A Phase 3, Randomized, Double Blind, Placebo Controlled Study of Pf-06821497 (Mevrometostat) With Enzalutamide in Metastatic Castration Resistant Prostate Cancer (Mevpro-2)
A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.
Kawai Norisuke
Pfizer R&D Japan G.K.
Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo
+81-3-5309-7000
clinical-trials@pfizer.com
Clinical Trials Information Desk
Pfizer R&D Japan G.K.
Shinjuku Bunka Quint Bldg., 3-22-7 Yoyogi, Shibuya-ku, Tokyo
+81-3-5309-7000
clinical-trials@pfizer.com
Recruiting
Oct. 30, 2024
Oct. 30, 2024
900
Interventional
randomized controlled trial
double blind
active control
parallel assignment
treatment purpose
Inclusion Criteria:
*Male participants aged >=18 years (or the minimum age of consent in accordance with local regulations) at screening.
*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.
*Metastatic disease in bone documented on bone scan, or in soft tissue documented on CT/MRI scan.
*Progressive disease in the setting of medical or surgical castration.
*Prior to randomization, there must be resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade <=1.
*ECOG performance status 0 or 1, with a life expectancy of >=12 months as assessed by the investigator.
Exclusion Criteria:
*Any medical 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.
*Known history of active inflammatory gastrointestinal disease, chronic diarrhea, or previous gastric resection or lap-band surgery.
*Clinically significant cardiovascular disease.
*Known or suspected brain metastasis or active leptomeningeal disease.
*Participants must be treatment naive at the mCRPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents and. Docetaxel treatment is allowed for mCSPC.
*Previous administration with an investigational product (drug or vaccine) within 30 days.
*Current use or anticipated need for drugs that are known strong CYP3A4/5 inhibitors and inducers (with exception of enzalutamide as part of this study).
*Major surgery or palliative localized radiation therapy within 14 days before randomization.
*Inadequate organ function.
*Radiographic Progression Free Survival (rPFS) [Time Frame: Randomization up to approximately 3 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.
*Overall survival (OS) [Time Frame: Randomization up to approximately 5 years]
-OS is defined as the time from the date of randomization to the date of death due to any cause.
*To demonstrate that PF-06821497 in combination with enzalutamide is superior to placebo in combination with enzalutamide in prolonging TTPP [Time Frame: Randomization up to approximately 3 years]
-TTPP (alpha protected): assessed using time to first >=2-point increase from baseline score on BPI-SF Item 3 (Worst Pain) observed at 2 consecutive visits or the initiation of short- or long-acting opioid use for pain
*Duration of Response (DoR) in measurable soft tissue disease [Time Frame: Randomization up to approximately 3 years.]
-The DoR is defined as the time from 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 3 years]
-Time from the date of randomization to the date of the first PSA progression. PSA progression is defined as a >=25% increase in PSA with an absolute increase of >=2 ng/mL above the nadir (or baseline for participants with no PSA decline), confirmed by a second consecutive PSA value at least 21 days later.
*Prostate Specific Antigen Response [Time Frame: Randomization up to approximately 3 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 3 years.]
-Time from randomization to first use of new antineoplastic therapy.
*Time to initiation of cytotoxic chemotherapy. [Time Frame: Randomization up to approximately 3 years]
-Time from randomization to first use of new cytotoxic chemotherapy.
*Time to first symptomatic skeletal event [Time Frame: Randomization up to approximately 3 years.]
-Time from randomization to first symptomatic skeletal event (symptomatic bone fractures, spinal cord compression, surgery or radiation to the bone whichever is first).
*Progression free survival on next line of therapy [Time Frame: Randomization up to approximately 3 years]
-the time from the date of randomization to the first occurrence of investigator-determined disease progression (PSA progression, progression on imaging, or clinical progression) or death due to any cause, whichever occurs first, while the participant was receiving first subsequent therapy for prostate cancer.
*Incidence of Adverse Events [Time Frame: Randomization up to approximately 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.
*To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden. [Time Frame: Baseline up to approximately 3 years.]
-Evaluation of ctDNA burden at baseline and on study.
*To evaluate the PK of PF-06821497 when dosed with enzalutamide [Time Frame: Cycle 1 Day 15 to last PK draw at Cycle 6 Day 1 (cycle length is 28 days)]
-PK characterized by pre-dose trough and post-dose plasma concentrations of PF-06821497 at selected visits
*Change from baseline in patient reported pain symptoms per Brief Pain Inventory-Short Form (BPI-SF) [Time Frame: Randomization up to approximately 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 BPI-SF Item 3 (Worst Pain) at Cycle 7 Day 1 (Week 25) [Time Frame: Randomization up to Week 25]
-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 up to approximately 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 patient reported health status per European Quality of Life 5-Dimension 5 Level (EQ-5D-5L) [Time Frame: Randomization up to approximately 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 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.
*Time to definitive deterioration in patient-reported HRQoL per FACT-P [Time Frame: Randomization up to approximately 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
Pfizer Japan Inc.
Hokkaido University Hospital Institutional Review Board
Kita 14, Nishi 5, Kita-ku, Sapporo, Hokkaido
+81-11-706-7061
tiken@med.hokudai.ac.jp
Approval
Aug. 20, 2024
Yes
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
NCT06629779
ClinicalTrials.gov
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