The purpose of this study is to assess the efficacy and safety of opevesostat plus daily corticosteroids compared to alternative abiraterone acetate or enzalutamide in participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) previously treated with one next-generation hormonal agent (NHA). The primary study hypothesis is that opevesostat is superior to alternative abiraterone acetate or enzalutamide with respect to overall survival (OS), in androgen receptor ligand binding domain (AR LBD) mutation positive and negative participants.
Per Protocol Amendment 08, OS was moved to be a secondary outcome measure. Per Protocol Amendment 11, OS was returned to a primary outcome measure.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,314
Administered orally
Administered orally
Administered orally
Administered orally or IM as a rescue drug
Administered orally
Administered orally
Administered orally
The University of Arizona Cancer Center - North Campus ( Site 0073)
Tucson, Arizona, United States
RECRUITINGCHAO Family Comprehensive Cancer Center and Ambulatory Care ( Site 0120)
Irvine, California, United States
RECRUITINGUCLA Hematology/Oncology - Santa Monica ( Site 0044)
Los Angeles, California, United States
RECRUITINGUniversity of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0040)
Orange, California, United States
Overall Survival (OS)
OS is defined as the time from randomization to death due to any cause.
Time frame: Up to approximately 82 months
Radiographic Progression-Free Survival (rPFS)
rPFS is defined as the time from randomization to the first documented disease progression per PCWG-modified RECIST 1.1 by BICR or death due to any cause, whichever occurs first.
Time frame: Up to approximately 52 months
Time to Initiation of the First Subsequent Anticancer Therapy (TFST)
TFST is defined as the time from randomization to initiation of the first subsequent anti-cancer therapy or death, whichever occurred first.
Time frame: Up to approximately 82 months
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per PCWG-modified RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
Time frame: Up to approximately 82 months
Duration of Response (DOR)
For participants who demonstrate confirmed CR or PR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression per PCWG-modified RECIST 1.1 as assessed by BICR or death from any cause, whichever occurs first.
Time frame: Up to approximately 82 months
Time to Pain Progression (TTPP)
TTPP is defined as the time from randomization to pain progression. TTTP is assessed by Brief Pain Inventory-Short Form (BPI-SF) Item 3 ("Worst Pain in 24 Hours") and opiate analgesic use (Analgesic Quantification Algorithm \[AQA\] Score).
Time frame: Up to approximately 82 months
Change From Baseline in Functional Assessment of Cancer Therapy-General (FACT-G) Total Score
The FACT-G is a health-related quality of life (HRQoL) 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. The change from baseline in FACT-G total score will be reported.
Time frame: Baseline and up to approximately 82 months
Time to Deterioration (TTD) in FACT-G Total Score
The FACT-G is a HRQoL 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. TTD in FACT-G total score will be reported.
Time frame: Up to approximately 82 months
Overall Improvement in FACT-G Total Score
The FACT-G is a HRQoL 27-item questionnaire in participants being treated for cancer. The FACT-G subscales include Physical Well-Being (PWB), Social/Family Well-Being (SWB), Emotional Well-Being (EWB), and Functional Well-Being (FWB). All items are scored on a 5-point Likert scale of 0 (not at all) to 4 (very much). The total score can range from 0 to 108. Higher scores indicate higher HRQoL. The overall improvement in FACT-G total score will be reported.
Time frame: Up to approximately 82 months
Time to Prostate-specific Antigen (PSA) Progression
The time to PSA progression is the time from randomization to PSA progression. The PSA progression date is defined as the date of: 1) ≥25% increase and ≥2 ng/mL above the nadir, confirmed by a second value ≥3 weeks later if there was PSA decline from baseline; OR 2) ≥25% increase and ≥2 ng/mL increase from baseline.
Time frame: Up to approximately 82 months
PSA Response Rate
The PSA response rate is the percentage of participants who had PSA response defined as a reduction in the PSA level from baseline by ≥50%. The reduction in PSA level was confirmed by an additional PSA evaluation performed ≥3 weeks from the original response.
Time frame: Up to approximately 82 months
Time to First Symptomatic Skeletal-Related Event (TSSRE)
TSSRE is the time from randomization to the first symptomatic skeletal-related event defined as: 1. use of external-beam radiation therapy (EBRT) to prevent or relieve skeletal symptoms 2. occurrence of new symptomatic pathologic bone fracture (vertebral or non-vertebral) 3. occurrence of spinal cord compression 4. tumor-related orthopedic surgical intervention, whichever occurs first.
Time frame: Up to approximately 82 months
Number of Participants Who Experience an AE
An AE is defined as any unfavorable and unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience one or more AE will be reported.
Time frame: Up to approximately 82 months
Number of Participants Who Discontinue Study Treatment Due to an AE
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study treatment due to an AE will be reported.
Time frame: Up to approximately 82 months
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Stanford Cancer Center ( Site 0036)
Palo Alto, California, United States
RECRUITINGEmad Ibrahim,MD,INC. ( Site 0012)
Redlands, California, United States
COMPLETEDKaiser Permanente Riverside Medical Center ( Site 0099)
Riverside, California, United States
RECRUITINGUniversity of California Davis (UC Davis) Comprehensive Cancer Center ( Site 0114)
Sacramento, California, United States
RECRUITINGSan Francisco VA Health Care System ( Site 0093)
San Francisco, California, United States
RECRUITINGKaiser Permanente-Kaiser Permanente, Vallejo Medical Center, Adult Oncology ( Site 0101)
Vallejo, California, United States
ACTIVE_NOT_RECRUITING...and 320 more locations