PF-06821497 Treatment Of Relapsed/Refractory SCLC, Castration Resistant Prostate Cancer, and Follicular Lymphoma

Follicular Lymphoma (FL) Clinical Trial

Official title:

A PHASE I DOSE ESCALATION AND EXPANDED COHORT STUDY OF PF-06821497 IN THE TREATMENT OF ADULT PATIENTS WITH RELAPSED/REFRACTORY SMALL CELL LUNG CANCER (SCLC), CASTRATION RESISTANT PROSTATE CANCER (CRPC) AND FOLLICULAR LYMPHOMA (FL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03460977
• Other study ID #: C2321001
• Secondary ID: 2018-001835-37
• Status: Recruiting
• Phase: Phase 1
• Start date: April 17, 2018
• Est. completion date: October 24, 2025

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: Pfizer CT.gov Call Center
• Phone: 1-800-718-1021
• Email: ClinicalTrials.gov_Inquiries[@]pfizer.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

This is an open label, multi center, Phase 1 dose escalation and dose expansion study of PF-06821497 administered orally BID as a single agent or in combination with SOC to patients with CRPC, SCLC, and FL. Part 1A will evaluate safety and target modulation of PF-06821497 monotherapy in patients with SCLC, FL and CRPC. PF-06821497 will be administered as monotherapy in patients with FL in Part 1B dose escalation and to patients with CRPC in Part 1C dose escalation. For Part 2A (dose escalation combination therapy), PF-06821497 will be administered in combination with SOC in patients with CRPC and SCLC. For Part 2B (dose expansion), patients with mCRPC will be randomized (1:1 ratio) to receive either SOC or PF-06821497 in combination with SOC. Once safety and adequate target modulation has been established in Part 1A, Parts 1B and 2A of the trial will be initiated. Part 1C (monotherapy dose escalation) will determine the MTD of single agent PF-06821497 in patients with mCRPC. Japan and China monotherapy cohorts will evaluate the safety, antitumor activity and PK of single agent PF-06821497 in Japanese and Chinese patients. Part 2A (escalation RP2D finding for combination) will determine the MTD of the combination with SOC in patients with CRPC. Part 2B (dose expansion) will assess the efficacy of PF-06821497 at the RP2D in combination with SOC in patients with mCRPC in comparison to SOC alone. The study is currently enrolling Part 2B.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 267
• Est. completion date: October 24, 2025
• Est. primary completion date: October 24, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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:

• 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:

• 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:

• 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.
• Adequate organ function

Key Exclusion Criteria:

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

Related Conditions & MeSH terms

• Castration Resistant Prostate Cancer (CRPC)
• Follicular Lymphoma (FL)
• Lung Neoplasms
• Lymphoma
• Lymphoma, Follicular
• Prostatic Neoplasms
• Small Cell Lung Cancer (SCLC)
• Small Cell Lung Carcinoma

