Cancer of the Prostate, Hormone Sensitive Prostate Cancer, Metastatic Castration Sensitive Prostate Cancer (mCSPC), Prostate Cancer
Conditions
Keywords
Hormone Sensitive Prostate Cancer, Mevrometostat, Metastatic castration sensitive prostate cancer, PF-06821497, EZH2, enhancer of zeste homologue-2, enzalutamide, mCSPC, HSPC, Prostate cancer, castrate sensitive prostate cancer, prostatecancer-study.com, Phase 3, efficacy, safety, pharmacokinetics, pharmacodynamics
Brief summary
This study will explore whether a combination of the investigational drug mevrometostat (PF-06821497) and enzalutamide will work better than taking enzalutamide alone in participants with mCSPC who are ARPI naïve and have not yet received chemotherapy in the mCSPC setting.
Detailed description
This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating mevrometostat in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCSPC who have not received systemic anticancer treatments with the exception of androgen-deprivation therapy (ADT) and first-generation antiandrogen agents. Prior therapy with up to 3 months of ADT (chemical or surgical) is allowed, with no radiographic evidence of disease progression or rising PSA levels prior to Day 1. This study consists of a Screening Phase, Randomization, Treatment Phase, Safety Follow-up, and Long-Term Follow-up. Participants will be randomized on a 1:1 basis to receive (Arm A) mevrometostat (PF-06821497) in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.
Interventions
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study. Participants will receive mevrometostat or matching placebo in a blinded fashion. Participants, investigators and site staff, and sponsor staff will be aware that participants in both study arms are receiving enzalutamide. Enzalutamide will be provided in an open-label manner to participants in each treatment arm. Participants and their caregivers will be blinded to their assigned study intervention. Investigators and other site staff will be blinded to participants' assigned study intervention Sponsor staff will be blinded to participants' assigned study intervention, except for sponsor staff involved in the assignment or distribution of study intervention.
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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 prostate cancer documented by positive bone scan (for bone disease) or metastatic lesion(s) on CT or MRI (for soft tissue/visceral disease). * Resolution of acute effects of any prior therapy to either baseline severity or CTCAE Grade ≤1 (except for AEs which do not constitute a safety risk in the investigator's judgement). * Participants must have ECOG PS 0 or 1.
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. * Clinically significant cardiovascular disease. * Known or suspected brain metastasis or active leptomeningeal disease. * Participants must be treatment naïve at the mCSPC stage, eg, participants cannot have received any cytotoxic chemotherapy with the following exceptions: Treatment with first-generation antiandrogen (ADT) agents is allowed for mCSPC. * Previous administration with an investigational product (drug or vaccine) within 30 days. * Use of 5-alpha reductase inhibitors is prohibited within 28 days of randomization. * Prior surgery from which the participant has not fully recovered at least 28 days prior to randomization * 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). * Inadequate organ function. * Known allergic or hypersensitivity reactions to mevrometostat or its excipients or to enzalutamide or its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression Free Survival (rPFS) | Randomization up to approximately 4 years | rPFS is defined as the time from randomization until PD based on BICR assessment per RECIST v1.1 (soft tissue disease) and PCWG3 (bone disease), or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | Randomization up to approximately 9 years | OS defined as the time from the date of randomization until the date of death due to any cause. |
| Objective response in measurable soft tissue disease | Randomization up to approximately 4 years | The proportion of participants with measurable soft tissue disease at baseline who have a confirmed objective response of CR or PR per RECIST v1.1 will be summarized along with the 95% CI. |
| Duration of Response (DoR) in measurable soft tissue disease | Randomization up to approximately 4 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. |
| Prostate Specific Antigen Response | Randomization up to approximately 4 years | The proportion of participants with a 50% decline from baseline in PSA that is confirmed by a second consecutive value at least 21 days later in participants with detectable PSA values at baseline will be calculated for each treatment arm. |
| Time to prostate specific antigen (PSA) progression | Randomization up to approximately 4 years | Time from the date of randomization to the date of the first PSA progression. |
| Time to initiation of antineoplastic therapy | Randomization up to approximately 4 years | Time from randomization to first use of new antineoplastic therapy for prostate cancer. |
| Time to first symptomatic skeletal event | Randomization up to approximately 4 years | Time from randomization to first tumor-related symptomatic bone fracture, surgery or radiotherapy to the bone, and spinal cord compression, whichever occurs first. |
| Time from randomization to CRPC | Randomization up to approximately 4 years | Time from randomization to the first date of CRPC event. |
| Incidence of Adverse Events | 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 evaluate the PK of mevrometostat when dosed in combination with enzalutamide | Cycle 3 Day 1 to last PK draw at Cycle 5 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) | 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. |
| Change from baseline in health-related quality of life (HRQoL) per Functional Assessment of Cancer Therapy - Prostate (FACT-P) | 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. |
| Time to definitive deterioration in patient-reported health related quality of life (HRQoL) per FACT-P | 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 |
| Patient-reported outcomes in cancer specific symptoms - time to definitive deterioration | Randomization up to approximately 5 years | Change from baseline and time to definitive deterioration in participant-reported prostate cancer specific functioning, and symptoms per EORTC QLQ-PR25 |
| Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms per BFI | Randomization up to approximately 5 years | Change from baseline and time to confirmed deterioration in participant-reported fatigue symptoms (fatigue severity and fatigue interference) as per BFI. |
| Change from baseline in participant-reported general health status per EQ-5D-5L | 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. |
| To assess circulating tumor DNA (ctDNA) at baseline and on treatment to evaluate tumor burden | Baseline up to approximately 4 years | Evaluation of ctDNA burden at baseline and on study. |
| Prostate Specific Antigen Response, Undetectable PSA after Randomization | Randomization up to approximately 4 years | The proportion of participants with undetectable PSA values after randomization, in participants with detectable PSA values at baseline, will be calculated for each treatment arm. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, China, Czechia, Finland, France, Germany, Greece, Israel, Italy, Japan, Netherlands, New Zealand, Poland, Slovakia, South Korea, Spain, Switzerland, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed