Clinical trial NCT03460977: Mevrometostat Treatment of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Metastatic Castration Resistant Prostate Cancer (mCRPC)
Small Cell Lung Cancer (SCLC)
Follicular Lymphoma (FL)
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
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2018-03-09
Enrollment: 343
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: A Phase 1 Dose Escalation and Expanded Cohort Study Of PF-06821497 (Mevrometostat) in Adult Patients With Relapsed/Refractory Small Cell Lung Cancer (SCLC), Castration Resistant Prostate Cancer (CRPC) And Follicular Lymphoma (FL).

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 Part 1, Part 2 and the Japan and China monotherapy cohorts Part 1A will evaluate safety and target modulation of mevrometostat monotherapy in patients with SCLC, FL and CRPC. Mevrometostat will be administered as monotherapy in escalating doses to patients with FL (Part 1B) and mCRPC (Part 1C) to determine the monotherapy MTD. In Part 2A (dose escalation, RP2D finding for dose escalation), mevrometostat will be administered in combination with SOC to patients with mCRPC and SCLC. Japan and China monotherapy cohorts will evaluate the safety, antitumor activity and PK of single agent mevrometostat in Japanese and Chinese patients. In Part 2B (dose expansion), patients with mCRPC will be randomized (1:1 ratio) to receive either SOC or mevrometostat in combination with SOC. Part 2B will assess the efficacy of mevrometostat at the RP2D in combination with SOC in patients with mCRPC in comparison to SOC alone. Part 2C will explore the efficacy of mevrometostat given at a different dose/dosing regimen than 2B in combination with SOC in patients with mCRPC.

Eligibility criteria: Key Inclusion Criteria:

Histological or cytological diagnosis of advanced / metastatic solid tumor with the following tumor types in individual study parts:

Part 1A (closed to enrollment):

Part 1B (closed to enrollment):

Part 1C:

* Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) Japan cohort
* Castration resistant prostate cancer that is resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3) China cohort
* Castration resistant prostate cancer that is intolerant/resistant to SOC or for which no local regulatory approved SOC is available that would confer significant clinical benefit in the medical judgement of the investigator. Patients who refused SOC may be eligible. Patients should have received either abiraterone and/or enzalutamide treatment and have evidence of prostate cancer progression (per PCWG3)

Part 2A:

• Metastatic Castration resistant prostate cancer. Patients should have received either abiraterone and/or enzalutamide treatment, may have received up to 1 line of chemotherapy and have evidence of prostate cancer progression (per PCWG3)

Part 2B/2C:

* Metastatic Castration resistant prostate cancer. Patients should have received abiraterone treatment, may have received up to 1 prior line of chemotherapy, have not received prior enzalutamide, apalutamide or darolutamide and have evidence of prostate cancer progression (per PCWG3)
* Patients must have radiographic evidence of disease

Other inclusion criteria:

-Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1.

Key Exclusion Criteria:

- Prior Chemotherapy: Part 1C , Japan cohort and China cohort (CRPC): no more than 2 previous regimens of chemotherapy Part 2A: mCRPC: no more than 1 previous regimen of systemic chemotherapy Part 2B (mCRPC): no more than 1 previous regimen of chemotherapy

* 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. Gastroesophageal reflux disease under treatment with proton pump inhibitors is allowed.
* Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inducers or inhibitors, including their administration within 10 days or 5 half lives of the CYP3A4/5 inhibitor, whichever is longer prior to first dose of investigational product.

Primary outcomes:
measure: Percentage of patients with dose limiting toxicities (DLTs) to determine the maximum tolerated dose (MTD)
timeFrame: Baseline up to 90 days
measure: Overall safety profile including adverse events
timeFrame: Baseline up to approximately 2 years
measure: Preliminary efficacy determination as evaluated by disease specific response criteria
timeFrame: Through study completion, approximately 2 years past last patient first visit.
measure: Overall safety profile including laboratory abnormalities
timeFrame: Baseline up to approximately 2 years
measure: Overall safety profile including vital signs
timeFrame: Baseline up to approximately 2 years
measure: Evaluate time to event mevrometostat and enzalutamide vs enzalutamide alone including radiographic prgression free survival
timeFrame: Baseline until disease progression or death or through study completion (approx 2 years)
Secondary outcomes:
measure: 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.
timeFrame: Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.
measure: Evaluate overall survival
timeFrame: Baseline up to approximately 2 years
measure: Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)
timeFrame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
measure: Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
measure: Pharmacokinetic Parameters: Area Under the Curve (AUC)
timeFrame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
measure: Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)
timeFrame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
measure: Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)
timeFrame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
measure: Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)
timeFrame: At specific timepoints from Cycle 1 day 1 to End of Treatment visit
measure: Evaluate the impact of mevrometostat on patient reported outcomes.
timeFrame: At specific time-points from Cycle 1 Day 1 to End of Treatment visit.
measure: Impact of mevrometostat in combination with enzalutamide, enzalutamide alone and mevrometostat alone on symptoms and symptomatic toxicity
timeFrame: At specific time points from Cycle1 Day 1 to end of treatment
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, P.C .
state: Arizona
city: Tucson
country: United States
facility: Banner-University Medical Center Tucson
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center-North Campus
state: Arizona
city: Tucson
country: United States
facility: The University of Arizona Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Urological Associates of Southern Arizona, PC
state: Arizona
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center INC
state: California
city: Duarte
country: United States
facility: City of Hope (City of Hope National Medical Center, City of Hope Medical Center)
state: California
city: Duarte
country: United States
facility: City of Hope Investigational Drug Services (IDS)
state: California
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Fairway
country: United States
facility: The University of Kansas Cancer Center, Investigational Drug Services
state: Kansas
city: Fairway
country: United States
facility: The University of Kansas Clinical Research Center
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Hospital
state: Kansas
city: Kansas City
country: United States
facility: The University of Kansas Medical Center Medical Office Building
state: Kansas
city: Overland Park
country: United States
facility: The University of Kansas Cancer Center - Indian Creek Campus
state: Kansas
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Louisville
country: United States
facility: Norton Cancer Institute Pharmacy, Downtown Pharmacy
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute Pharmacy
state: Kentucky
city: Louisville
country: United States
facility: Norton Cancer Institute, Norton Healthcare Pavilion
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital
state: Kentucky
city: Rockville
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Omaha
country: United States
facility: Oncology Hematology West, PC dba Nebraska Cancer Specialists
state: Nebraska
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Oklahoma City
country: United States
facility: OU Medical Center Presbyterian Tower
state: Oklahoma
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Myrtle Beach
country: United States
facility: Parkway Surgery Center
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncolgy, PLLC
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology, PLLC
state: Tennessee
city: Nashville
country: United States
facility: The Sarah Cannon Research Institute
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Midtown
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center - Simmons Cancer Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern University Hospital - William P. Clements, Jr
state: Texas
city: Dallas
country: United States
facility: UT Southwestern University Hospital - Zale Lipshy
state: Texas
city: Irving
country: United States
facility: US Oncology Investigational Product Center (IPC)
state: Texas
city: Irving
country: United States
facility: US Oncology Investigational Products Center
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Haskovo
country: Bulgaria
facility: Specialized Hospital for Active Treatment of Oncology - Haskovo
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
state: Jiangsu
city: Cheng Du
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
state: Kyǒnggi-do
city: Gangnam-gu
country: Korea, Republic of
facility: Gangnam Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Seoul-teukbyeolsi [seoul]
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
state: Seoul-teukbyeolsi [seoul]
city: Daejeon
country: Korea, Republic of
facility: Chungnam national university hospital
state: Taejǒn-kwangyǒkshi
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Mikołaja Kopernika w Koszalinie
city: Koszalin
country: Poland
facility: Centrum Diagnostyczne Affidea Koszalin
city: Rzeszow
country: Poland
facility: Centrum Medyczne MEDYK
city: Warszawa
country: Poland
facility: LUX MED Onkologia Sp. z o.o. Szpital Szamocka
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie
city: Pushkin
country: Russian Federation
facility: Private Medical Institution "Euromedservice"
state: Saint - Petersburg
city: Moscow
country: Russian Federation
facility: LLC "Neyro-klinika"
city: Moscow
country: Russian Federation
facility: Moscow GBUZ "City clinical hospital n. a. S.P. Botkina" of Moscow health department
city: Moscow
country: Russian Federation
facility: SBHI of Moscow City Clinical Hospital
city: Omsk
country: Russian Federation
facility: Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"
city: Saint Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution National Medical Research Center n.a. V.A. Almazov
city: Saint Petersburg
country: Russian Federation
facility: Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"
city: Saint-Petersburg
country: Russian Federation
facility: Non-governmental Healthcare Institution ¨Railway Clinical Hospital of JSC ¨Russian Railways¨
city: Saint-Petersburg
country: Russian Federation
facility: Federal State Budgetary Institution National Medical Research Center for Oncology n.a. N.N.
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Healthcare Institution of the Yaroslavl Region
city: L'Hospitalet de Llobregat
country: Spain
facility: Institut Català d´Oncología (ICO)-H. Durán i Reynals
state: Barecelona
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quironsalud Madrid
state: Madrid
city: Barcelona
country: Spain
facility: Hospital Quironsalud Barcelona
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Castellon
country: Spain
facility: Consorcio Hospitalario Provincial de Castellon
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: H.U. Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 De Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: València
country: Spain
facility: Hospital Universitari i Politecnic La Fe
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: