UM1CA186691 (U.S. NIH Grant/Contract)
- 10553 (Other Identifier: CTEP)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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