Phase 1 Study Of Aurora Kinase Inhibitor PF-03814735 In P... | NCT00424632

Phase 1 Study Of Aurora Kinase Inhibitor PF-03814735 In P... | NCT00424632 | Trialant

Arms/Interventions Module

Label	Type	Description	Intervention Names
Single arm dose escalation	Experimental		Drug: PF-03814735

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PF-03814735	Drug	1, 5, and 25 mg gelatin capsules administered orally once a day from day 1 to day 5, or from day 1 to day 10 every 3 weeks until disease progression or unacceptable toxicity.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) Graded According to Common Terminology Criteria Adverse Events (CTCAE), Version 3	DLT defined as any of the following during the first cycle of treatment and attributable to PF-03814735: Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for >7 days or febrile neutropenia (ANC <1000/mm^3, fever ≥38 degrees Celsius; neutropenic infection (ANC <1000/mm^3); Gr 4 thrombocytopenia (platelets <25,000 cells/mm^3); ≥Gr 3 nausea, vomiting, or diarrhea, despite optimal antiemetic, anti-diarrheal support; ≥20% decrease in left ventricular ejection fraction compared to baseline; other non-hematological toxicity; any Gr ≥3 adverse event; or failure to recover.	Day 1 up to Day 21 of first cycle

Secondary Outcomes

Measure	Description	Time Frame
Maximum Observed Serum Concentration (Cmax)		Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose
Time for Maximum Observed Serum Concentration (Tmax)		Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

Contacts/Locations Module

Name	Affiliation	Role
Pfizer CT.gov Call Center	Pfizer	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Pfizer Investigational Site		Nashville	Tennessee	37203	United States
Pfizer Investigational Site

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
21852114	Derived	Schoffski P, Jones SF, Dumez H, Infante JR, Van Mieghem E, Fowst C, Gerletti P, Xu H, Jakubczak JL, English PA, Pierce KJ, Burris HA. Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours. Eur J Cancer. 2011 Oct;47(15):2256-64. doi: 10.1016/j.ejca.2011.07.008. Epub 2011 Aug 16.

Label	URL
To obtain contact information for a study center near you, click here.	View source

Arm/Group Information

ID	Title	Description
FG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
FG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
FG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
FG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
FG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
FG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
FG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
FG007	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
FG008	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
FG009	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG0001 subjects FG0011 subjects FG0021 subjects FG0034 subjects FG0043 subjects FG00515 subjects FG0067 subjects FG0073 subjects FG00816 subjects FG0096 subjects
COMPLETED		FG0000 subjects FG0010 subjects FG0020 subjects FG0030 subjects FG004
NOT COMPLETED		FG0001 subjects FG0011 subjects FG0021 subjects FG0034 subjects FG004

Type	Comment	Reasons
Death		FG0000 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	PF-03814735 (Schedule A)	Participants received daily dosing of PF-03814735 of 5, 10, 20, 40, 60, 80, or 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
BG001	PF-03814735 (Schedule B)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants With First Cycle Dose Limiting Toxicities (DLTs) Graded According to Common Terminology Criteria Adverse Events (CTCAE), Version 3

DLT defined as any of the following during the first cycle of treatment and attributable to PF-03814735: Grade (Gr) 4 neutropenia (absolute neutrophil count [ANC] <500 cells/mm^3) for >7 days or febrile neutropenia (ANC <1000/mm^3, fever ≥38 degrees Celsius; neutropenic infection (ANC <1000/mm^3); Gr 4 thrombocytopenia (platelets <25,000 cells/mm^3); ≥Gr 3 nausea, vomiting, or diarrhea, despite optimal antiemetic, anti-diarrheal support; ≥20% decrease in left ventricular ejection fraction compared to baseline; other non-hematological toxicity; any Gr ≥3 adverse event; or failure to recover.

Safety population: Same as the As-treated population, defined as all patients enrolled in the study that received at least 1 dose of the study medication.

Posted

Number

participants

Day 1 up to Day 21 of first cycle

ID	Title	Description
OG000

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (12.1)	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA (12.1)	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Pfizer ClinicalTrials.gov Call Center	Pfizer, Inc.	1-800-718-1021		ClinicalTrials.govCallCenter@pfizer.com

Intervention Browse Module

ID	Term
C550549	N-(2-(6-(4-cyclobutylamino-5-trifluoromethylpyrimidine-2-ylamino)-1,2,3,4-tetrahydro-1,4-epiazano-naphthalen-9-yl)-2-oxo-ethyl)acetamide

Secondary

Maximum Observed Serum Concentration (Cmax)

Pharmacokinetic (PK) parameter analysis set: Enrolled participants who received at least 1 dose of study treatment who had at least 1 of the PK parameters of interest estimated in at least 1 treatment period.

