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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04557449
Other study ID # C4391001
Secondary ID 2020-002938-33
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date September 23, 2020
Est. completion date October 19, 2027

Study information

Verified date December 2023
Source Pfizer
Contact Pfizer CT.gov Call Center
Phone 1-800-718-1021
Email ClinicalTrials.gov_Inquiries@pfizer.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a Phase 1/2A, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of PF-07220060 administered as a single agent and then in combination with endocrine therapy.


Description:

The study consists of two parts and a China and Japan monotherapy cohort. Part 1 includes dose escalation cohorts evaluating PF-07220060 as single agent or in combination with endocrine therapy or enzalutamide, as well as a food effect cohort and a DDI cohort Part 2 includes dose expansion cohorts evaluating PF-07220060 in combination with endocrine therapy or enzalutamide. In Part 1A, single escalating doses of PF-07220060 alone will be administered to determine the maximum tolerated dose (MTD) and select the recommended dose for expansion In Part 1B and Part 1C, PF-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively). In Part 1D, food effect assessment of PF-07220060 at the RP2D dose level from the Part 1A will be conducted In Part 1E, the effect of PF-07220060 on the PK of midazolam will be evaluated (DDI) In Part 1F, escalating dosed of PF-07220060 will be administered in combination with enzalutamide Part 1B and Part 1C may commence at MTD or before reaching the MTD at a dose level in Part 1A. Part 2A is a dose expansion cohort with fulvestrant and will explore more than one dose of PF-07220060 in participants diagnosed with mBC. Part 2B and Part 2C are expansion for combination therapy of PF-07220060 with letrozole and fulvestrant, respectively. Part 2D is the expansion cohort for combination therapy of PF-07220060 with enzalutamide. The China monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as single agent in Chinese participants. The Japan monotherapy cohort will evaluate safety, tolerability and PK of PF-07220060 administered as a single agent in Japanese participants.


Recruitment information / eligibility

Status Recruiting
Enrollment 337
Est. completion date October 19, 2027
Est. primary completion date August 19, 2026
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria - Part 1: Breast Cancer (BC) - Refractory Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-) BC - Part 1A/Part 1D/Part1E also include: Refractory HR-positive/HER2-positive BC - Part 1: Tumors other than BC (Part 1A/Part 1D/Part 1E): NSCLC, prostate, CRC, liposarcoma, or tumors with previously confirmed CDK4 or CCND1 amplification according to local standard tests - Part 1F: prostate cancer - Part 2A, 2B and 2C: - HR-positive/HER2-negative BC - Patients who are either postmenopausal women or pre/peri-menopausal (Part 2C only) - Part 1D: metastatic castration resistant prostate cancer - Lesion: - Part 1: evaluable lesion (including skin or bone lesion only) - Part 2A, 2B and 2C: measurable lesion per RECIST v1.1 - Part 2D: Participants with evaluable disease as per PCWG3; participants with bone metastases only are allowed. Participants with biochemical recurrence only are excluded. - Prior systemic Treatment - Part 1: HR-positive/HER2-negative BC - At least 1 line of SOC, including CD4/6 inhibitor therapy for advanced or metastatic disease, or if CDK4/6 inhibitors are not considered appropriate in the opinion of the investigator - At least 1 line of anti-endocrine in countries without CDK4/6 inhibitor approval or reimbursement, for advanced or metastatic disease - HR-positive/HER2-positive BC (Parts 1A/1D/1E): at least 1 prior treatment of approved HER2 targeting therapy - Tumors other than BC (Parts 1A/1D/1E/1F): tumor that is resistant to at least 2 lines of SOC for advanced or recurrent disease or for which no standard therapy is available - Part 2A: participants must have received at least 1 line of standard of care (including prior CDK4/6i) for advanced/metastatic disease; Prior chemo is allowed; Prior fulvestrant, mTOR and/or PI3K inhibitors are allowed - Part 2B: participants who have not received any prior systemic anti-cancer therapies for advanced/metastatic BC - Part 2C: - Progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or - Progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic BC if postmenopausal or prior endocrine treatment for advanced/metastatic BC if pre or perimenopausal - One previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy - Part 2D: - Received prior abiraterone; enzalutamide and CDK4i naive - 0-1 line of chemotherapy is allowed General Inclusion Criteria - All participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition. - Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1 - Adequate renal, liver, and bone marrow function Exclusion Criteria: - Part 1D: participants who have had a gastrectomy or have dietary or other restrictions that preclude a 10 hour overnight fast or consumption of the high fat, high calorie meal - Part 2B: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. Prior treatment with any CDK4/6 inhibitor - Part 2C: prior treatment with any CDK inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the PI3K-mTOR pathway - Known active uncontrolled or symptomatic Central Nervous System (CNS) metastases carcinomatous meningitis, or leptomeningeal disease - Other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ - Major surgery or radiation within 4 weeks prior to study intervention - Last anti-cancer treatment within 2 weeks prior to study intervention - Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry - Pregnant or breastfeeding female participant - Active inflammatory gastrointestinal (GI) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or GI disease

Study Design


Intervention

Drug:
PF-07220060
CDK4 inhibitor
Combination Product:
Letrozole
Endocrine Therapy
Fulvestrant
Endocrine Therapy
Drug:
Midazolam
Benzodiazepine used for DDI
Combination Product:
Enzalutamide
Androgen Receptor inhibitor

Locations

Country Name City State
Argentina Fundación Respirar Buenos Aires
Argentina Fundación Cenit Para La Investigación En Neurociencias Caba Ciudad Autã³noma DE Buenos Aires
Argentina Hospital Británico de Buenos Aires Ciudad autónoma de Buenos Aires Buenos Aires
Argentina Clínica Universitaria Reina Fabiola Córdoba
Argentina Fundación CORI para la Investigación y Prevención del Cáncer La Rioja
China Cancer Hospital Chinese Academy of Medical Science Beijing Beijing
China Sir Run Run Shaw Hospital, Zhejiang University School of Medicine Hangzhou Zhejiang
China Hubei Cancer Hospital Wuhan Hubei
China The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shaanxi
China The First Affiliated Hospital of Xi'an Jiaotong University Xi'an Shanxi
China Henan Cancer Hospital Zhengzhou Henan
Czechia Fakultni nemocnice Olomouc Olomouc
Czechia Vseobecna fakultni nemocnice v Praze Praha 2
Japan National Cancer Center Hospital East Kashiwa Chiba
Mexico INCAN Cdmx Distrito Federal
Mexico Hospital MAC Periferico Sur Ciudad de Mexico Distrito Federal
Mexico COI Centro Oncologico Internacional S.A.P.I. de C.V. Mexico City Distrito Federal
Mexico Hospital Universitario "Dr. Jose Eleuterio Gonzalez" Monterrey Nuevo LEÓN
Mexico Oaxaca Site Management Organization Oaxaca
Mexico Hospital Reforma Oaxaca de Juárez Oaxaca
Slovakia Narodny onkologicky ustav Bratislava
Slovakia Onkologicky ustav sv. Alzbety, s.r.o., Interna klinika VSZaSP a OUSA Bratislava
Slovakia Fakultna nemocnica s poliklinikou Nove Zamky Nove Zamky
Slovakia POKO Poprad, s.r.o. Poprad
United Kingdom Cancer Research UK Edinburgh Centre Edinburgh Edinburgh, CITY OF
United Kingdom Sarah Cannon Research Institute UK London
United Kingdom St Bartholomew's Hospital London London, CITY OF
United Kingdom The Christie Hospital NHS Foundation Trust Manchester
United States Brigham & Women's Hospital Boston Massachusetts
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Dana-Farber Cancer Institute (DFCI) Boston Massachusetts
United States START Midwest Grand Rapids Michigan
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States Sarah Cannon Research Institute Nashville Tennessee
United States Tennessee Oncology, PLLC Nashville Tennessee
United States Smilow Cancer Hospital at Yale - New Haven New Haven Connecticut
United States Smilow Cancer Hospital Phase 1 Unit New Haven Connecticut
United States Dana Farber Cancer Institute- Chestnut Hill Newton Massachusetts

