Clinical trial NCT01286467: A Study Of PF-04449913 Administered Alone In Select Solid Tumors
Official title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF PF 04449913, AN ORAL HEDGEHOG INHIBITOR, ADMINISTERED AS SINGLE AGENT IN SELECT SOLID TUMORS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Solid Tumors
Keywords: PF-04449913
Hedgehog Inhibitor
Solid tumor
Pharmacokinetics
Safety
Pharmacodynamics
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-01-31
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study examines the effect of a small molecule inhibitor to the Sonic Hedgehog pathway on select solid tumors.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological diagnosis of advanced/metastatic solid tumor
* Adequate Bone Marrow Function
* Adequate Renal Function
* Adequate Liver Function

Exclusion Criteria:

* Patients with known symptomatic brain metastases requiring steroids
* Current active treatment on another clinical trial
* Major surgery or radiation therapy within 4-weeks of starting study treatment

Primary outcomes:
measure: Number of Participants With First Cycle Dose Limiting Toxicities (DLTs)
timeFrame: Baseline up to end of Cycle 1 (Study Day 28)
Secondary outcomes:
measure: Percentage of Participants With Treatment-emergent Adverse Events (AEs), by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (Version 4.0) Grade
timeFrame: Baseline up to 28 days post last dose of study medication (maximum duration: 14 cycles [each cycle of 28 days])
measure: Percentage of Participants With Treatment-related AEs, by NCI CTCAE (Version 4.0) Grade
timeFrame: Baseline up to 28 days post last dose of study medication (maximum duration: 14 cycles [each cycle of 28 days])
measure: Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression (Ratio) to Baseline for Normal Skin on Cycle 1/Day 15
timeFrame: Baseline and Cycle 1/Day 15
measure: Maximum Observed Plasma Concentration (Cmax) on Cycle 1/Day 1
timeFrame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1
measure: Maximum Observed Plasma Concentration (Cmax) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1/Day 1
timeFrame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1/Day 1
timeFrame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1
measure: Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Plasma Decay Half-life (t1/2) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Apparent Oral Clearance (CL/F) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Apparent Volume of Distribution (Vz/F) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Accumulation Ratio (Rac) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 6, 10 and 24 hours post dose on Cycle 1/Day 1, and pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Average Concentration at Steady State (Cavg) on Cycle 1/Day 25
timeFrame: Pre dose, 1, 2, 4, 10, 24, 48, 72 and 96 hours post dose on Cycle 1/Day 25
measure: Number of Participants With Increase From Baseline in Corrected QT Using Fridericia's Formula (QTcF) Interval
timeFrame: Baseline up to Cycle 14 (each cycle 28 days)
measure: Number of Participants With Decrease From Baseline in QTcF Interval
timeFrame: Baseline up to Cycle 14 (each cycle 28 days)
measure: Number of Participants With Post-baseline QTcF Interval Greater Than or Equal to 500 Msec
timeFrame: Baseline up to Cycle 14 (each cycle 28 days)
measure: Percentage of Participants With Objective Response
timeFrame: Baseline up to Cycle 14 (each cycle 28 days)
measure: Progression-Free Survival (PFS)
timeFrame: Baseline up to Cycle 14 (each cycle 28 days)
measure: Time to Progression (TTP)
timeFrame: Baseline up to Cycle 14 (each cycle 28 days)
measure: Duration of Response (DR)
timeFrame: Baseline up to Cycle 14 (each cycle 28 days)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Keck Hospital of University of Southern California
state: California
city: Los Angeles
country: United States
facility: Los Angeles County-University of Southern California Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California/Norris Comprehensive Cancer Center/Investigational Drug Service
state: California
city: Los Angeles
country: United States
facility: University of Southern California/Norris Comprehensive Cancer Center
state: California
city: Aurora
country: United States
facility: Anschutz Cancer Pavilion
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Hospital
state: Colorado
city: Boston
country: United States
facility: Brigham and Women's Hospital (BWH)
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute (DFCI)
state: Massachusetts
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Fostvedt LK, Shaik N, Martinelli G, Wagner AJ, Ruiz-Garcia A. Exposure-response modeling of the effect of glasdegib on cardiac repolarization in patients with cancer. Expert Rev Clin Pharmacol. 2021 Jul;14(7):927-935. doi: 10.1080/17512433.2021.1925538. Epub 2021 May 18.
citation: Wagner AJ, Messersmith WA, Shaik MN, Li S, Zheng X, McLachlan KR, Cesari R, Courtney R, Levin WJ, El-Khoueiry AB. A phase I study of PF-04449913, an oral hedgehog inhibitor, in patients with advanced solid tumors. Clin Cancer Res. 2015 Mar 1;21(5):1044-51. doi: 10.1158/1078-0432.CCR-14-1116. Epub 2014 Nov 11.