- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01337050
Asian Phase I Study Of PF-03446962
October 6, 2015 updated by: Pfizer
A Phase I Pharmacokinetic And Pharmacodynamic Study Of Pf-03446962 In Asian Patient With Advanced Solid Tumors
This is an Asian Phase 1, multi center, open label, single arm study of PF 03446962 with dose escalation and designed to define the Maximum Tolerated Dose [MTD] and the Recommended Phase 2 Dose [RP2D].
Study Overview
Study Type
Interventional
Enrollment (Actual)
36
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Chiba
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Kashiwa, Chiba, Japan, 277-8577
- National Cancer Center Hospital East
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Seoul, Korea, Republic of, 110-744
- Seoul National University Hospital/Department of Internal Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Confirmed diagnosis of stomach cancer
- advanced/metastasis solid tumor refractory or intolerant to established therapy
- adequate blood chemistry, blood counts and kidney/liver function
- willing to participate to study requirements and sign an informed consent document
Exclusion Criteria:
- Chemotherapy, radiotherapy, or any investigational cancer therapy within 4 weeks of first dose of study medication
- excessive toxicities related to prior therapies
- pregnant or breastfeeding patients
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: A
PF-03446962
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PF 03446962 given by a 1 hour IV infusion.
Each patient will initially receive the first dose on Cycle 1 Day 1 with a 28 day observation period.
Cycle 2 will start on Day 29.
The dosing interval will be 14 days for Cycle 2 and subsequent cycles.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum Tolerated Dose (MTD)
Time Frame: Baseline up to Week 6
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The MTD was defined as the highest dose of PF-03446962 associated with the occurrence of Dose Limiting Toxicities (DLTs) in at most 1 of 6 participants with the next higher dose having at least 2/3 or 2/6 participants experiencing DLTs (that is (i.e.) Maximum Administrated Dose).
DLT is defined if the participants meets the following criteria during the first 6 weeks of treatment, possibly attributable to PF-03446962.
Neutropenia grade 4 (less than [< ])500/cubic millimeter [mm^ 3]) lasting for greater than equal to (>=) 8 days; Febrile Neutropenia >= Grade 3; Neutropenic Infection >= Grade 3; Grade 4 thrombocytopenia (<25,000/mm^3); Grade 3 thrombocytopenia (<50,000/mm^3) with active bleeding; Grade 3 or higher non-hematological toxicity.
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Baseline up to Week 6
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Recommended Phase-2 Dose (RP2D)
Time Frame: Baseline up to 28 days after last dose of study medication
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RP2D was determined by a comprehensive assessments based on all the safety data, efficacy data, pharmacokinetics profile and biomarker data using blood and tumor samples.
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Baseline up to 28 days after last dose of study medication
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to 28 days after last dose
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An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Treatment-emergent were events between first dose of study drug and up to 28 days after last dose that were absent before treatment or that worsened relative to pre-treatment state.
AEs included both SAEs and non-serious adverse events (non-SAEs).
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Baseline up to 28 days after last dose
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Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity
Time Frame: Baseline up to 28 days after last dose
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Adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship.
AE was assessed according to severity; Grade 1 (Mild Adverse Event), Grade 2 (Moderate Adverse Event), Grade 3 (Severe Adverse Event), Grade 4 (Life- Threatening or Disabling Adverse Event), Grade 5 (Death Related to Adverse Event).
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Baseline up to 28 days after last dose
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Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to 28 days after last dose
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An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug.
An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
AEs included both SAEs and non-serious adverse events (non-SAEs).
Relatedness to study drug was assessed based on investigator's discretion.
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Baseline up to 28 days after last dose
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Number of Participants With Laboratory Abnormalities
Time Frame: Baseline up to 28 days after last dose
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Laboratory abnormalities were segregated into hematology, chemistry, coagulation and urinalysis test.
It had been graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) into Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (Life-threatening).
Participants with abnormality of any of these grades are reported.
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Baseline up to 28 days after last dose
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Maximum Observed Serum Concentration (Cmax)
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Minimum Observed Serum Trough Concentration (Cmin)
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Area Under the Curve From Time Zero to 28 Days [AUC (0-28)]
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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AUC (0-28)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-28).
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) for drug.
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Systemic Clearance (CL)
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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CL is a quantitative measure of the rate at which a drug substance is removed from the body.
