Clinical trial NCT04157088: 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)
Official title: A Randomized, Open-label, Multicenter, Phase 2b Study to Evaluate Physical Function, Including Balance and Daily Activity, in Participants With Castration-resistant Prostate Cancer Treated With Darolutamide or Enzalutamide
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Prostatic Cancer, Castration-Resistant
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2019-11-08
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
  * For mCRPC participants: any chemotherapy, and/or \>2 prior lines of systemic anticancer treatment. Treatment with an LHRH agonist, LHRH antagonists, or orchidectomy is not counted as systemic treatment with regard to this exclusion criterion.
* 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

Primary outcomes:
measure: Number of Participants With a Worsening in TUG Time During the 24- Week Period.
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Number of Participants With an Increase of at Least 1 Second in TUG Time at 12 and 24 Weeks and During the 52 Weeks.
timeFrame: At 12 week, 24 week and 52 week.
measure: Time to Worsening (Increase of at Least 1 Second) in TUG Time
timeFrame: From randomization to the first date a participant had a worsening.
measure: 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.
timeFrame: At 12 and 24 weeks and during the 24 weeks and 52 weeks from baseline
measure: 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.
timeFrame: At 12 week, 24 week and 52 week
measure: 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.
timeFrame: At 12, 24, and 52 weeks for the randomization phase
measure: Number of Participants With a Decline in Cognitive Function During the 24 Weeks and 52 Weeks From Baseline, as Assessed by HVLT-R.
timeFrame: During the 24 weeks and 52 weeks from baseline.
measure: Number of Participants With a Decline in Cognitive Function During the 24 Weeks and 52 Weeks From Baseline, as Assessed by TMT.
timeFrame: During the 24 weeks and 52 weeks from baseline.
measure: Number of Participants With a Decline in Cognitive Function During the 24 Weeks and 52 Weeks From Baseline, as Assessed by COWA.
timeFrame: During the 24 weeks and 52 weeks from baseline.
measure: Number of Participants With a Decline Using a Selected Domain of Functional Assessment of Cancer Therapy-Cognitive (FACT-Cog).
timeFrame: During the 24 weeks and 52 weeks from baseline.
measure: Number of Participants With a Worsening of Fatigue During the 24 Weeks and 52 Weeks.
timeFrame: Up to 52 weeks in randomization phase.
measure: Number of Participants With an Increase of at Least 1 Point in Fatigue Interference by 24 Weeks and 52 Weeks From Baseline (Based on Items 4A-F of the BFI)
timeFrame: At 24 weeks and 52 weeks
measure: Number of Participants With a Worsening in Scores in the PHQ-9 During the 24 Weeks and 52 Weeks From Baseline.
timeFrame: Up to 52 weeks in randomization phase
measure: Number of Participants With Treatment Emergent AEs, SAEs, and AEs Leading to Study Intervention Discontinuation
timeFrame: Up to 52 weeks
measure: Number of Participants With AEs of Interest, Including Falls, Fractures, and Hypothyroidism
timeFrame: Up to 52 weeks
measure: Time to Deterioration of Karnofsky Performance Scale (KPS) Defined as at Least a 10 Point Decline From Baseline.
timeFrame: From randomization to the first date the participant had had a decline in KPS of at least 10 points.
measure: Number of Participants With Treatment Exposure of the Study Intervention Including Time on Treatment
timeFrame: Up to 52 weeks
measure: Number of Participants With Dose Reductions of Study Intervention
timeFrame: Up to 52 weeks in randomization phase
measure: Time to Prostate-specific Antigen (PSA) Progression (as Per Prostate Cancer Working Group [PCWG3] Criteria)
timeFrame: From randomization to the time when the criteria for PSA progression (according to PCWG3) was met, up to 52 weeks.
measure: Survival Status
timeFrame: Up to 52 weeks in randomization phase
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health and Science University
state: Maine
city: Voorhees
country: United States
facility: New Jersey Urology, LLC
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Bala-Cynwyd
country: United States
facility: MidLantic Urology - Bala Cynwyd
state: Pennsylvania
city: Greenville
country: United States
facility: Bon Secours St. Francis Hospital
state: South Carolina
city: Myrtle Beach
country: United States
facility: Carolina Urological Research Center
state: South Carolina
Study officials:
References: