ACTIVE_NOT_RECRUITING

Testing the Anti-cancer Drug Darolutamide in Patients With Testosterone-Driven Salivary Gland Cancers

Conditions

Locally Advanced Salivary Gland Carcinoma Metastatic Salivary Gland Carcinoma Recurrent Salivary Gland Carcinoma Unresectable Salivary Gland Carcinoma

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This phase II trial tests how well darolutamide and leuprolide acetate work in treating patients with androgen receptor positive salivary cancer that has spread from where it first started (primary site) to other places in the body (metastatic), cannot be removed by surgery (unresectable) or that has come back after a period of responding to prior therapy (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 cancer cells. Leuprolide acetate is in a class of medications called gonadotropin-releasing hormone (GnRH) agonists. It works by decreasing the amount of certain hormones in the body. Giving darolutamide in combination with leuprolide acetate may help to stop the growth of tumor cells that need androgens to grow or shrink them.

Official Title

A Phase 2 Study of Darolutamide in Combination With Leuprolide Acetate in Hormone-Therapy Naive Recurrent and/or Metastatic Androgen Receptor (AR) Positive Salivary Gland Cancer

Quick Facts

Study Start:2023-07-20

Study Completion:2027-04-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05669664

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	* 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)

Inclusion Criteria

Exclusion 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

* 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)

Contacts and Locations

Principal Investigator

Alan L Ho

PRINCIPAL_INVESTIGATOR

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Study Locations (Sites)

UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care

Irvine, California, 92612

United States

Los Angeles General Medical Center

Los Angeles, California, 90033

United States

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033

United States

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868

United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817

United States

UCHealth University of Colorado Hospital

Aurora, Colorado, 80045

United States

Emory University Hospital Midtown

Atlanta, Georgia, 30308

United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637

United States

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451

United States

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462

United States

UChicago Medicine Northwest Indiana

Crown Point, Indiana, 46307

United States

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920

United States

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748

United States

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645

United States

Memorial Sloan Kettering Commack

Commack, New York, 11725

United States

Memorial Sloan Kettering Westchester

Harrison, New York, 10604

United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553

United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599

United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104

United States

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232

United States

M D Anderson Cancer Center

Houston, Texas, 77030

United States

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112

United States

University of Virginia Cancer Center

Charlottesville, Virginia, 22908

United States

University of Wisconsin Carbone Cancer Center - Eastpark Medical Center

Madison, Wisconsin, 53718

United States

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, 53792

United States

Collaborators and Investigators

Sponsor: National Cancer Institute (NCI)

Alan L Ho, PRINCIPAL_INVESTIGATOR, JHU Sidney Kimmel Comprehensive Cancer Center LAO

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-07-20

Study Completion Date2027-04-11

Study Record Updates

Study Start Date2023-07-20

Study Completion Date2027-04-11

Terms related to this study

Additional Relevant MeSH Terms

Locally Advanced Salivary Gland Carcinoma
Metastatic Salivary Gland Carcinoma
Recurrent Salivary Gland Carcinoma
Unresectable Salivary Gland Carcinoma