A Study to Learn How PF-06821497 (Mevrometostat) Works in Men With Metastatic Castration-resistant Prostate Cancer.
- Conditions
- Metastatic Castration-Resistant Prostate Cancer
- Interventions
- Registration Number
- NCT06629779
- Lead Sponsor
- Pfizer
- Brief Summary
This study will explore whether a combination of the investigational drug PF-06821497 and enzalutamide will work better than taking enzalutamide alone in participants with mCRPC who are ARSi or abiraterone naïve.
- Detailed Description
This is a global, multicenter, randomized Phase 3 study evaluating PF-06821497 (mevrometostat) in combination with enzalutamide versus placebo in combination with enzalutamide in participants with mCRPC where no systemic anti-cancer treatments have been initiated after documentation of mCRPC with the exception of ADT (androgen deprivation therapy) and first-generation anti-androgen agents. Prior treatment with any of the ARSi's enzalutamide, darolutamide, apalutamide, or abiraterone acetate, is not permitted in any setting. Chemotherapy is permitted in the castrate sensitive setting.
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) PF-06821497 in combination with enzalutamide, or (Arm B) placebo in combination with enzalutamide.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- Male
- Target Recruitment
- 900
- 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 medical or surgical castration.
- ECOG performance status 0 or 1, with a life expectancy of ≥12 months as assessed by the investigator.
-
Any medical or psychiatric condition including recent (within the past year) or active suicidal ideation/behavior or laboratory abnormality that 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 or clinically significant history of seizure.
-
Any history of myelodysplastic syndrome, acute myeloid leukemia, or any other prior malignancy with a few exceptions.
-
Participants must be treatment naïve at the mCRPC stage, eg, no cytotoxic chemotherapy, radio-ligand therapy (i.e. 177Lu- PSMA-617), CDK4/6 inhibitors, 5-alpha reductase inhibitors for prostate cancer in any setting, 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:
- Treatment with first-generation antiandrogen (ADT) agents;
- 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 (drug or vaccine) within 30 days or 5 half-lives preceding the first dose of study intervention (whichever is longer).
-
Inadequate organ function.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A PF-06821497 Participants will receive PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily) Arm A Enzalutamide Participants will receive PF-06821497 (875 mg) BID (twice daily) + enzalutamide 160 mg QD (once daily) Arm B Placebo Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily) Arm B Enzalutamide Participants will receive Placebo BID (twice daily) + enzalutamide 160 mg QD (once daily)
- Primary Outcome Measures
Name Time Method Radiographic Progression Free Survival (rPFS) 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.
- Secondary Outcome Measures
Name Time Method Overall survival (OS) 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 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 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. 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 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. Randomization up to approximately 3 years. Time from randomization to first use of new antineoplastic therapy.
Time to initiation of cytotoxic chemotherapy. Randomization up to approximately 3 years Time from randomization to first use of new cytotoxic chemotherapy.
Time to first symptomatic skeletal event 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 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 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. 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 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) 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) 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) 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) 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) 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 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
Trial Locations
- Locations (160)
NextStage Clinical Research-Chicago-(04)
🇺🇸Lisle, Illinois, United States
Ironwood Cancer & Research Centers
🇺🇸Scottsdale, Arizona, United States
Palo Verde Hematology Oncology
🇺🇸Glendale, Arizona, United States
Arizona Urology Specialists (East Side Location)
🇺🇸Tucson, Arizona, United States
Arizona Urology Specialists (AUS)-Orange Grove
🇺🇸Tucson, Arizona, United States
Highlands Oncology
🇺🇸Rogers, Arkansas, United States
Highlands Oncology Group
🇺🇸Springdale, Arkansas, United States
Adventist Health Physicians Network
🇺🇸Napa, California, United States
Adventist Health St. Helena
🇺🇸Saint Helena, California, United States
Duly Health and Care (Bone Scintigraphy)
🇺🇸Lisle, Illinois, United States
Blessing Hospital
🇺🇸Quincy, Illinois, United States
Blessing Physician Services
🇺🇸Quincy, Illinois, United States
Duly Health and Care (CT and MRI)
🇺🇸Westmont, Illinois, United States
Adult & Pediatric Urology, PC
🇺🇸Omaha, Nebraska, United States
Montefiore Medical Center - Medical Park
🇺🇸Bronx, New York, United States
Salisbury VA Medical Center
🇺🇸Salisbury, North Carolina, United States
AUC Urologists, LLC
🇺🇸Myrtle Beach, South Carolina, United States
Carolina Urologic Research Center, LLC
🇺🇸Myrtle Beach, South Carolina, United States
Grand Strand Medical Center
🇺🇸Myrtle Beach, South Carolina, United States
Parkway Surgery Center
🇺🇸Myrtle Beach, South Carolina, United States
USA Clinical Trials
🇺🇸San Antonio, Texas, United States
Harborview Medical Center
🇺🇸Seattle, Washington, United States
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
University of Washington Medical Center - Montlake
🇺🇸Seattle, Washington, United States
Centro de Urología (CDU)
🇦🇷Caba, Buenos Aires, Argentina
Hospital Sirio Libanes
🇦🇷Capital Federal, Buenos Aires, Argentina
Imagenes Mdq
🇦🇷Mar del Plata, Buenos Aires, Argentina
Instituto de Investigaciones Clínicas Mar del Plata
🇦🇷Mar del Plata, Buenos Aires, Argentina
Centro Medico Privado CEMAIC
🇦🇷Capital, Córdoba, Argentina
Hospital Privado Universitario de Córdoba
🇦🇷Cordoba, Córdoba, Argentina
IMAXE
🇦🇷Buenos Aires, Argentina
Asociación de Beneficencia Hospital Sirio Libanés
🇦🇷Buenos Aires, Argentina
Centro Medico Fleischer
🇦🇷Buenos Aires, Argentina
Liga Norte Riograndense Contra o Câncer
🇧🇷Natal, RIO Grande DO Norte, Brazil
CEPHO - Centro de Estudos e Pesquisas de Hematologia e Oncologia
🇧🇷Santo André, SÃO Paulo, Brazil
Hospital Alemao Oswaldo Cruz
🇧🇷Sao Paulo, SÃO Paulo, Brazil
Fundação Faculdade Regional de Medicina de São José do Rio Preto
🇧🇷São José do Rio Preto, SÃO Paulo, Brazil
IBCC - Núcleo de Pesquisa e Ensino
🇧🇷São Paulo, Brazil
Multiprofile Hospital for Active Treatment Dr. Tota Venkova AD
🇧🇬Gabrovo, Bulgaria
"University Multiprofile Hospital for Active Treatment - Dr. Georgi Stranski" EAD
🇧🇬Pleven, Bulgaria
Complex Oncology Center - Plovdiv EOOD
🇧🇬Plovdiv, Bulgaria
Complex Oncology Center Stara Zagora EOOD
🇧🇬Stara Zagora, Bulgaria
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
Guangzhou First People's Hospital
🇨🇳Guangzhou, Guangdong, China
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Wannan Medical College Yijishan Hospital
🇨🇳Wuhu, Anhui, China
Hunan Cancer Hospital
🇨🇳Changsha, Hunan, China
Nantong Tumor Hospital
🇨🇳Nantong, Jiangsu, China
The Second Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
QEII Health Sciences Centre - Victoria General Site
🇨🇦Halifax, Nova Scotia, Canada
The First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shaanxi, China
Shandong Provincial Hospital
🇨🇳Jinan, Shandong, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, Shandong, China
Cancer Hospital Chinese Academy of Medical Science
🇨🇳Beijing, Beijing, China
The Second Affiliated Hospital of Shantou University School of Medicine
🇨🇳Shantou, Guangdong, China
The Second Affiliated Hospital of Guilin Medical University
🇨🇳Guilin, Guangxi, China
The Third Affiliated Hospital of Xinxiang Medical University
🇨🇳Xinxiang, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Inner Mongolia People's Hospital
🇨🇳Hohhot, Inner Mongolia, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
Huai'an First People's Hospital
🇨🇳Huai'an, Jiangsu, China
Shaanxi Provincial People' Hospital
🇨🇳Xi'an, Shaanxi, China
Weifang People's Hospital
🇨🇳Weifang, Shandong, China
Yantai Yuhuangding Hospital
🇨🇳Yantai, Shandong, China
Tongji Hospital of Tongji University
🇨🇳Shanghai, Shanghai, China
West China Hospital, Sichuan University
🇨🇳Cheng Du, Sichuan, China
The First Hospital of Jiaxing
🇨🇳Jiaxing, Zhejiang/nanhu, China
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou City, Zhejiang, China
The first affiliated hospital of Ningbo university
🇨🇳Ningbo, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Peking University Third Hospital
🇨🇳Beijing, China
First Affiliated Hospital of China Medical University
🇨🇳Shenyang, China
Fakultni nemocnice Olomouc
🇨🇿Olomouc, Olomoucký KRAJ, Czechia
Multiscan
🇨🇿Pardubice, Pardubický KRAJ, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿PRague, Praha 10, Czechia
Urocentrum Praha
🇨🇿Prague, Praha 2, Czechia
Fakultni Thomayerova nemocnice
🇨🇿Prague, Praha 4, Czechia
Næstved Sygehus
🇩🇰Næstved, Sjælland, Denmark
Vejle Sygehus
🇩🇰Vejle, Syddanmark, Denmark
Tampereen yliopistollinen sairaala
🇫🇮Tampere, Pirkanmaa, Finland
Oulun yliopistollinen sairaala
🇫🇮Oulu, Pohjois-pohjanmaa, Finland
Kuopion Yliopistollinen Sairaala
🇫🇮Kuopio, Pohjois-savo, Finland
Turku University Hospital
🇫🇮Turku, Varsinais-suomi, Finland
Helsinki university hospital
🇫🇮Helsinki, Finland
Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest
🇫🇷Bordeaux, Aquitaine, France
CHRU de Brest
🇫🇷Brest, Finistère, France
Centre Hospitalier Privé Saint-Grégoire
🇫🇷Saint Grégoire, Ille-et-vilaine, France
Institut de Cancérologie de l'Ouest
🇫🇷Saint Herblain, Loire-atlantique, France
Institut Jean Godinot
🇫🇷Reims, Marne, France
Clinique Victor Hugo Le Mans
🇫🇷Le Mans, Pays-de-la-loire, France
Centre Leon Berard
🇫🇷Lyon Cedex08, Rhône-alpes, France
Centre Hospitalier Lyon Sud
🇫🇷Pierre-Bénite, Rhône, France
Centre Jean Perrin - Centre Régional de Lutte contre le Cancer d'Auvergne
🇫🇷Clermont-Ferrand, France
Institut Godinot
🇫🇷Reims, France
Studienpraxis Urologie
🇩🇪Nürtingen, Baden-württemberg, Germany
Universitaetsklinikum Tuebingen
🇩🇪Tübingen, Baden-württemberg, Germany
Universitätsklinikum Münster - Albert Schweitzer Campus
🇩🇪Münster, Nordrhein-westfalen, Germany
Universitaetsklinikum Hamburg-Eppendorf
🇩🇪Hamburg, Germany
University Hospital of Patras
🇬🇷Patras, Achaḯa, Greece
Alexandra General Hospital of Athens
🇬🇷Athens, Attikí, Greece
Athens Medical Center
🇬🇷Athens, Attikí, Greece
Attikon General University Hospital
🇬🇷Chaidari, Attikí, Greece
University General Hospital of Larissa
🇬🇷Larissa, Thessalía, Greece
Borsod-Abaúj-Zemplén Vármegyei Központi Kórház és Egyetemi Oktatókórház
🇭🇺Miskolc, Borsod-abaúj-zemplén, Hungary
IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori"
🇮🇹Meldola, Emilia-romagna, Italy
Istituto Nazionale Tumori Regina Elena
🇮🇹Roma, Lazio, Italy
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore
🇮🇹Roma, Lazio, Italy
Azienda Socio Sanitaria Territoriale di Cremona
🇮🇹Cremona, Italy
Ospedale San Raffaele
🇮🇹Milano, Italy
Azienda Ospedaliera Santa Maria Terni
🇮🇹Terni, Italy
APSS- Presidio Ospedaliero S. Chiara
🇮🇹Trento, Italy
Azienda Ospedaliera Universitaria Integrata Verona - Ospedale Borgo Roma
🇮🇹Verona, Italy
Chiba cancer center
🇯🇵Chiba-shi, Chiba, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Matsuyama, Ehime, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo, Hokkaido, Japan
Hokkaido University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Kobe University Hospital
🇯🇵Kobe, Hyogo, Japan
Kanazawa University Hospital
🇯🇵Kanazawa, Ishikawa, Japan
Yokohama City University Medical Center
🇯🇵Yokohama, Kanagawa, Japan
Yokosuka Kyosai Hospital
🇯🇵Yokosuka, Kanagawa, Japan
The University of Osaka Hospital
🇯🇵Suita, Osaka, Japan
Keio university hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
National Hospital Organization Kumamoto Medical Center
🇯🇵Kumamoto, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Yamagata University Hospital
🇯🇵Yamagata, Japan
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Jeonranamdo, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Kyǒnggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Seoul-teukbyeolsi [seoul], Korea, Republic of
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Taegu-kwangyǒkshi, Korea, Republic of
Chungnam national university hospital
🇰🇷Jung-gu, Taejǒn-kwangyǒkshi, Korea, Republic of
Provita Profamilia
🇵🇱Piotrków Trybunalski, Łódzkie, Poland
CUIMED, s.r.o., Urologicka ambulancia
🇸🇰Bratislava, Slovakia
Univerzitna nemocnica Martin
🇸🇰Martin, Slovakia
MICS Centrum Medyczne Torun
🇵🇱Torun, Kujawsko-pomorskie, Poland
Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o.
🇵🇱Kraków, Małopolskie, Poland
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie
🇵🇱Kraków, Małopolskie, Poland
Clinical Best Solutions
🇵🇱Lublin, Lubelskie, Poland
Privatna urologicka ambulancia, s.r.o.
🇸🇰Trencin, Slovakia
Wits Clinical Research
🇿🇦Soweto, Gauteng, South Africa
Cancercare Langenhoven Drive Oncology Centre
🇿🇦Port Elizabeth, Eastern CAPE, South Africa
Wilgers Oncology Centre
🇿🇦Pretoria, Gauteng, South Africa
TASK Eden
🇿🇦George, Western CAPE, South Africa
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Madrid, Comunidad DE, Spain
Fundación Instituto Valenciano de Oncología
🇪🇸Valencia, Valenciana, Comunitat, Spain
Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
Södersjukhuset
🇸🇪Stockholm, Stockholms LÄN [se-01], Sweden
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳Kaohsiung, Taiwan
Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Koç Üniversitesi Hastanesi
🇹🇷İstanbul, İ̇stanbul, Turkey
Memorial Ankara Hastanesi
🇹🇷Ankara, Turkey
Royal Blackburn Hospital
🇬🇧Blackburn, Blackburn WITH Darwen, United Kingdom
The Beatson West of Scotland Cancer Centre
🇬🇧Glasgow, United Kingdom