Asian Phase I Study Of PF-03446962

Neoplasms Clinical Trial

Official title:

A Phase I Pharmacokinetic And Pharmacodynamic Study Of Pf-03446962 In Asian Patient With Advanced Solid Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01337050
• Other study ID #: A8471004
• Status: Completed
• Phase: Phase 1
• First received: April 6, 2011
• Last updated: October 6, 2015
• Start date: July 2011
• Est. completion date: March 2014

Study information

• Verified date: October 2015
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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].

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: March 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• PF-03446962
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.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital East	Kashiwa	Chiba
Korea, Republic of	Seoul National University Hospital/Department of Internal Medicine	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

Japan,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD)	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.	Baseline up to Week 6	Yes
Primary	Recommended Phase-2 Dose (RP2D)	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.	Baseline up to 28 days after last dose of study medication	Yes
Secondary	Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)	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).	Baseline up to 28 days after last dose	Yes
Secondary	Number of Participants With Treatment Emergent Adverse Events (AEs) Based on Severity	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).	Baseline up to 28 days after last dose	Yes
Secondary	Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)	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.	Baseline up to 28 days after last dose	Yes
Secondary	Number of Participants With Laboratory Abnormalities	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.	Baseline up to 28 days after last dose	Yes
Secondary	Maximum Observed Serum Concentration (Cmax)		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	No
Secondary	Minimum Observed Serum Trough Concentration (Cmin)		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	No
Secondary	Time to Reach Maximum Observed Plasma Concentration (Tmax)		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	No
Secondary	Area Under the Curve From Time Zero to 28 Days [AUC (0-28)]	AUC (0-28)= Area under the plasma concentration versus time curve from time zero (pre-dose) to time of last quantifiable concentration (0-28).	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	No
Secondary	Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast)	Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) for drug.	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	No
Secondary	Systemic Clearance (CL)	CL is a quantitative measure of the rate at which a drug substance is removed from the body.	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	No
Secondary	Volume of Distribution (Vd)	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.	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	No
Secondary	Plasma Decay Half-Life (t1/2)	Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.	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	No
Secondary	Soluble Proteins Level	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.	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)	No
Secondary	Number of Participants With Human Anti-Human Antibody (HAHA)	HAHA analysis was performed using validated, sensitive and specific chemiluminescence enzyme-linked immunosorbent assay (ELISA) methodology.	Baseline, Post-dose (Day 1 of every Cycle up to 28 days after last dose) up to Cycle 30	No
Secondary	Number of Participants With Best Overall Response (BOR)	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.	Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)	No
Secondary	Number of Participants With Clinical Benefit Response (CBR)	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.	Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)	No
Secondary	Progression Free Survival (PFS)	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.	Baseline, thereafter every 6 weeks up to end of treatment (up to Cycle 30)	Yes

External Links

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