Sponsors (1)

Lead Sponsor Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Argentina,  China,  Czechia,  Japan,  Mexico,  Slovakia,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of participants with dose limiting toxicities in the Dose Escalation Portion First cycle (28 days) dose limiting toxicities (Parts 1A, 1B, 1C, 1F) Baseline up to day 28 of Cycle 1.
Primary Incidence of clinically significant AEs Adverse Events Weekly during Cycle 1 and 2 and then every 28 days through study completion, up to approximately 24 months; Each cycle is 28 days
Primary Incidence of clinically significant laboratory assessments safety laboratory abnormalities Weekly during Cycle 1 and 2 (each cycle is 28 days) and then every 28 days through study completion, up to approximately 24 months
Primary Incidence of clinically significant abnormal vital and ECG parameters vital signs and heart rate corrected QT interval Day 1, Day 8, Day 15 of Cycle 1 and starting from Cycle 2, and then every 28 days through study completion, up to approximately 24 months (Each cycle is 28 days)
Primary Food Effect Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1D) Day -7 through the end of Cycle 1
Primary DDI Maximal Concentration, Time to Maximum Plasma Concentration, Area under the Plasma Concentration (Part 1E) D1 to the end of Cycle 1
Secondary Single Dose: Maximal concentration (Cmax) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Single Dose: Time to Maximum Plasma Concentration (Tmax) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero to the Last Sampling Time Point Within the Dose Interval (AUClast) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Single Dose: Area Under the Plasma Concentration Versus Time Curve from Time Zero Extrapolated to Infinity (AUCinf) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Time Frame: Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Apparent Oral Plasma Clearance (CL/F) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Single Dose: Apparent Volume of Distribution (Vz/F) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Multiple Dose: Steady State Maximal Concentration (Css,max) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Multiple Dose: Time to Maximum Plasma Concentration at Steady State (Tss,max) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Area Under the Plasma Concentration Versus Time Curve Within One Dose Interval (AUCss,t) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Multiple Dose: Steady State Minimum Plasma Concentration (Css,min) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Multiple Dose: Steady State Apparent Oral Plasma Clearance (CLss/F) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Multiple Dose: Apparent Volume of Distribution at Steady State (Vss/F) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Multiple Dose: Terminal Elimination Half-Life (t1/2) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Multiple Dose: Accumulation Ratio (Rac (AUCss,t /AUCsd,t)) in the Dose Escalation and Dose Finding portion Pharmacokinetic (PK) assessments for PF-07220060 (Parts 1A, 1B, 1C) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Tumor Response per RECIST v1.1 and per PCGW3 Per RECIST v1.1 (Part 1 A-E; Part 2B and 2C); per PCWG3 (Part 1F and Part 2D) baseline up to approximately 24 months
Secondary Duration of Response (DOR) Per RECIST v1.1 baseline up to approximately 24 months
Secondary Progression Free Survival (PFS) PFS per RECIST v.1.1 baseline up to approximately 24 months
Secondary Time to Progression (TTP) TTP per RECIST v1.1 baseline up to approximately 24 months
Secondary Clinical Benefit Rate (CBR) CBR per RECIST v1.1 (Parts 2B, 2C) baseline up to approximately 24 months
Secondary Peak and Trough Concentration of PF-07220060 Peak and trough concentration (Parts 2B, 2C, 2D) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Peak and trough concentrations of enzalutamide and N-desmethyl enzalutamide Peak and trough concentrations (Part 2D) Cycle 1 (each cycle is 28 days) and Day 1 of each subsequent cycle and at study completion visit, up to approximately 24 months
Secondary Time to first skeletal events Time to first skeletal events (Part 2D) Cycle 1 (each cycle is 28 days) to up to approximately 24 months
Secondary Quality of life questionnaire time to functional status deterioration by FACT-P (Part 2D) Cycle 1 (each cycle is 28 days) to up to approximately 24 months
Secondary Radiographic Progression Free survival Part 2D Cycle 1 (each cycle is 28 days) up to approximately 24 months
Secondary PSA50 Part 1F and 2D Cycle 1 (each cycle is 28 days) to up to approximately 24 months
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