Metastatic Castrate Resistant Prostate Cancer (mCRPC)
Conditions
Keywords
Prostate cancer, Enhancer of zeste homolog 2, castrate resistant prostate cancer, Hormone resistant, Metastatic hormone resistant prostate cancer, Metastatic castrate resistant prostate cancer, PF-06821497, Enzalutamide, Docetaxel, Advanced prostate cancer, Efficacy, Safety, Open-label, Relapsed, refractory
Brief summary
Pfizer MEVPRO-1 (C2321014) is a randomized, open-label, multi-center clinical trial evaluating whether combining the study medicine (PF-06821497) with enzalutamide is safe and effective compared to physician's choice of either second-line androgen receptor (AR) directed therapy with enzalutamide or docetaxel (chemotherapy) for treating metastatic castration-resistant prostate cancer (mCRPC) after progression on prior abiraterone acetate treatment. The primary objective of this clinical trial is to assess the radiographic progression free survival (rPFS) of the combination of PF-06821497 plus enzalutamide versus physician's choice of enzalutamide or docetaxel.
Interventions
DRUGPF-06821497
875 mg BID (2 times a day)
DRUGDocetaxel
75 mg/m2 IV (every 21 days)
DRUGEnzalutamide
160 mg QD
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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. * Progressive disease in the setting of surgical or medical castration with evidence of disease progression on treatment with abiraterone acetate in the mCSPC setting or first line 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.
Exclusion criteria
* Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that may make the participant inappropriate for the study. * Know 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 or clinically significant history of seizure. * Prior treatment for prostate cancer at any stage with any cytotoxic chemotherapy, radioligand therapy (i.e. 177Lu-PSMA-617, radium 223), androgen receptor signaling inhibitors (ARSi) including enzalutamide, apalutamide, darolutamide, poly ADP-ribose polymerase (PARP) monotherapy or other systemic anti-cancer treatment, with the following exceptions: 1. Treatment with first-generation antiandrogen agents, if discontinued prior to first dose of study intervention. 2. Docetaxel treatment is allowed for mCSPC, as long as no signs of failure, or disease progression occurred during treatment or within 3 months of treatment completion. * Previous administration with an investigational product within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is shorter). * Inadequate organ function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) | 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
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 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) | Randomization up to approximately 2 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 | Randomization up to approximately 2 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. | Randomization up to approximately 2 years. | Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline. |
| Time to initiation of antineoplastic therapy. | Randomization up to approximately 4.5 years. | Time from randomization to first use of new antineoplastic therapy. |
| Prostate Specific Antigen Response | Randomization up to approximately 2 years. | Proportion of participants with PSA response ≥50% in participants with detectable PSA values at baseline. |
| Incidence of Adverse Events | 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 | Randomization up to approximately 2 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) | 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) | 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) | 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 Functional Assessment of Cancer Therapy - Prostate (FACT-P) | 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 Functional Assessment of Cancer Therapy - Prostate (FACT-P) | 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 Functional Assessment of Cancer Therapy - Prostate (FACT-P) | 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 Functional Assessment of Cancer Therapy - Prostate (FACT-P) | 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) | 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) | 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 | 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" | 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 | 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 | 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 | 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. | Baseline up to approximately 2 years. | Evaluation of ctDNA burden at baseline and on study. |
Countries
Argentina, Australia, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, Italy, Japan, Netherlands, Poland, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTPfizer CT.gov Call Center
STUDY_DIRECTORPfizer CT.gov Call Center
Pfizer
Outcome results
None listed