Study to Compare the Effects of Drug Darolutamide and Drug Enzalutamide on Physical Function, Including Balance and Daily Activity, in Patients With Castration-resistant Prostate Cancer (CRPC)

NCT04157088 | Terminated Phase 2 Results FDA Drug

• 1 other identifier: 20609
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

Researchers in this study want to compare the effects of drug darolutamide and drug enzalutamide on physical function, including balance and daily activity, in patients with castration-resistant prostate cancer (CRPC). Both darolutamide and enzalutamide are approved AR inhibitors used for the treatment of patients with CRPC. AR inhibitor is a substance that keeps androgens (male sex hormones) from binding to proteins called androgen receptors, which are found in normal prostate cells, some prostate cancer cells, and in some other cells. Preventing this binding blocks the effects of these hormones in the body and therefore keeps prostate cancer cells from growing. Patients participating this study will receive either darolutamide or enzalutamide tablets. To evaluate the physical function, patients will be asked to make some movements like rising from a chair, walking three meters, etc. Additionally, researchers also want to find out the survival of patients and if patients have fatigue (feeling tired), cognitive (learning and thinking) problems, or other medical problems during the trial. Brand name of darolutamide is Nubeqa; brand name of enzalutamide is Xtandi.

Conditions

Prostatic Cancer, Castration-Resistant

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Worsening in TUG Time During the 24- Week Period.

  TUG: Timed Up \& Go. Worsening is defined as an increase of at least 1 second in TUG time from baseline. (The minimum clinically important difference \[MCID\] in TUG time is 1 second

  Up to 24 weeks

Secondary Outcomes (19)

• Number of Participants With an Increase of at Least 1 Second in TUG Time at 12 and 24 Weeks and During the 52 Weeks.

  At 12 week, 24 week and 52 week.

• Time to Worsening (Increase of at Least 1 Second) in TUG Time

  From randomization to the first date a participant had a worsening.

• Number of Participants With a Worsening in SPPB Total Score at 12 and 24 Weeks and During the 24 Weeks and 52 Weeks From Baseline.

  At 12 and 24 weeks and during the 24 weeks and 52 weeks from baseline

• Mean Change From Baseline in Daily Physical Activity as Assessed by CPM, at 12 and 24 Weeks, and During the 24 Weeks and 52 Weeks From Baseline.

  At 12 week, 24 week and 52 week

• Mean Change From Baseline in Accelerometer-assessed Proportion of Time Spent in Light to Vigorous Physical Activity Based on a Threshold of >100 Activity Counts Per Minute.

  At 12, 24, and 52 weeks for the randomization phase

Study Arms (2)

Participants treated with darolutamide

EXPERIMENTAL

Drug: Darolutamide (Nubeqa, BAY1841788)

Participants treated with enzalutamide

EXPERIMENTAL

Drug: Enzalutamide

Interventions

Darolutamide (Nubeqa, BAY1841788) DRUG

600mg, twice daily

Participants treated with darolutamide

Enzalutamide DRUG

160mg, once daily

Participants treated with enzalutamide

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 18 years of age inclusive or older at the time of signing the informed consent.
• Participants who have:
• Histologically or cytologically confirmed adenocarcinoma of prostate, CRPC (Castration-resistant prostate cancer) defined by disease progression despite ADT (Androgen deprivation therapy) and may present as either a confirmed rise in serum PSA (Prostate-specific antigen) levels (as defined by PCWG3 (Prostate Cancer Working Group)), the progression of pre-existing disease, and/or the appearance of new metastases. Metastatic and non-metastatic CRPC patients will be eligible.
• KPS (Karnofsky Performance Scale) performance status of ≥80
• Blood counts at screening: hemoglobin ≥9.0 g/dL, absolute neutrophil count ≥1500/μL, platelet count ≥100,000/μL
• Screening values of serum alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN), total bilirubin ≤1.5 × ULN, creatinine ≤2.0 × ULN
• Life expectancy of at least 1 year
• Sex: Male

You may not qualify if:

• Symptomatic local-regional disease that requires medical intervention including moderate/severe urinary obstruction or hydronephrosis with abnormal renal function due to prostate cancer. Participants with visceral metastasis will be excluded.
• Past (within 6 months before the start of study intervention) or concurrent stroke, myocardial infarction, severe/unstable angina pectoris, coronary/peripheral artery bypass graft, and/or congestive heart failure (New York Heart Association Class III or IV)
• Prior malignancy. Adequately treated basal cell or squamous cell carcinoma of the skin or superficial bladder cancer that has not spread behind the connective tissue layer (i.e. pTis, pTa, and pT1) is allowed, as well as any other cancer for which treatment has been completed 3 years before the start of study intervention and from which the participant has been disease free
• Prior or concurrent central nervous system disease, such as epilepsy, Parkinson's disease, Alzheimer's disease, dementia, or multiple sclerosis
• Non-ambulatory participants who need a wheelchair. Other assistive devices (e.g., cane or walker) are permitted.
• Clinically significant limitations in cognitive function and/or physical function, such as \>20 seconds in the TUG assessment
• Prior treatment with any of the following:
• Second-generation AR inhibitors, such as enzalutamide, apalutamide, or Darolutamide
• Other investigational AR inhibitors
• Progression on abiraterone acetate and discontinuation within 6 months before signing the ICF for the study
• Use of immunotherapy within 28 days before the start of study intervention
• Treatment with radiotherapy/radiopharmaceuticals within 12 weeks before the start of study intervention
• Previous participation in other clinical studies within 28 days before the start of study treatment or 5 half-lives of the investigational treatment of the previous study, whichever is longer Diagnostic assessments

Sponsors & Collaborators

• Bayer: lead

Study Sites (7)

Oregon Health and Science University

Portland, Maine, 97239, United States

Location

New Jersey Urology, LLC

Voorhees Township, New Jersey, 08043, United States

Location

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MidLantic Urology - Bala Cynwyd

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Bon Secours St. Francis Hospital

Greenville, South Carolina, 29607, United States

Location

Carolina Urological Research Center

Myrtle Beach, South Carolina, 29579, United States

Location

MeSH Terms

Conditions

Prostatic Neoplasms, Castration-Resistant

Interventions

darolutamide; enzalutamide

Condition Hierarchy (Ancestors)

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Limitations and Caveats

A total of 30 participants received treatment with darolutamide 600 mg twice daily in the lead in phase of the study, comprising the safety evaluable population. No participant received either darolutamide or enzalutamide in the randomized phase of the study as the study was terminated prematurely prior to the initiation of the randomized phase of the study.

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: Bayer

clinical-trials-contact@bayer.com

(+) 1-888-8422937

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 21, 2019
• First Posted: November 8, 2019
• Study Start: December 17, 2019
• Primary Completion: July 8, 2022
• Study Completion: July 8, 2022
• Last Updated: August 4, 2023
• Results First Posted: August 4, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)