Clinical trial NCT03854227: A Dose Escalation Study Of PF-06939999 In Participants With Advanced Or Metastatic Solid Tumors
Official title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF ESCALATING DOSES OF PF-06939999 (PRMT5 INHIBITOR) IN PARTICIPANTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER, HEAD AND NECK SQUAMOUS CELL CARCINOMA, ESOPHAGEAL CANCER, ENDOMETRIAL CANCER, CERVICAL CANCER AND BLADDER CANCER
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Metastatic Solid Tumors
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2019-02-26
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Dose Escalation and Dose expansion
Primary purpose: TREATMENT

Brief summary: This is a Phase 1, open label, multi center, dose escalation and expansion, safety, tolerability, PK, and pharmacodynamics study of PF 06939999 in previously treated patients with advanced or metastatic cancer.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed locally advanced or metastatic NSCLC, urothelial carcinoma or HNSCC
* Progressed after at least 1 line of treatment and no more than 3 lines of treatment
* At least one measurable lesion as defined by RECIST version 1.1
* ECOG Performance Status 0 or 1
* Adequate Bone Marrow Function
* Adequate Renal Function
* Adequate Liver Function
* Resolved acute effects of any prior therapy

Exclusion Criteria:

* Known active uncontrolled or symptomatic CNS metastases.
* Major surgery, radiation therapy, systemic anti-cancer therapy or investigational drug(s) within 4 weeks prior to study entry.
* Active, uncontrolled infection, including COVID-19
* Known or suspected hypersensitivity to PF-06939999
* Inability to consume or absorb study drug

