Metastatic Castration Resistant Prostate Cancer (mCRPC)Phase 1NCT03460977
A Study of Mevrometostat for Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
A Phase 1 study testing Mevrometostat (PF-06821497), Enzalutamide and Itraconazole in people with Metastatic Castration Resistant Prostate Cancer (mCRPC) and Small Cell Lung Cancer (SCLC), run by Pfizer at 85 sites in 8 countries.
Trial summary
The purpose of this study is to learn about the safety and effects of the study medicine (called Mevrometostat) for the possible treatment of Relapsed/ Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) and Follicular Lymphoma (FL). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)
- What is being tested?
- Mevrometostat (PF-06821497), Enzalutamide and Itraconazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 453 participants
- Where
- 85 sitesin 8 countries
- Study dates
- 17 Apr 2018to 7 Jul 2029
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Part 1 and Part 2 (Closed for enrollment).
Part 3 Key Inclusion Criteria:
- Histological or cytological diagnosis of castration resistant prostate cancer.
- Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-2 with expected life expectancy of at least 6 months.
- Adequate bone marrow, renal, and liver function
Part 3 Key Exclusion Criteria:
- Prior irradiation to >25% of the bone marrow.
- QTcF interval >480 msec at screening.
- Hypertension that cannot be controlled by medications (>150/90 mmHg despite optimal medical therapy).
- Known or suspected hypersensitivity to PF 06821497 or any components or enzalutamide (CRPC)
- Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular disease or previous gastric resection or lap band surgery.
- Current use or anticipated need for food or drugs that are known strong and moderate CYP3A4/5 inducers or inhibitors
- Prior enzalutamide within the last 4 weeks
- DDI SUBSTUDY:
- history of CHF or evidence of ventricular dysfunction
- fructose intolerance
- coadministration of CYP3A4 substrates
Trial locations and contacts
85 sites in 8 countries. Contact the study team or a site near you to ask about taking part.
85 sites in 8 countries
United States45 sites, 9 recruiting
- Active, not recruiting
Pacific Cancer Medical Center INC
Anaheim, California, 92801
- Terminated
Texas Oncology - Austin Midtown
Austin, Texas, 78705
- Active, not recruiting
Brigham and Women's Hospital
Boston, Massachusetts, 02115
- Active, not recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Active, not recruiting
University of Texas Southwestern Medical Center - Simmons Cancer Center
Dallas, Texas, 75390
- Active, not recruiting
UT Southwestern Medical Center
Dallas, Texas, 75390
- Active, not recruiting
UT Southwestern University Hospital - William P. Clements, Jr
Dallas, Texas, 75390
- Active, not recruiting
UT Southwestern University Hospital - Zale Lipshy
Dallas, Texas, 75390
- Active, not recruiting
City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
Duarte, California, 91010
- Active, not recruiting
City of Hope Investigational Drug Services (IDS)
Duarte, California, 91010
- Active, not recruiting
Virginia Cancer Specialists, PC
Fairfax, Virginia, 22031
- Active, not recruiting
The University of Kansas Cancer Center, Investigational Drug Services
Fairway, Kansas, 66205
- Active, not recruiting
The University of Kansas Clinical Research Center
Fairway, Kansas, 66205
- Active, not recruiting
Hackensack University Medical Center
Hackensack, New Jersey, 07601
- Active, not recruiting
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, 07601
- Recruiting
NEXT Dallas
Irving, Texas, 75039
- Terminated
US Oncology Investigational Product Center (IPC)
Irving, Texas, 75063
- Terminated
US Oncology Investigational Products Center
Irving, Texas, 75063
- Active, not recruiting
The University of Kansas Hospital
Kansas City, Kansas, 66160
- Active, not recruiting
The University of Kansas Medical Center Medical Office Building
Kansas City, Kansas, 66160
- Active, not recruiting
Norton Cancer Institute - Downtown
Louisville, Kentucky, 40202
- Active, not recruiting
Norton Cancer Institute, Norton Healthcare Pavilion
Louisville, Kentucky, 40202
- Active, not recruiting
Norton Hospital
Louisville, Kentucky, 40202
- Recruiting
Carolina Urologic Research Center
Myrtle Beach, South Carolina, 29572
- Recruiting
Parkway Surgery Center
Myrtle Beach, South Carolina, 29572
- Recruiting
Sarah Cannon Research Institute - Pharmacy
Nashville, Tennessee, 37203
- Recruiting
SCRI Oncology Partners
Nashville, Tennessee, 37203
- Active, not recruiting
Dana Farber Cancer Institute- Chestnut Hill
Newton, Massachusetts, 02459
- Active, not recruiting
Norwalk Hospital
Norwalk, Connecticut, 06856
- Recruiting
OU Health University of Oklahoma Medical Center
Oklahoma City, Oklahoma, 73104
- Recruiting
Stephenson Cancer Center (chemo location)
Oklahoma City, Oklahoma, 73104
- Recruiting
Oncology Hematology West, PC dba Nebraska Cancer Specialists
Omaha, Nebraska, 68130
- Active, not recruiting
The University of Kansas Cancer Center - Indian Creek Campus
Overland Park, Kansas, 66211
- Active, not recruiting
Olympic Medical Center
Port Angeles, Washington, 98362
- Active, not recruiting
Fred Hutchinson Cancer Center Alliance Peninsula
Poulsbo, Washington, 98370
- Terminated
Maryland Oncology Hematology, P.A.
Rockville, Maryland, 20850
- Recruiting
NEXT Oncology
San Antonio, Texas, 78229
- Active, not recruiting
NEXT Oncology
San Antonio, Texas, 78240
- Active, not recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
- Active, not recruiting
University of Washington Medical Center
Seattle, Washington, 98109
- Active, not recruiting
Banner-University Medical Center Tucson
Tucson, Arizona, 85719
- Active, not recruiting
The University of Arizona Cancer Center-North Campus
Tucson, Arizona, 85719
- Active, not recruiting
The University of Arizona Cancer Center
Tucson, Arizona, 85724
- Terminated
Arizona Urology Specialists, PLLC
Tucson, Arizona, 85741
- Active, not recruiting
The University of Kansas Cancer Center
Westwood, Kansas, 66205
Spain13 sites, 10 recruiting
- Recruiting
Hospital Quironsalud Barcelona
Barcelona, 08023
- Recruiting
Hospital Universitari Vall d'Hebron
Barcelona, 08035
- Recruiting
Hospital Clinic de Barcelona
Barcelona, 08036
- Active, not recruiting
Consorcio Hospitalario Provincial de Castellon
Castellon, Castellon, 12002
- Active, not recruiting
Institut Català d´Oncología (ICO)-H. Durán i Reynals
L'Hospitalet de Llobregat, Barecelona, 08908
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
- Recruiting
H.U. Fundación Jiménez Díaz
Madrid, 28040
- Recruiting
Hospital Clinico San Carlos
Madrid, 28040
- Recruiting
Hospital Universitario 12 De Octubre
Madrid, 28041
- Recruiting
Hospital Universitario HM Sanchinarro
Madrid, 28050
- Recruiting
Hospital Universitario Virgen de la Victoria
Málaga, 29010
- Recruiting
Hospital Quironsalud Madrid
Pozuelo de Alarcón, Madrid, 28223
- Active, not recruiting
Hospital Universitari i Politecnic La Fe
Valencia, 46026
Russia9 sites
- Active, not recruiting
LLC "Neyro-klinika"
Moscow, 117186
- Terminated
Moscow GBUZ "City clinical hospital n. a. S.P. Botkina" of Moscow health department
Moscow, 125284
- Terminated
SBHI of Moscow City Clinical Hospital
Moscow, 129301
- Terminated
Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"
Omsk, 644013
- Active, not recruiting
Private Medical Institution "Euromedservice"
Pushkin, Sankt-Peterburg, 196603
- Terminated
Federal State Budgetary Institution National Medical Research Center n.a. V.A. Almazov
Saint Petersburg, 197341
- Terminated
Federal State Budgetary Institution National Medical Research Center for Oncology n.a. N.N.
Saint Petersburg, 197758
- Terminated
Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"
Saint Petersburg, 198255
- Terminated
State Budgetary Healthcare Institution of the Yaroslavl Region
Yaroslavl, 150054
China6 sites, 1 recruiting
- Active, not recruiting
Hunan Cancer Hospital
Changsha, Hunan, 410013
- Recruiting
West China Hospital, Sichuan University
Chengdu, Sichuan, 610041
- Active, not recruiting
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
- Active, not recruiting
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
Nanjing, Jiangsu, 210008
- Active, not recruiting
Zhongda Hospital Southeast University
Nanjing, Jiangsu, 210009
- Active, not recruiting
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000
Poland5 sites, 2 recruiting
- Not yet recruiting
In-Vivo Sp. z o.o. In-vivo Bydgoszcz
Bydgoszcz, 85-048
- Active, not recruiting
Szpital Wojewódzki im. Mikołaja Kopernika w Koszalinie
Koszalin, 75-581
- Recruiting
Centrum Badań Klinicznych Jagiellońskie Centrum Innowacji sp. z o.o.