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Volume of Distribution (Vd)
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Plasma Decay Half-Life (t1/2)
Time Frame: 0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
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0 (pre dose), 0.5, 1 (right before the end of infusion), 1.5, 2, 5, 8, 24 hours after the start of infusion of the first dose on Day 1; Day 3, 5, 8, 11, 15, 22 of Cycle 1
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Soluble Proteins Level
Time Frame: Baseline, Day 1, 0 hour (H), 6 H Cycle 1 Day 1, Day 22 of Cycle 1, Day 1 Cycle 2, Day 1 Cycle 3 and end of treatment (up to cycle 30)
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Soluble proteins related to Activin Receptor-Like Kinase 1 (ALK-1) signaling and angiogenesis signaling including Vascular adhesion molecule (VAM), Monocyte chemotactic protein 1 (MCP-1), Angiopoietin 2, Tear intercellular adhesive molecule 1 (ICAM-1), Soluble intracellular adhesion molecule 1 (SIAM-1), Soluble vascular adhesion molecule 1 (SVAM-1), Vascular endothelial growth factor A (VEGF-A), Vascular endothelial growth factor C (VEGF-C), Vascular endothelial growth factor D (VEGF-D), Soluble vascular endothelial growth factor- Receptor 1 (REC 1) (SVEGF-REC 1), Soluble vascular endothelial growth factor- REC 2 (SVEGF-REC 2), Soluble vascular endothelial growth factor- REC 3 (SVEGF-REC 3), Bone morphogenetic protein-9 (BMP-9), Endoglin, Transforming growth factor- beta 1 (TGF- Beta 1), Placental growth factor (PGF) was evaluated.
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Baseline, Day 1, 0 hour (H), 6 H Cycle 1 Day 1, Day 22 of Cycle 1, Day 1 Cycle 2, Day 1 Cycle 3 and end of treatment (up to cycle 30)
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Number of Participants With Human Anti-Human Antibody (HAHA)
Time Frame: Baseline, Post-dose (Day 1 of every Cycle up to 28 days after last dose) up to Cycle 30
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HAHA analysis was performed using validated, sensitive and specific chemiluminescence enzyme-linked immunosorbent assay (ELISA) methodology.
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Baseline, Post-dose (Day 1 of every Cycle up to 28 days after last dose) up to Cycle 30
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Number of Participants With Best Overall Response (BOR)
Time Frame: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)
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Number of participants with best overall response according to Response Evaluation Criteria in Solid Tumors (RECIST); Complete response (CR): disappearance of all lesions, Pathological lymph nodes' reduction in short axis (SA) to less than (<)10 millimeter (mm); Partial response (PR): greater than equal to (>=) 30% decrease in sum of longest dimensions (LD) of Target Lesions (TL) taking reference baseline sum LD; Progressive disease (PD):>=20% (>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of >=1 new lesions, unequivocal progression of existing non-TL, or appearance of >=1 new lesion; Stable disease (SD): insufficient shrinkage to qualify for PR, insufficient increase to qualify for PD taking reference smallest sum of the LD since treatment start.
Confirmed response=that persist at least 4 weeks after initial documentation.
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Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)
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Number of Participants With Clinical Benefit Response (CBR)
Time Frame: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)
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Number of participant with clinical benefit response (CBR): CBR was defined as CR, PR, SD >12 weeks, SD<12weeks or PD according to RECIST criteria; Complete response (CR): disappearance of all lesions, Pathological lymph nodes' reduction in short axis (SA) to <10 mm; Partial response (PR): >=30% decrease in sum of longest dimensions (LD) of Target Lesions (TL) taking reference baseline sum LD; Progressive disease (PD):>=20% (>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of >=1 new lesions, unequivocal progression of existing non-TL, or appearance of >=1 new lesion; Stable disease (SD): insufficient shrinkage to qualify for PR, insufficient increase to qualify for PD taking reference smallest sum of the LD since treatment start.
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Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)
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Progression Free Survival (PFS)
Time Frame: Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)
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PFS was defined as the time from the first dose of study treatment to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first.
PFS calculated as (Months) = (first event date minus randomization or the first dose date plus 1) divided by 30.44).
PFS was calculated using the median, and 95% Confidence Intervals (CIs) and Progressive disease (PD):>=20% (>= 5 mm increase) increase sum of LD of TL taking as a reference smallest sum of LD recorded since treatment start, appearance of >=1 new lesions, unequivocal progression of existing non-TL, or appearance of >=1 new lesion.
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Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
July 1, 2011
Primary Completion (Actual)
December 1, 2013
Study Completion (Actual)
March 1, 2014
Study Registration Dates
First Submitted
April 6, 2011
First Submitted That Met QC Criteria
April 15, 2011
First Posted (Estimate)
April 18, 2011
Study Record Updates
Last Update Posted (Estimate)
October 28, 2015
Last Update Submitted That Met QC Criteria
October 6, 2015
Last Verified
October 1, 2015
More Information
Terms related to this study
Other Study ID Numbers
- A8471004
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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