Primary outcomes:
measure: Part 1A: Number of Participants With Dose-Limiting Toxicities (DLT)
timeFrame: Baseline through day 29.
measure: Part 1A: Number of Participants With Treatment-Emergent Adverse Events (TEAE)
timeFrame: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 13 months)
measure: Part 1A: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 12 months)
measure: Part 2: Number of Participants With TEAEs
timeFrame: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 15 months)
measure: Part 2: Number of Participants With Laboratory Abnormalities
timeFrame: Baseline up to a minimum of 28 days after last dose of study treatment (maximum of 8 months)
measure: Part 2: Number of Participants With Best Overall Response (BOR) Based on Investigator Assessment (RECIST, Version 1.1)
timeFrame: From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months).
Secondary outcomes:
measure: Part 1A: PK Parameters of PF-06939999: Single Dose (SD) - Maximum Observed Plasma Concentration (Cmax)
timeFrame: Pre-dose and 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 12 hours post the morning dose on Cycle 1 Day 1.
measure: Part 1A: PK Parameters of PF-06939999: SD - Time to Reach Maximum Observed Plasma Concentration (Tmax)
timeFrame: Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 1.
measure: Part 1A: PK Parameters of PF-06939999: SD - Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
timeFrame: Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 1.
measure: Part 1A: PK Parameters of PF-06939999: Multiple Dose (MD) - Steady State Maximum Observed Plasma Concentration (Cmax,ss)
timeFrame: Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15.
measure: Part 1A: PK Parameters of PF-06939999: MD - Steady State Time to Reach Maximum Observed Plasma Concentration (Tmax,ss)
timeFrame: Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15.
measure: Part 1A: PK Parameters of PF-06939999: MD - Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau,ss)
timeFrame: Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15.
measure: Part 1A: PK Parameters of PF-06939999: MD - Apparent Oral Clearance (CL/F)
timeFrame: Predose, 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15.
measure: Part 1A: PK Parameters of PF-06939999: MD - Accumulation Ratio (Rac)
timeFrame: Pre-dose and 0.5 hour, 1 hour, 2 hours, 4 hours, 6 hours and 12 hours post the morning dose on Cycle 1 Day 1; Pre-dose and 0.5, 1, 2, 4, 6 and 12 hours post the morning dose on Cycle 1 Day 15.
measure: Part 2: PK Parameters of PF-06939999: SD - Cmax
timeFrame: Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 1 dosing.
measure: Part 2: PK Parameters of PF-06939999: SD - Tmax
timeFrame: Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 1 dosing.
measure: Part 2: PK Parameters of PF-06939999: MD - Cmax,ss
timeFrame: Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 15 dosing.
measure: Part 2: PK Parameters of PF-06939999: MD - Tmax,ss
timeFrame: Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 15 dosing.
measure: Part 2: PK Parameters of PF-06939999: MD - Trough Concentration (Ctrough).
timeFrame: Pre-dose and 0.5 hour, 1 hour, 2 hours and 4 hours post Cycle 1 Day 15 dosing.
measure: Part 2B: PK Parameters of PF-06939999 Given With and Without Food - Cmax
timeFrame: Predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 15 (fasted condition); predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 16 (with food).
measure: Part 2B: PK Parameters of PF-06939999 Given With and Without Food - Tmax
timeFrame: Predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 15 (fasted condition); predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 16 (with food).
measure: Part 2B: PK Parameters of PF-06939999 Given With and Without Food - AUClast
timeFrame: Predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 15 (fasted condition); predose and 0.5, 1, 2, 4, 6 and 12 hours post dose on Cycle 1 Day 16 (with food).
measure: Part 1A: Percentage of Participants With Objective Response Based on Investigator Assessment (RECIST v1.1)
timeFrame: From baseline up to 28 ~ 35 days after end of treatment (maximum of 12 months).
measure: Part 1A: Duration of Response Based on Investigator Assessment (RECIST, v1.1)
timeFrame: From baseline up to 28 ~ 35 days after end of treatment (maximum of 12 months).
measure: Part 2: Duration of Response Based on Investigator Assessment (RECIST, v1.1)
timeFrame: From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months).
measure: Part 2: Progression Free Survival Based on Investigator Assessment (RECIST, v1.1)
timeFrame: From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months).
measure: Part 2: Time to Progression Based on Investigator Assessment (RECIST, v1.1)
timeFrame: From baseline up to 28 ~ 35 days after end of treatment (maximum of 6 months).
measure: Part 2: Overall Survival
timeFrame: From baseline up to maximum follow up (15 months).
measure: Part 2: Probability of Survival at 6 Months and 1 Year of PF-06939999 Monotherapy
timeFrame: From baseline up to maximum follow up (15 months).
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Scottsdale Healthcare Hospitals d/b/a HonorHealth
state: Arizona
city: Scottsdale
country: United States
facility: Virginia G. Piper Cancer Pharmacy
state: Arizona
city: Los Angeles
country: United States
facility: Keck Hospital of USC
state: California
city: Los Angeles
country: United States
facility: LAC + USC Medical Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center
state: California
city: Pasadena
country: United States
facility: Keck Medical Center of USC Pasadena
state: California
city: Celebration
country: United States
facility: AdventHealth Celebration Infusion Center
state: Florida
city: Celebration
country: United States
facility: AdventHealth Medical Group Oncology Research at Celebration
state: Florida
city: Miami
country: United States
facility: University Of Miami Hospital and Clinics/Sylvester Comprehensive Cancer Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando - Investigational Drug Services
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando Infusion Center
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando
state: Florida
city: Ann Arbor
country: United States
facility: St. Joseph Mercy Hospital
state: Michigan
city: Brighton
country: United States
facility: St. Joseph Mercy Brighton
state: Michigan
city: Nashville
country: United States
facility: Henry-Joyce Cancer Clinic
state: Tennessee
city: Nashville
country: United States
facility: Oncology IDS Pharmacy
state: Tennessee
city: Houston
country: United States
facility: The University of Texas
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: Fairfax
country: United States
facility: Inova Schar Cancer Institute
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Seattle
country: United States
facility: University of Washington Medical Center
state: Washington
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: