A Study Of PF-05212384 Plus FOLFIRI Versus Bevacizumab Pl... | NCT01937715

ID	Type	Description	Link
2013-002096-18	EudraCT Number

Label	Type	Description	Intervention Names
Arm A	Experimental	PF-05212384 plus FOLFIRI	Drug: PF-05212384 Drug: FOLFIRI regimen
Arm B	Active Comparator	Bevacizumab plus FOLFIRI	Biological: Bevacizumab Drug: FOLFIRI

Name	Type	Description	Arm Group Labels	Other Names
PF-05212384	Drug	PF-05212384 at the Recommended phase 2 dose (RP2D/MTD) weekly	Arm A

Measure	Description	Time Frame
Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy	DLTs were classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and defined as any of the following events judged to be attributed to the combination of PF-05212384 plus FOLFIRI: hematologic (febrile neutropenia or a sustained temperature >=38 degrees Celcius for >1 hour, grade >=3 neutropenic infection, grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia); non-hematologic (grade >=2 pneumonitis, grade >=3 toxicities, toxicities which resulted in failure to deliver at least 75% of the planned total dose of PF-05212384 and/or 50% of the planned total dose of FOLFIRI during the first cycle, toxicities which resulted in delay of start of Cycle 2 by >2 weeks of scheduled day (Day 43 of study), Grade 3 QTc prolongation).	Day 1 up to Day 28
Progression-Free Survival (PFS)	Progression-free survival was the time from randomization the date to date of first documentation of progression or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.	Baseline (Day 1) up to disease progression or death whichever occurred first (up to 18 months)

Measure	Description	Time Frame
Number of Participants With Best Overall Response (Phase 1B)	Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented).

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

Facility	Status	City	State	ZIP	Country	Contacts
St. Jude Hospital Yorba Linda DBA St. Joseph Heritage Healthcare		Fullerton	California	92835	United States

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

ID	Title	Description
FG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
FG001

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

Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy

DLTs were classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and defined as any of the following events judged to be attributed to the combination of PF-05212384 plus FOLFIRI: hematologic (febrile neutropenia or a sustained temperature >=38 degrees Celcius for >1 hour, grade >=3 neutropenic infection, grade 3 thrombocytopenia with bleeding, grade 4 thrombocytopenia); non-hematologic (grade >=2 pneumonitis, grade >=3 toxicities, toxicities which resulted in failure to deliver at least 75% of the planned total dose of PF-05212384 and/or 50% of the planned total dose of FOLFIRI during the first cycle, toxicities which resulted in delay of start of Cycle 2 by >2 weeks of scheduled day (Day 43 of study), Grade 3 QTc prolongation).

The dose limiting toxicity analysis set included participants in Phase 1B who started treatment and who did not have a major treatment deviation in the lead-in period and the first cycle of treatment.

Posted

Number

percentage of participants

Day 1 up to Day 28

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG003	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3	Participants received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG004	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4	Participants received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Units	Counts
Participants	OG0003 OG0014 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Primary

Progression-Free Survival (PFS)

Progression-free survival was the time from randomization the date to date of first documentation of progression or death due to any cause, whichever occurred first. Documentation of progression was by objective disease assessment as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

PFS was the primary efficacy endpoint for the study and was only to be assessed in the Phase 2 portion of the study. As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2.

Posted

Baseline (Day 1) up to disease progression or death whichever occurred first (up to 18 months)

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002

Secondary

Number of Participants With Best Overall Response (Phase 1B)

Best overall response is defined as the best response recorded from randomization (or first dose for patients in the Phase 1B) until disease progression, death, start of new anti-cancer treatment or end of study. The categories for best overall response include: complete response (CR) (complete disappearance of all target lesions with the exception of nodal disease and all target nodes must decrease to normal size (short axis <10 millimeters (mm)); partial response (PR) (at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters); stable disease (SD) (not qualify for CR, PR or Progression); progressive disease (PD) (20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy), with a minimum absolute increase of 5 mm); indeterminate (IND) (progression has not been documented).

All participants in the full analysis (FA) set who had measureable disease and an adequate baseline assessment of the disease.

Posted

Number

participants

Every 8 weeks from Cycle 1 Day 1 until 28 days of last dose

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001

Secondary

Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness

An AE was any untoward medical occurrence without regard to causality 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. An AE was considered treatment emergent if the event occurred for the first time after the start of study treatment and within 28 days after final dose of study treatment and was not seen prior to the start of treatment; or the event was seen prior to the start of treatment but increased in CTCAE version 4.0 grade after the start of study treatment and within 28 days after final dose of study treatment.

All participants who received at least 1 dose of study medication.

Posted

Number

participants

Baseline up to final study evaluation (within 28 days of last dose)

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A

Secondary

Number of Participants With All Causality AEs by System Organ Class (SOC)

An AE was any untoward medical occurrence without regard to causality in a participant who received study drug.

All participants who received at least 1 dose of study medication.

Posted

Number

participants

Baseline up to final study evaluation (within 28 days of last dose)

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade

An AE was any untoward medical occurrence without regard to causality in a participant who received study drug. AE grades were defined according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria.

All participants who received at least 1 dose of study medication.

Posted

Number

participants

Baseline up to final study evaluation (within 28 days of last dose)

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Hematological Test Abnormalities

Number of participants with NCI CTCAE version 4.0 grade 1 to 4 hematological test abnormalities.

All participants who received at least 1 dose of study medication.

Posted

Number

participants

Day 1 and Day 15 of each cycle

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Coagulation Test Abnormalities

Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Coagulation test abnormalities.

All participants who received at least 1 dose of study medication. n=number of participants evaluated against criteria.

Posted

Number

participants

Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Chemistry Test Abnormalities

Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Chemistry test abnormalities.

All participants who received at least 1 dose of study medication. n=number of participants evaluated against criteria.

Posted

Number

participants

Day 1 and Day 15 of each cycle

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Urinalysis Test Abnormalities

Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Urinalysis test abnormalities.

All participants who received at least 1 dose of study medication.

Posted

Number

participants

Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cycles

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil

Maximum Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil

Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanogram (ng)/milliliter (mL)

PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B

Secondary

Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil

Time to Reach Maximum Observed Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil

Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.

Posted

Median

Full Range

hour (hr)

PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan

Area Under the Curve From Time Zero to Last Quantifiable Concentration of PF-05212384, and Irinotecan

Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B

Secondary

Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan

Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time of PF-05212384 and Irinotecan

Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B

Secondary

Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan

Terminal Elimination Half-Life of PF-05212384 and Irinotecan

Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.

Posted

Mean

Standard Deviation

hour

PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants Meeting Maximum Post-Baseline QTc Interval Values

Criteria for corrected QT interval using Fridericia's formula (QTcF) meeting potential clinical concern included: an absolute value >=450 - <480 msec, >=480-<500 msec, >500 msec; an absolute change 30 - <60, >=60 msec.

All participants who received at least 1 dose of study medication.

Posted

Number

participants

Baseline, Cycle 1 Day 1, and Cycle 2 Day 2

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Expression of Gene Sequences or Gene Amplications in Biopsied Tumor Tissue

Biomarker evaluation were to be performed on fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.

Paired fresh tumor biopsies were only done in 1 subject but not summarized.

Posted

Baseline and Cycle 2 Day 17

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Gene and/or Protein Expression Biomarkers Relating to the PI3K and/or mTOR Pathway Activation in Biopsied Tumor Tissue

Paired fresh tumor biopsies were only done in 1 subject but not summarized.

Posted

Baseline and Cycle 2 Day 17

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Best Overall Response (Phase 2)

As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2. No data were collected for Phase 2.

Posted

Day 1 up to Day 28

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A

Secondary

Duration of Response (Phase 2)

Duration of response is the time from first documentation of CR or PR to date of first documentation of objective progression or death.

As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2. No data were collected for Phase 2.

Posted

Day 1 to Day 28

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Overall Survival (Phase 2)

Overall survival is the time from randomization date to date of death due to any cause.

As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, there are no efficacy evaluations for Phase 2. No data were collected for Phase 2.

Posted

Day 1 up to Day 28

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.

Secondary

Number of Participants With Evidence of Pathway Signaling Related Genes and/or Proteins in Biopsied Tumor Tissue (Phase 2)

Biomarker evaluation were to be performed on these fresh biopsies, as well as on archival biopsies collected during the study. Samples were to be analyzed for biomarkers indicative of pathway modulation or for genetic markers correlated to drug sensitivity.

Levels of signaling proteins in biopsied tumor tissue was the secondary endpoint for the Phase 2 portion of the study. As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, no data were collected for Phase 2.

Posted

Baseline and Cycle 2 Day 17

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B

Secondary

Change From Baseline in Functional Assessment of Cancer Therapy-Colorectal (FACT-C) (Phase 2)

The FACT-C was to assess health-related quality of life and colorectal cancer (CRC)-related symptoms. It includes a total of 36 items, which are summarized into 6 subscales: physical well-being (7 items), functional well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), CRC subscale (9 items) which addresses a subset of CRC concerns such as diarrhea.

FACT-C was only applicable to the Phase 2 portion of the study. As this study was terminated due to Pfizer portfolio prioritization prior to the Phase 2 portion, no data were collected for Phase 2.

Posted

Day 1 of each cycle

ID	Title	Description
OG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
OG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
OG002

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG0030 affected5 at risk EG0040 affected3 at risk
Eye disorder	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Vision blurred	Eye disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Cheilitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0022 affected3 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0013 affected4 at risk EG0023 affected3 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Haematochezia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Impaired gastric emptying	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Lip disorder	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Lip swelling	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected3 at risk EG0012 affected4 at risk EG0021 affected3 at risk EG003
Oral dysaesthesia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Paraesthesia oral	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Proctalgia	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0012 affected4 at risk EG0021 affected3 at risk EG003
Tongue coated	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG003
Asthenia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Chest pain	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Chills	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Early satiety	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0012 affected4 at risk EG0022 affected3 at risk EG003
Mucosal inflammation	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Oedema peripheral	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Pyrexia	General disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Candida infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Cystitis	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Periorbital infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Pharyngitis streptococcal	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Respiratory tract infection viral	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Blood albumin decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Lymphocyte count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0014 affected4 at risk EG0021 affected3 at risk EG003
Platelet count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG003
Weight decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
White blood cell count decreased	Investigations	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0013 affected4 at risk EG0020 affected3 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Musculoskeletal disorder	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Ataxia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Dizziness	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Head discomfort	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Headache	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0012 affected4 at risk EG0021 affected3 at risk EG003
Lethargy	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Neuropathy peripheral	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Paraesthesia	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Anxiety	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Derailment	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 18.1	Non-systematic Assessment	EG0002 affected3 at risk EG0012 affected4 at risk EG0020 affected3 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Pollakiuria	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0022 affected3 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Hiccups	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Sinus disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Throat irritation	Respiratory, thoracic and mediastinal disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0012 affected4 at risk EG0021 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0001 affected3 at risk EG0011 affected4 at risk EG0021 affected3 at risk EG003
Rash generalised	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0021 affected3 at risk EG003
Flushing	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0011 affected4 at risk EG0020 affected3 at risk EG003
Hot flush	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003
Hypotension	Vascular disorders	MedDRA 18.1	Non-systematic Assessment	EG0000 affected3 at risk EG0010 affected4 at risk EG0020 affected3 at risk EG003

ID	Term
D007414	Intestinal Neoplasms
D005770	Gastrointestinal Neoplasms
D004067	Digestive System Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D004066	Digestive System Diseases
D005767	Gastrointestinal Diseases
D003108	Colonic Diseases
D007410	Intestinal Diseases
D012002	Rectal Diseases

ID	Term
C549060	gedatolisib
D000068258	Bevacizumab
C480833	IFL protocol

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins

ID	Title	Description
BG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.
BG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
BG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
BG003	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3	Participants received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
BG004	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4	Participants received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.
BG005	Total	Total of all reporting groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 150 mg/m^2, leucovorin 320 mg/m^2, 5- fluorouracil (FU) 1920 mg/m^2, and IV bolus of 5-FU 320 mg/m^2 on Days 1 and 15 of each cycle.	0	3	3	3
EG001	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A	Participants received intravenous (IV) infusion of PF-05212384 90 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.	0	4	4	4
EG002	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B	Participants received intravenous (IV) infusion of PF-05212384 110 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.	2	3	3	3
EG003	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3	Participants received intravenous (IV) infusion of PF-05212384 130 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.	2	5	5	5
EG004	PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4	Participants received intravenous (IV) infusion of PF-05212384 150 mg weekly and IV infusions of irinotecan 180 mg/m^2, leucovorin 400 mg/m^2, 5- fluorouracil (FU) 2400 mg/m^2, and IV bolus of 5-FU 400 mg/m^2 on Days 1 and 15 of each cycle.	3	3	3	3