Krakow, 30-348
- Active, not recruiting
Centrum Medyczne MEDYK
Rzeszów, 35-326
- Active, not recruiting
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
Warsaw, 02-781
South Korea5 sites, 1 recruiting
- Active, not recruiting
Chungnam national university hospital
Daejeon, Taejǒn-kwangyǒkshi, 35015
- Recruiting
Seoul National University Bundang Hospital
Seongnam, Kyǒnggi-do, 13620
- Active, not recruiting
Seoul National University Hospital
Seoul, Seoul-teukbyeolsi [seoul], 03080
- Active, not recruiting
Severance Hospital, Yonsei University Health System
Seoul, Seoul-teukbyeolsi [seoul], 03722
- Active, not recruiting
Ewha Womans University Mokdong Hospital
Seoul, Seoul-teukbyeolsi [seoul], 07985
Bulgaria1 site
- Terminated
Specialized Hospital for Active Treatment of Oncology - Haskovo
Haskovo, 6300
Japan1 site
- Active, not recruiting
National Cancer Center Hospital East
Kashiwa, Chiba, 277-8577
About this study
Official title: A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF 06821497 (MEVROMETOSTAT) IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)
The purpose of this study is to learn about the safety and effects of the study medicine (called Mevrometostat) for the possible treatment of Relapsed/ Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) and Follicular Lymphoma (FL). The study consists of 3 parts; Part 1 and 2 enrolled participants with SCLC, metastatic CRPC, and FL are closed for enrollment.
Part 3, which is open for enrollment is seeking men who:
Read more
- have Castration Resistant Prostate Cancer (CRPC) and
- have previously received treatment for CRPC and have progressed from the last treatment
All participants in Part 3 of this study will receive mevrometostat and/ or enzalutamide. Part 3 consists of 2 sub studies each has an assessment phase and a maintenance phase. The Part 3 DDI substudy consist of 2 cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (Combination cohort).
In the assessment phase:
- participants in the BE substudy will take 3 single doses of mevrometostat by mouth over 3 periods.
- participants in the DDI substudy Cohort 1 (monotherapy cohort) will take mevrometostat 2 times a day and/or itraconazole 1 time a day based on a present schedule.
- participants in the DDI substudy Cohort 2 (combination cohort) will take mevrometostat 2 times a day, enzalutamide 1 time a day, and/or itraconazole 1 time a day based on a present schedule.
After completion of the assessment phase, participants will enter the maintenance phase where they will receive mevrometostat 2 times a day and enzalutamide 1 time a day by mouth until their cancer is no longer responding.
The study will look at the experiences of participanrs receiving the study medicine. This will help see if the study medicine is safe and effective.
Read the detailed description
This is an open label, multi center, Phase 1 dose escalation and dose expansion study of mevrometostat (PF-06821497) administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. The study consists of three parts (Part 1, Part 2, and Part 3) along with the Japan and China monotherapy cohorts. Part 1 and Part 2 are closed for enrollment. Part 1 tested monotherapy in 3 cohorts (Parts 1A, 1B, and 1C); Part 2 tested combination therapy in Parts 2A (dose escalation), 2B and 2C (does expansion).
Part 3 consists of the Bioequivalence (BE) and drug-drug interaction (DDI) substudies and are open for enrollment. The BE substudy will test between 2 mevrometostat formulation to confirm that they work in the body the same way. The DDI substudy will evaluate the effect of a strong CYP3A4 (an enzyme in your body that breaks down/ removes drugs) inhibitor on the PK of mevrometostat; a strong CYP3A4 inhibitor may slow down the breakdown/ removal of drugs in your body. The Sponsor may choose to delay or discontinue any cohorts or substudies.
- Conditions
- Metastatic Castration Resistant Prostate Cancer (mCRPC), Small Cell Lung Cancer (SCLC), Follicular Lymphoma (FL)
- Being tested
- Mevrometostat (PF-06821497), Enzalutamide, Itraconazole
- Keywords
- EZH2, enhancer of zeste homolog 2, castrate resistant prostate cancer, prostatecancer-study.com, mCRPC, efficacy, safety, pharmacokinetics, pharmacodynamics, dose escalation, dose expansion, open-label, small cell lung cancer, SCLC, follicular lymphoma, FL, relapsed, refractory
- Medical subject headings
- Small Cell Lung Carcinoma, Lymphoma, Follicular, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mevrometostat (PF-06821497)Drug
Also called EZH2i
Oral continuous
EnzalutamideDrug
Also called Xtandi
Oral continuous
ItraconazoleDrug
Also called Sporanox, Tolsura, Onmel
Oral solution
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation (Part 1A) | Experimental | Participants with SCLC, CRPC and FL will receive mevrometostat at escalating dose levels Receives: Drug: Mevrometostat (PF-06821497) |
| Dose Escalation (Part 1B) | Experimental | Participants with FL will receive mevrometostat at escalating dose levels Receives: Drug: Mevrometostat (PF-06821497) |
| Dose Escalation (Part 1C) | Experimental | Participants with mCRPC will receive mevrometostat at escalating dose levels. Receives: Drug: Mevrometostat (PF-06821497) |
| Dose Escalation (Part 2A) | Experimental | Participants with mCRPC and SCLC will receive mevrometostat at escalating dose levels in combination with SOC. Receives: Drug: Mevrometostat (PF-06821497); Drug: Enzalutamide |
| Dose Expansion (Part 2B) | Experimental | Participants with CRPC will receive mevrometostat in combination with SOC or SOC alone. Receives: Drug: Mevrometostat (PF-06821497); Drug: Enzalutamide |
| Japan Cohort | Experimental | Participants with CRPC will receive mevrometostat at one or two doses Receives: Drug: Mevrometostat (PF-06821497) |
| China cohort | Experimental | Participants will receive mevrometostat at one or two doses Receives: Drug: Mevrometostat (PF-06821497) |
| Dose Expansion (Part 2C) | Experimental | Participants with mCRPC will receive mevrometostat at a different dose/dosing regimen than that of Part 2B in combination with SOC Receives: Drug: Mevrometostat (PF-06821497); Drug: Enzalutamide |
| BE Substudy | Experimental | In the assessment phase, each enrolled participant will receive single doses of the 2 different mevrometostat formulations in 3 periods with alternating dosing and washout between each dose. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day. Receives: Drug: Mevrometostat (PF-06821497); Drug: Enzalutamide |
| DDI Substudy | Experimental | The DDI substudy assessment phase will consist of 2 Cohorts, Cohort 1 (monotherapy cohort) and Cohort 2 (combination cohort). In the Cohort 1 assessment phase, each enrolled participant will receive a combination of mevrometostat and itraconazole based on preset schedule. In the Cohort 2 assessment phase, each enrolled participant will receive a combination of mevrometostat, enzalutamide, and itraconazole based on preset schedule. In the maintenance phase, each participant will receive mevrometostat 2 times a day and enzalutamide 1 time a day. Receives: Drug: Mevrometostat (PF-06821497); Drug: Enzalutamide; Drug: Itraconazole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
First cycle DLTs will be utilized to determine the MTD
Measured: Baseline up to 90 days
Overall safety profile including adverse events
Adverse Events will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE version [4.03])
Measured: Baseline up to approximately 2 years
Preliminary efficacy determination as evaluated by disease specific response criteria
Objective response using Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC). Progression-free survival in Part 2B in patients with CRPC.
Measured: Through study completion, approximately 2 years past last patient first visit.
Overall safety profile including laboratory abnormalities
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version [4.03]), and timing.
Measured: Baseline up to approximately 2 years
Overall safety profile including vital signs
Vital sign changes from baseline including blood pressure, heart rate, ECG changes.
Measured: Baseline up to approximately 2 years
Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival
PCWG3
Measured: Baseline until disease progression or death or through study completion (approx 2 years)
Secondary outcomes (10)
Evaluate time to event anti-tumor activity of mevrometostat including progression-free survival (PFS), PSA50, Duration of Response (DoR), Time to first skeletal related event and Time to symptomatic skeletal related event, depending on tumor type.
Time to event endpoints based on Response Evaluation Criteria in Lymphoma (RECIL) for lymphoma, Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 for solid tumors including Small Cell Lung Cancer (SCLC) and Prostate Cancer Working Group 3 (PCWG3) for Castration Resistant Prostate Cancer (CRPC)
Measured: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.
Evaluate overall survival
Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.
Measured: Baseline up to approximately 2 years
Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
Single dose and multiple dose PK will be calculated as data permits
Measured: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)
Single dose and multiple dose PK will be calculated as data permits
Measured: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Area Under the Curve (AUC)
Single dose and multiple dose PK will be calculated as data permits
Measured: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)
Single dose and multiple dose PK will be calculated as data permits
Measured: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)
Single dose and multiple dose PK will be calculated as data permits
Measured: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)
Singe dose and multiple dose PK will be calculated as data permits
Measured: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Evaluate the impact of mevrometostat on patient reported outcomes.
Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.
Measured: At specific time-points from Cycle 1 Day 1 to End of Treatment visit.
Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity
Questionnaire customized from PRO-CTCAE.
Measured: At specific time points from Cycle1 Day 1 to end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Mar 2018
- Study start17 Apr 2018
- Primary completion20 Apr 2028 (estimated)
- Study completion7 Jul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Castration Resistant Prostate Cancer (mCRPC)Studies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 453 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03460977
- Sponsor's protocol ID
- C2321001
- Other IDs
- EZH2, 2023-509179-18-00, 2023
- Status last verified
- Oct 2026
- First submitted
- 12 Feb 2018
- Last updated
- 15 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: 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.