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 25 mg (Schedule B)	Participant was randomized to receive daily dosing of PF-03814735 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.
OG008	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG010	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0001 OG0011 OG0021 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.1920± NAGeometric coefficient of variation (CV) % was not calculated for treatment groups with N \<3., OG0010.6470± NAGeometric CV % was not calculated for treatment groups with N \<3. OG002

Secondary

Time for Maximum Observed Serum Concentration (Tmax)

PK parameter analysis set

Posted

Median

Full Range

hours

Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 25 mg (Schedule B)	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.
OG008	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG010	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0001 OG0011 OG0021 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002.00± NA(2.00 to 2.00) OG0011.00± NA(1.00 to 1.00) OG00224.0± NA(24.0 to 24.0)

Secondary

Area Under the Serum Concentration Time Profile From Time Zero to the Time of the Last Quantifiable Concentration (AUClast)

Area under the serum concentration time-curve from zero to the last measured concentration.

Data was not summarized as the development of the compound was discontinued.

Posted

Median

Full Range

mcg*hr/mL

Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 25 mg (Schedule B)	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.
OG008	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG010	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Area Under the Serum Concentration Time Profile From Time 0 to Time Tau (τ), the Dosing Interval, Where τ = 24 Hours (AUCτ).

PK parameter analysis set

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg*hr/mL

Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 25 mg (Schedule B)	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.
OG008	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG010	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0001 OG0011 OG0021 OG003

Title

Denominators

Categories

Title	Measurements
	OG0002.957± NAGeometric CV % was not calculated for treatment groups with N \<3. OG00110.09± NAGeometric CV % was not calculated for treatment groups with N \<3. OG002

Secondary

Minimum Observed Serum Trough Concentration (Cmin)

Cmin defined as the lowest serum concentration observed during the dosing interval.

PK parameter analysis set

Posted

Geometric Mean

Geometric Coefficient of Variation

mcg/mL

Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 25 mg (Schedule B)	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.
OG008	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG010	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0001 OG0011 OG0021 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000.05440± NAGeometric CV % was not calculated for treatment groups with N \<3. OG0010.2330± NAGeometric CV % was not calculated for treatment groups with N \<3. OG002

Secondary

Observed Serum Accumulation Ratio (Rac)

Rac was the ratio of Schedule B Cycle 1/Day 9 to Day -5 (Day 9 AUCτ to Day -5 AUCτ).

PK parameter analysis set. N=number of participants in the indicated population contributing to the mean.

Posted

Geometric Mean

Geometric Coefficient of Variation

ratio

Schedule B Day-5: pre-dose, 0.5, 1, 2, 4, 6, 10, 24, 32, 48, and 72 hours post-dose, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0003 OG00113 OG0026

Title

Denominators

Categories

Title	Measurements
	OG0001.054± 28 OG0011.503± 44 OG0021.247± 27

Secondary

Terminal Half-life (t 1/2)

Terminal half-life (serum decay half-life) is the time measured for the serum concentration to decrease by one half.

Half-life (t ½) was not reported for multiple-dose data since the 24-hour sampling period was not long enough to adequately characterize t ½.

Posted

Mean

Standard Deviation

hours

Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 25 mg (Schedule B)	Participant was randomized to receive daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis. However, participant had reduced dose of 25 mg beginning on Cycle 1 Day 1 of treatment.
OG008	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG010	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Urine Pharmacokinetics

Urine PK for quantification of unchanged PF-03814375 and any identified metabolites. 24-hour urine collection at 8-hour intervals after the morning dose (Schedule [Sch] A Day 4, Sch B Day 9; last sample collected just prior to the morning dose on Sch A Day 5 or Sch B Day 10 in the expanded maximum tolerated dose (MTD) cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups). The lower limit of quantification (LLOQ) was 1 nanogram per milliliter (ng/mL). Clinical specimens with concentrations below the LLOQ were to be reported as below the limited of quantification (BLQ) 1 ng/mL.

Data was not summarized as the development of the compound was discontinued.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Schedule A Cycle 1/Day 4, Schedule B Cycle 1/Day 9: pre-dose, 0.5, 1, 2, 4, 6, 10, and 24 hours post-dose

ID	Title	Description
OG000	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010

Secondary

Summary of Tumor Metabolism Assessed by Positron Emission Tomography With F-18-fluorodeoxyglucose (FDG-PET)

FTD-PET measured as standardized uptake volume (SUV) values corrected for lean body mass. Change from baseline categorized according to European Organization for Research and Treatment for Cancer (EORTC) criteria: Partial Metabolic Response (PMR): SUV value during treatment <75 percent (%) of baseline value; Progressive Metabolic Disease (PMD): SUV value during treatment >125% of baseline value; Stable Metabolic Disease (SMD): change in SUV value between PMR and PMD. Collected in the expanded MTD cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups).

Data was not summarized as the development of the compound was discontinued.

Posted

Mean

Standard Deviation

percent change

Baseline (Schedule A or Schedule B Day -7) and Schedule A Cycle 1/Day 3 or Day 4, Schedule B Cycle 1/Day 8 or 9

ID	Title	Description
OG000	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010

Secondary

Target Modulation by Phosphohistone H3 (pH3) Expression in Tumor Tissue (IHC)

pH3 expression is a method to enable the quantification of the proliferative potential of tumor cells. Post-dose tumor tissue sampling occurred after FDG-PET. Biopsies were not to be taken from lesions which were used for PET analysis and were to be taken between 1 and 6 hours after study drug administration. Collected in the expanded MTD cohort only (≥ 10 participants in Sch A 80 mg and Sch B 50 mg groups).

Data was not summarized as the development of the compound was discontinued.

Posted

Mean

Standard Deviation

percentage of cells

Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10

ID	Title	Description
OG000	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010

Secondary

Number of Participants With Objective Tumor Response

Number of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Data was not summarized as the development of the compound was discontinued.

Posted

Number

participants

Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG008	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Time to Progression

Time to Progression defined as the time from the date of enrollment to the date progressive disease first reported. If tumor progression data included more than 1 date, the first date was to be used. TTP = (first date of tumor progression - date of enrollment + 1). Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since treatment start or appearance of ≥1 new lesions.

Data was not summarized as the development of the compound was discontinued.

Posted

Number

months

Baseline, every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG008	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Duration of Response

Duration of responses based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to RECIST. Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.

Data was not summarized as the development of the compound was discontinued.

Posted

Number

months

Every 2 cycles (each cycle=21 days) until disease progression or participant discontinuation; maximum follow-up was from baseline up to 12 cycles

ID	Title	Description
OG000	PF-03814735 5 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 5 milligrams (mg) administered orally (PO) every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 10 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 10 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG002	PF-03814735 20 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 20 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG003	PF-03814735 40 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG004	PF-03814735 60 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG005	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG006	PF-03814735 100 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 100 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG007	PF-03814735 40 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 40 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG008	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.
OG009	PF-03814735 60 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 60 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010 OG0020 OG003

Secondary

Germ Line Polymorphism of Candidate Genes Targeted by PF-03814735

Percentage of germ line polymorphism cell expression in relation to clinical response. Responses include CR: disappearance of all target lesions; PR: ≥30% decrease in sum of LD of target lesions referencing baseline sum LD; Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions; Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start.

Data was not summarized as the development of the compound was discontinued.

Posted

Number

percentage of cells

Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)

ID	Title	Description
OG000	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010

Secondary

Aurora Gene Somatic Mutations/Amplification and Pathway Genes in Tumor Tissue

Percentage of aurora gene somatic mutations/amplification and pathway genes in relation to clinical response. Responses include CR: disappearance of all target lesions; PR: ≥30% decrease in sum of longest dimensions (LD) of target lesions referencing baseline sum LD; Progressive disease: ≥20% increase in sum LD of target lesions from smallest sum LD recorded since Tx start or appearance of ≥1 new lesions; Stable disease: neither sufficient shrinkage to=PR nor sufficient increase to=PD during first 6 weeks after Tx start referencing smallest sum LD since Tx start.

Data was not summarized as the development of the compound was discontinued.

Posted

Number

percentage of cells

Schedule A Cycle 1 or Cycle 2 /Day 4 or Day 5, Schedule B Cycle 1/Day 9 or Day 10 (each cycle=21 days)

ID	Title	Description
OG000	PF-03814735 80 mg (Schedule A)	Participants received daily dosing of PF-03814735 of 80 mg administered PO every morning on an empty stomach for 5 consecutive days out of 21-day cycles on an outpatient basis.
OG001	PF-03814735 50 mg (Schedule B)	Participants received daily dosing of PF-03814735 of 50 mg administered PO every morning on an empty stomach for 10 consecutive days out of 21-day cycles on an outpatient basis.

Units	Counts
Participants	OG0000 OG0010