Intervention

Drug:
• PF-06821497
Oral continuous

Locations

Country	Name	City	State
Bulgaria	Specialized Hospital for Active Treatment of Oncology - Haskovo	Haskovo
Bulgaria	Complex Oncology Center - Plovdiv EOOD	Plovdiv
Bulgaria	Complex Oncology Center - Ruse EOOD	Ruse
Bulgaria	"Complex Oncology Center - Vratsa" EOOD	Vratsa
China	Hunan Cancer Hospital	Changsha	Hunan
China	West China Hospital, Sichuan University	Cheng Du	Sichuan
China	West China Hospital, Sichuan University	Cheng Du	Sichuan
China	The First Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong
China	Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu	Taegu-kwangyokshi
Korea, Republic of	Chungnam national university hospital	Daejeon	Taejon-kwangyokshi
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Gangnam-gu	Seoul-teukbyeolsi [seoul]
Korea, Republic of	National Cancer Center	Goyang-si	Kyonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Kyonggi-do
Korea, Republic of	Asan Medical Center	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Ewha Womans University Mokdong Hospital	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Gangnam Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Samsung Medical Center	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul-teukbyeolsi [seoul]
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [seoul]
Poland	Centrum Diagnostyczne Affidea Koszalin	Koszalin
Poland	Szpital Wojewódzki im. Mikolaja Kopernika w Koszalinie	Koszalin
Poland	Centrum Medyczne MEDYK	Rzeszow
Poland	Centrum Medyczne MEDYK	Rzeszow
Poland	LUX MED Onkologia Sp. z o.o. Szpital Szamocka	Warszawa
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie	Warszawa
Russian Federation	LLC "Neyro-klinika"	Moscow
Russian Federation	Moscow GBUZ "City clinical hospital n. a. S.P. Botkina" of Moscow health department	Moscow
Russian Federation	SBHI of Moscow City Clinical Hospital	Moscow
Russian Federation	Budgetary Healthcare Institution of Omsk region "Clinical Oncological Dispensary"	Omsk
Russian Federation	Private Healthcare Institution "Clinical hospital "RZD-Medicine" of Saint-Petersburg	Pushkin	Saint Petersburg
Russian Federation	Private medical institution "Euromedservice"	Pushkin	Saint-petersburg
Russian Federation	Private Medical Institution "Euromedservice"	Pushkin	Saint - Petersburg
Russian Federation	Federal State Budgetary Institution National Medical Research Center n.a. V.A. Almazov	Saint Petersburg
Russian Federation	Saint Petersburg State Budgetary Healthcare Institution "City Clinical Oncological Dispensary"	Saint Petersburg
Russian Federation	Federal State Budgetary Institution National Medical Research Center for Oncology n.a. N.N.	Saint-Petersburg
Russian Federation	Non-governmental Healthcare Institution ¨Railway Clinical Hospital of JSC ¨Russian Railways¨	Saint-Petersburg
Russian Federation	Private Healthcare Institution "Clinical hospital "RZD-Medicine" of Saint-Petersburg	Saint-Petersburg
Russian Federation	State Budgetary Healthcare Institution of the Yaroslavl Region	Yaroslavl
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona
Spain	Hospital HM Nou Delfos	Barcelona
Spain	Hospital Quironsalud Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Consorcio Hospitalario Provincial de Castellon	Castellon
Spain	Institut Català d´Oncología (ICO)-H. Durán i Reynals	L'Hospitalet de Llobregat	Barecelona
Spain	H.U. Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario 12 De Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Hospital Quironsalud Madrid	Pozuelo de Alarcon	Madrid
Spain	Hospital Universitari i Politecnic La Fe	València
United States	Pacific Cancer Medical Center INC	Anaheim	California
United States	Texas Oncology - Austin Midtown	Austin	Texas
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	University of Texas Southwestern Medical Center - Simmons Cancer Center	Dallas	Texas
United States	University of Texas Southwestern Medical Center-Simmons Cancer Center Pharmacy	Dallas	Texas
United States	UT Southwestern Medical Center	Dallas	Texas
United States	UT Southwestern Simmons Cancer Center	Dallas	Texas
United States	UT Southwestern University Hospital - William P. Clements, Jr	Dallas	Texas
United States	UT Southwestern University Hospital - Zale Lipshy	Dallas	Texas
United States	City of Hope (City of Hope National Medical Center, City of Hope Medical Center)	Duarte	California
United States	City of Hope Investigational Drug Services (IDS)	Duarte	California
United States	Virginia Cancer Specialists, PC	Fairfax	Virginia
United States	The University of Kansas Cancer Center, Investigational Drug Services	Fairway	Kansas
United States	The University of Kansas Clinical Research Center	Fairway	Kansas
United States	Texas Oncology -Fort Worth Cancer Center	Fort Worth	Texas
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	US Oncology Investigational Product Center (IPC)	Irving	Texas
United States	US Oncology Investigational Product Center (IPC)	Irving	Texas
United States	US Oncology Investigational Products Center	Irving	Texas
United States	The University of Kansas Hospital	Kansas City	Kansas
United States	The University of Kansas Medical Center Medical Office Building	Kansas City	Kansas
United States	Norton Cancer Institute Pharmacy	Louisville	Kentucky
United States	Norton Cancer Institute Pharmacy, Downtown Pharmacy	Louisville	Kentucky
United States	Norton Cancer Institute, Norton Healthcare Pavilion	Louisville	Kentucky
United States	Norton Hospital	Louisville	Kentucky
United States	Carolina Urologic Research Center	Myrtle Beach	South Carolina
United States	Parkway Surgery Center	Myrtle Beach	South Carolina
United States	Tennessee Oncolgy, PLLC	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	The Sarah Cannon Research Institute	Nashville	Tennessee
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Norwalk Hospital	Norwalk	Connecticut
United States	OU Medical Center Presbyterian Tower	Oklahoma City	Oklahoma
United States	Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Oncology Hematology West, PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	The University of Kansas Cancer Center - Indian Creek Campus	Overland Park	Kansas
United States	Illinois CancerCare, P.C.	Peoria	Illinois
United States	Maryland Oncology Hematology, P.A.	Rockville	Maryland
United States	NEXT Oncology	San Antonio	Texas
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Banner-University Medical Center Tucson	Tucson	Arizona
United States	The University of Arizona Cancer Center	Tucson	Arizona
United States	The University of Arizona Cancer Center-North Campus	Tucson	Arizona
United States	Urological Associates of Southern Arizona, P.C .	Tucson	Arizona
United States	Urological Associates of Southern Arizona, PC	Tucson	Arizona
United States	The University of Kansas Cancer Center	Westwood	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Bulgaria,  China,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Baseline up to 90 days
Primary	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])	Baseline up to approximately 2 years
Primary	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.	Through study completion, approximately 2 years past last patient first visit.
Primary	Overall safety profile including laboratory abnormalities	Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version [4.03]), and timing.	Baseline up to approximately 2 years
Primary	Overall safety profile including vital signs	Vital sign changes from baseline including blood pressure, heart rate, ECG changes.	Baseline up to approximately 2 years
Secondary	Evaluate time to event anti-tumor activity of PF-06821497 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)	Baseline and every 21 days through time of confirmed disease progression, unacceptable toxicity, or through study completion, approximately 2 years.
Secondary	Evaluate overall survival	Median time to death proportion of patients alive at 6 months, 1 year, and 2 years.	Baseline up to approximately 2 years
Secondary	Pharmacokinetic Parameters: Maximum Observed Plasma Concentration (Cmax)	Single dose and multiple dose PK will be calculated as data permits	At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Secondary	Pharmacokinetic Parameters: Time to Reach Maximum Observed Plasma Concentration (Tmax)	Single dose and multiple dose PK will be calculated as data permits	At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Secondary	Pharmacokinetic Parameters: Area Under the Curve (AUC)	Single dose and multiple dose PK will be calculated as data permits	At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Secondary	Pharmacokinetic Parameters: Apparent Oral Clearance (CL/F)	Single dose and multiple dose PK will be calculated as data permits	At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Secondary	Pharmacokinetic Parameters: Apparent Volume of Distribution (Vz/F)	Single dose and multiple dose PK will be calculated as data permits	At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Secondary	Pharmacokinetic Parameters: Plasma Decay Half-Life (t1/2)	Singe dose and multiple dose PK will be calculated as data permits	At specific timepoints from Cycle 1 day 1 to End of Treatment visit
Secondary	Evaluate the impact of PF-06821497 on patient reported outcomes.	Quality of Life and Time to Functional Status Deterioration as assessed by FACT-P.	At specific time-points from Cycle 1 Day 1 to End of Treatment visit.

External Links

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