Clinical trial NCT05059236: A Study to Learn How Well Darolutamide Administered Together With Androgen Deprivation Therapy (ADT) Works in Men With Metastatic Hormone-sensitive Prostate Cancer. Results Will be Compared With ADT Alone From a Previously Conducted Study.
Official title: Open-label Study of Androgen Receptor Inhibition With dArolutamide Plus Androgen Deprivation Therapy (ADT) Versus ADT in Men With Metastatic Hormone-Sensitive Prostate Cancer Using an External Control Arm
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Metastatic Hormone-sensitive Prostate Cancer
Keywords: Metastatic hormone-sensitive prostate cancer (mHSPC)
Prostate Cancer
Darolutamide
Nubeqa
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2021-09-28
Enrollment: 223
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to assess if the addition of darolutamide to ADT compared with ADT alone would result in superior clinical efficacy in participants with metastatic hormone-sensitive prostate cancer (mHSPC) by progression-free survival.

The researchers want to learn how long it takes for the cancer to get worse (also known as "progression-free survival") by either increasing symptoms, new metastases, PSA rise or death. All participants will be on treatment and take darolutamide with ADT until their cancer spreads, they have a medical problem, or they leave the study. The results will then be compared with patients' results from another study who received ADT alone (CHAARTED).

This study will also assess safety by gathering adverse event information throughout the duration of the study. An adverse event is any medical problem, related or not to study treatment that a participant has during a study.

The study drug, darolutamide, is already available for doctors to prescribe to patients with prostate cancer that has not yet spread to other parts of the body. It works by blocking a protein called a receptor from attaching to a hormone called androgen that is found in men. This protein can also be found in prostate cancer cells. ADT is a treatment that doctors are currently able to prescribe to patients with mHSPC. ADT is used to lower the amount of the androgen hormone.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of prostate. Participants may have begun androgen-deprivation therapy (up to 120 days prior to enrollment). Note: Relugolix is not permitted as ADT in this study.
* Metastatic disease and will be stratified by presence of high volume or low volume disease.
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0, 1 or 2
* Adequate bone marrow, liver and renal function within 4 weeks of enrollment
* At least 4 weeks since prior major surgery and recovered from all toxicity from such surgery prior to enrollment
* Prior adjuvant or neoadjuvant hormonal therapy allowed provided the following criteria are met:

  * Therapy was discontinued ≥ 12 months ago AND there was a clinical state without evidence of disease at least 12 months after completing adjuvant or neoadjuvant hormonal therapy, as defined by 1 of the following:

    * PSA \< 0.1 ng/mL after prostatectomy plus hormonal therapy
    * PSA \< 0.5 ng/mL and has not doubled above nadir after radiotherapy plus hormonal therapy
  * Therapy lasted no more than 24 months
* Prior palliative radiotherapy allowed for participants, if commenced within 30 days before starting androgen deprivation.
* Bicalutamide, nilutamide or flutamide are allowed as single-agent therapy ≤ 28 days before medical castration to prevent flare.

Exclusion Criteria:

* PSA met criteria for PSA progression
* History of malignancy in the past 5 years, with the exception of basal cell and squamous cell carcinoma of the skin.
* Had any of the following within 6 months before randomization: myocardial infarction, severe/unstable angina pectoris, congestive heart failure, hospitalization for any cardiac event, including conduction abnormalities
* Pathological finding consistent with small cell, or neuroendocrine carcinoma of the prostate
* Known brain/ leptomeningeal metastases
* An active viral hepatitis (defined as Hepatitis B surface antigen \[HBsAg\] reactive or detectable \[qualitative\] HBV DNA defined as HCV Ribonucleic Acid \[RNA\] \[qualitative\] is detected), known human immunodeficiency virus infection with detectable viral load, or chronic liver disease with a need of treatment
* Uncontrolled hypertension as indicated by a resting systolic BP ≥ 160 mmHg or diastolic BP ≥ 100 mmHg despite medical management
* A gastrointestinal (GI) disorder or procedure which is expected to interfere significantly with absorption of study drug
* Any other serious or unstable illness, or medical, social, or psychological condition, that could jeopardize the safety of the participant and/or his compliance with study procedures or may interfere with the participant's participation in the study or evaluation of the study results.
* Prior hormone therapy in the metastatic setting
* Prior chemotherapy in the adjuvant or neoadjuvant setting
* Concurrent use or previous exposure of 5-alpha reductase inhibitors (within 28 days before the start of darolutamide or 5 half-lives of the drug, whichever is longer)
* Any Prior treatment with second-generation androgen receptor (AR) inhibitors such as enzalutamide, apalutamide, darolutamide, or other investigational AR inhibitors, Cytochrome P17 enzyme inhibitor such as abiraterone acetate or other investigational CYP 17 as antineoplastic treatment for prostate cancer
* Previous (within 28 days before the start of darolutamide or 5 half-lives of the investigational treatment of the previous study, whichever is longer) or concomitant participation in another clinical study with investigational medicinal product(s).
* Contraindication to both CT and MRI contrast agent
* Hypersensitivity to any of the study treatments, study treatment classes, or excipients in the formulation of the study treatments
* Inability to swallow oral medications

Primary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Approximately 12 months after end of enrollment
Secondary outcomes:
measure: Overall survival (OS)
timeFrame: Approximately 24 months after end of enrollment
measure: Radiographic Progression-free survival (rPFS)
timeFrame: Approximately 24 months after end of enrollment
measure: Time to castration-resistant prostate cancer (CRPC)
timeFrame: Approximately 12 months after end of enrollment
measure: Complete PSA response rate
timeFrame: At 6 months after first administration
measure: Number of participants with adverse events
timeFrame: From the signing of the informed consent form (ICF) until 30 (+7) days after last administration, approximately 12 months
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Urology Centers of Alabama, PC
state: Alabama
city: Tucson
country: United States
facility: Arizona Urology Specialists - Tucson - W Orange Grove
state: Arizona
city: La Jolla
country: United States
facility: University of Cal. San Diego Moores Cancer Ctr.
state: California
city: Los Angeles
country: United States
facility: Tower Urology
state: California
city: Orange
country: United States
facility: UC Irvine Health
state: California
city: Santa Monica
country: United States
facility: Providence Saint John's Cancer Institute
state: California
city: Atlanta
country: United States
facility: Brigham and Women's Hospital (BWH) - Surgery Urology
state: Georgia
city: Atlanta
country: United States
facility: Piedmont Cancer Institute - Atlanta
state: Georgia
city: Chicago
country: United States
facility: Northwestern Medicine - Urology
state: Illinois
city: Chicago
country: United States
facility: Northwestern University's Feinberg School of Medicine
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland
state: Maryland
city: Ann Arbor
country: United States
facility: VA Ann Arbor Healthcare System
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute - Detroit Headquarters
state: Michigan
city: Troy
country: United States
facility: Michigan Institute of Urology - Troy - Town Center Building
state: Michigan
city: Kansas City
country: United States
facility: AMR - Kansas City
state: Missouri
city: Omaha
country: United States
facility: GU Research Network, LLC - Oncology radiology
state: Nebraska
city: Omaha
country: United States
facility: XCancer Omaha
state: Nebraska
city: Clifton
country: United States
facility: New Jersey Urology - Clifton
state: New Jersey
city: Voorhees
country: United States
facility: New Jersey Urology - Voorhees
state: New Jersey
city: Albuquerque
country: United States
facility: New Mexico Cancer Center - Albuquerque
state: New Mexico
city: New York
country: United States
facility: Mount Sinai Doctors - Faculty Practice
state: New York
city: New York
country: United States
facility: Mount Sinai Faculty Practice Associates
state: New York
city: Syracuse
country: United States
facility: Associated Medical Professionals of NY Syracuse
state: New York
city: Cincinnati
country: United States
facility: The Urology Group
state: Ohio
city: Gahanna
country: United States
facility: Columbus Prostate Cancer Center / Radiation Oncology Clinic
state: Ohio
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology - Bala Cynwyd
state: Pennsylvania
city: Myrtle Beach
country: United States
facility: Carolina Urological Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, PC
state: Tennessee
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Spokane
country: United States
facility: Spokane Urology PS
state: Washington
Study officials:
References: