A Study to Learn About the Investigational Medicine Called PF-06821497 (Mevrometostat) in Men With mCRPC Who Were Previously Treated With Abiraterone Acetate for Prostate Cancer (MEVPRO-1).

JRCT ID: jRCT2051240128

Registered date:18/09/2024

Basic Information

• Recruitment status: Pending
• Health condition(s) or Problem(s) studied: *Metastatic Castrate Resistant Prostate Cancer (mCRPC)
• Date of first enrollment: 23/04/2023
• Target sample size: 600
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

*Drug: PF-06821497
-875 mg BID (2 times a day)
-Other Names:
#EZH2i

*Drug: Docetaxel
-75 mg/m2 IV (every 21 days)
-Other Names:
#Taxotere

*Drug: Enzalutamide
-160 mg QD
-Other Names:
#XTANDI

Outcome(s)

Primary Outcome

*Radiographic Progression Free Survival (rPFS) assessed by blinded independent central review (BICR) per RECIST v1.1 and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) [Time Frame: Randomization up to approximately 2 years.]
-rPFS is defined as the time from the date of randomization to first objective evidence of radiographic progression as assessed in soft tissue per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or in bone per Prostate Cancer Clinical Trials Working Group 3 (PCWG3) guidelines by BICR, or death, whichever occurs first.

Secondary Outcome

*Overall survival(OS) [Time Frame:Randomization up to approximately 4.5 years]
-OS is defined as the time from the date of randomization to the date of death due to any cause
*Objective Response(ORR) [Time Frame:Randomization up to approximately 4.5 years]
-The objective response rate is defined as the proportion of participants with measurable soft tissue disease at baseline who have a confirmed objective response of complete response (CR) or partial response (PR) per RECIST v1.1.
*Duration of Response(DoR) in measurable soft tissue disease [Time Frame:Randomization up to approximately 4.5 years]
-The DoR is defined as the first objective evidence of soft tissue response (CR or PR, whichever is earlier) to radiographic progression or death due to any cause whichever occurs first
*Time to prostate specific antigen(PSA) progression. [Time Frame:Randomization up to approximately 4.5 years]
-Proportion of participants with PSA response >=50% in participants with detectable PSA values at baseline
*Time to initiation of antineoplastic therapy. [Time Frame:Randomization up to approximately 4.5 years]
-Time from randomization to first use of new antineoplastic therapy
*Prostate Specific Antigen Response [Time Frame:Randomization up to approximately 4.5 years]
-Proportion of participants with PSA response >=50% in participants with detectable PSA values at baseline
*Incidence of Adverse Events [Time Frame:Randomization up to approximately 4.5 years]
-Type, incidence, severity [as graded by National Cancer Institute(NCI) common terminology criteria for adverse events(CTCAE) v5.0], seriousness and relationship to study medications of AEs
*Time to first symptomatic skeletal event [Time Frame:Randomization up to approximately 4.5 years]
-Time from randomization to first symptomatic skeletal event(symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first)
*Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form(BPI-SF) [Time Frame:Randomization up to approximately 4.5 years]
-Analysis of Brief Pain Inventory-Short Form(BPI-SF) will be based on the pain severity score(mean of individual BPI-SF items 3, 4, 5 and 6), the pain interference score (mean of items 9A-9G), and the single BPI-SF Item 3 which asks the patient to rate pain at its worst in the last 24 hours
*Change from baseline in health-related quality of life(HRQoL) per Functional Assessment of Cancer Therapy - Prostate(FACT-P) [Time Frame:Randomization to approximately 4.5 years]
-Change from baseline in HRQoL(FACT-P total score) will be presented. The FACT-P total score will be calculated based on the participant responses to the 39 items in the FACT-P questionnaire. Each item is rated on a 0 to 4 Likert-type scale and then combined to produce the FACT-P total score(0-156), with higher scores representing better health-related quality of life
*Change from baseline in social/family well-being per Functional Assessment of Cancer Therapy - Prostate(FACT-P) [Time Frame:Randomization up to approximately 4.5 years]
-Change from baseline in social/family well-being score will be presented. The social/family well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale
*Change from baseline in emotional well-being per FACT-P [Time Frame:Randomization up to approximately 4.5 years]
-Change from baseline in emotional well-being score will be presented. The emotional well-being score will be calculated based on 6 items in the FACT-P questionnaire; score range 0-24. Each item is rated on a 0 to 4 Likert-type scale
*Change from baseline in functioning well-being per FACT-P [Time Frame:Randomization up to approximately 4.5 years]
-Change from baseline in functioning well-being score will be presented. The functioning well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale
*Change from baseline in physical well-being per FACT-P[Time Frame:Randomization to approximately 4.5 years]
-Change from baseline in physical well-being score will be presented. The physical well-being score will be calculated based on 7 items in the FACT-P questionnaire; score range 0-28. Each item is rated on a 0 to 4 Likert-type scale
*Change from baseline in symptoms per FACT-P [Time Frame:Randomization up to approximately 4.5 years]
-Change from baseline prostate cancer symptoms (PCS) score will be presented. The PCS score will be calculated based on 12 items in the FACT-P questionnaire; score range 0-48. Each item is rated on a 0 to 4 Likert-type scale
*Change from baseline in patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L) [Time Frame:Randomizaton up to approximately 4.5 years]
-Participants will self-rate their current state of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression by choosing 1 of 5 possible responses that record the level of severity (no problems, slight problems, moderate problems, severe problems, or extreme problems) within each dimension. The questionnaire also includes a visual analog scale to self-rate general health state on a scale from "the worst health you can imagine" to "the best health you can imagine."
*Symptomatic toxicity as measured by items from the Patient-Reported Outcome CTCAE (PRO-CTCAE) [Time Frame:Randomization up to approximately 4.5 years]
-Each selected PRO-CTCAE items will be assessed related to one or more attributes that include counts for the frequency, severity, and/or interference with usual or daily activities
*Overall side effect burden as measured by the FACT- GP5 [Time Frame:Randomization to approximately 4.5 years]
-The FACT-GP5 question assesses overall side effect burden with the following response options "I am bothered by side effects of treatment," is rated on a 5-point scale ranging from "not at all" (0) to "very much" (4) and counts will be presented
*Time to confirmatory deterioration in patient-reported pain symptoms per BPI-SF Item 3 "worst pain in 24 hours" [Time Frame:Randomization up to approximately 4.5 years]
-Defined as the time from randomization to onset of pain progression, which is defined as > 2-point increase from baseline in the score from the BPI-SF Question 3 that is confirmed at the next consecutive assessment > 4 weeks apart or an initial deterioration followed by death before the next assessment
*Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P [Time Frame:Randomization up to approximately 4.5 years]
-Defined as the time from randomization to onset of definitive deterioration in FACT-P total score, which is defined as >10 point decrease from baseline and no subsequent observations with a <10 point decrease from baseline FACT-P total score
*Time to definitive deterioration in patient-reported physical well-being per FACT-P [Time Frame:Randomization up to approximately 4.5 years]
-Time to definitive deterioration in physical well-being (PWB) per FACT-P is defined as the time from randomization to onset of definitive deterioration in physical well-being, which is defined as >=3-point
*To evaluate the PK of PF-06821497 when dosed with enzalutamide [Time Frame:Cycle 1(each cycle is 28 days), Day 1 to last PK draw at the end of Cycle 6, Day 1]
-PK characterized by pre-dose trough and post-dose plasma concentrations of PF-06821497 at selected visits
*To assess circulating tumor DNA(ctDNA) at baseline and on treatment to evaluate tumor burden. [Time Frame:Baseline up to approximately 2 years]
-Evaluation of ctDNA burden at baseline and on study

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Male

Include criteria

Inclusion Criteria:
*Histologically or cytologically confirmed adenocarcinoma of the prostate without small cell features.
*Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
*Surgically or medically castrated, with serum testosterone <=50 ng/dL (<=1.73 nmol/L) at screening.
*Progressive disease in the setting of surgical or medical castration. Note: Evidence of disease progression with at least 12 weeks of abiraterone acetate in the metastatic castrate sensitive prostate cancer (mCSPC) setting, or first line metastatic castrate resistant prostate cancer (mCRPC) setting is required.
*Eastern Cooperate Oncology Group (ECOG) performance status 0 - 2, with life expectancy of at least 6 months as assessed by the investigator.

Exclude criteria

Exclusion Criteria:
*Any medical (including active or clinically significant bacterial, fungal or viral infection) or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may increase the risk of study participation or, in the investigator's judgment, make the participant inappropriate for the study.
*Clinically significant cardiovascular disease.
*Central nervous system (CNS) pathology/neurological findings including known or suspected brain metastasis or active leptomeningeal disease, symptomatic or impending spinal cord compression or cauda equina syndrome, or clinically significant history of seizure or any condition that may predispose to seizure.
*Prior treatment for prostate cancer at any stage with any cytotoxic chemotherapy, radioligand therapy, androgen receptor signaling inhibitors (ARSi) including enzalutamide, apalutamide, darolutamide, poly ADP-ribose polymerase (PARP) monotherapy or other systemic anti-cancer treatment (approved drugs or experimental compounds such as, antibody therapy, immunotherapy, gene therapy, angiogenesis inhibitors, EZH2 inhibitors).
*Inadequate renal function defined by an estimated glomerular filtration rate (eGFR) <45 mL/min.
*Hepatic dysfunction.
*Hematologic abnormalities

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT06551324