Trial Outcomes & Findings for A Study Of PF-05212384 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI In Metastatic Colorectal Cancer (NCT NCT01937715)
NCT ID: NCT01937715
Last Updated: 2016-08-18
Results Overview
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).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
18 participants
Primary outcome timeframe
Day 1 up to Day 28
Results posted on
2016-08-18
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
4
|
3
|
5
|
3
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
4
|
2
|
Reasons for withdrawal
| Measure |
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.
|
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.
|
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.
|
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.
|
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.
|
|---|---|---|---|---|---|
|
Overall Study
Death
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
2
|
|
Overall Study
Other
|
0
|
0
|
0
|
3
|
0
|
Baseline Characteristics
A Study Of PF-05212384 Plus FOLFIRI Versus Bevacizumab Plus FOLFIRI In Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
Total
n=18 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
41.7 years
STANDARD_DEVIATION 11.7 • n=5 Participants
|
54.3 years
STANDARD_DEVIATION 10.1 • n=7 Participants
|
63.3 years
STANDARD_DEVIATION 11.6 • n=5 Participants
|
65.8 years
STANDARD_DEVIATION 9 • n=4 Participants
|
54.3 years
STANDARD_DEVIATION 5.5 • n=21 Participants
|
56.9 years
STANDARD_DEVIATION 12.1 • n=10 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
7 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
11 Participants
n=10 Participants
|
PRIMARY outcome
Timeframe: Day 1 up to Day 28Population: 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.
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).
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Percentage of Participants With Dose-Limiting Toxicities (DLTs) in First Cycle of Therapy
|
20.0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
0 percentage of participants
|
66.7 percentage of participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1) up to disease progression or death whichever occurred first (up to 18 months)Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Every 8 weeks from Cycle 1 Day 1 until 28 days of last dosePopulation: All participants in the full analysis (FA) set who had measureable disease and an adequate baseline assessment of the disease.
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).
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=2 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With Best Overall Response (Phase 1B)
PD
|
1 participants
|
2 participants
|
2 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Best Overall Response (Phase 1B)
SD
|
3 participants
|
0 participants
|
2 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Best Overall Response (Phase 1B)
PR
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Best Overall Response (Phase 1B)
Indeterminant
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Baseline up to final study evaluation (within 28 days of last dose)Population: All participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
# of Participants with Grade 3 or 4 AEs
|
3 participants
|
0 participants
|
3 participants
|
3 participants
|
3 participants
|
|
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
# of Participants D/C'd Study Due to AEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
# of Participants D/C'd PF-05212384 Due to AEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
|
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
Number (#) of Participants with AEs
|
5 participants
|
3 participants
|
4 participants
|
3 participants
|
3 participants
|
|
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
# of Participants with SAEs
|
2 participants
|
0 participants
|
0 participants
|
2 participants
|
3 participants
|
|
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
# of Participants with Grade 5 AEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With All Causality Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations by Relationship and Seriousness
Number of Participants D/C'd FOLFIRI Due to AEs
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline up to final study evaluation (within 28 days of last dose)Population: All participants who received at least 1 dose of study medication.
An AE was any untoward medical occurrence without regard to causality in a participant who received study drug.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Gastrointestinal disorders
|
5 participants
|
3 participants
|
4 participants
|
3 participants
|
3 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
General disorders & administration site conditions
|
4 participants
|
2 participants
|
2 participants
|
2 participants
|
2 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Hepatobiliary disorders
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Immune system disorders
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Infections and infestations
|
1 participants
|
1 participants
|
3 participants
|
1 participants
|
1 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Injury, poisoning and procedural complications
|
0 participants
|
0 participants
|
3 participants
|
0 participants
|
0 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Investigations
|
2 participants
|
1 participants
|
4 participants
|
1 participants
|
2 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Metabolism and nutrition disorders
|
3 participants
|
2 participants
|
3 participants
|
1 participants
|
2 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Musculoskeletal and connective tissue disorders
|
1 participants
|
1 participants
|
4 participants
|
1 participants
|
1 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Nervous system disorders
|
2 participants
|
0 participants
|
2 participants
|
3 participants
|
1 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Psychiatric disorders
|
0 participants
|
3 participants
|
2 participants
|
0 participants
|
2 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Renal and urinary disorders
|
1 participants
|
0 participants
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Respiratory, thoracic and mediastinal disorders
|
3 participants
|
1 participants
|
1 participants
|
3 participants
|
1 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Skin and subcutaneous tissue disorders
|
2 participants
|
1 participants
|
3 participants
|
2 participants
|
3 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Vascular disorders
|
1 participants
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Blood and lymphatic system disorders
|
1 participants
|
0 participants
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With All Causality AEs by System Organ Class (SOC)
Eye disorders
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline up to final study evaluation (within 28 days of last dose)Population: All participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
Any AEs, Grade 1
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
Any AEs, Grade 2
|
1 participants
|
3 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
Any AEs, Grade 3
|
2 participants
|
0 participants
|
3 participants
|
3 participants
|
3 participants
|
|
Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
Any AEs, Grade 4
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
Any AEs, Grade 5
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent AEs by Worst On-Study Grade
Any AEs, total
|
5 participants
|
3 participants
|
4 participants
|
3 participants
|
3 participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 15 of each cyclePopulation: All participants who received at least 1 dose of study medication.
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 hematological test abnormalities.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=2 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With Hematological Test Abnormalities
Anemia
|
5 participants
|
3 participants
|
4 participants
|
3 participants
|
2 participants
|
|
Number of Participants With Hematological Test Abnormalities
Hemoglobin increased
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hematological Test Abnormalities
Lymphocyte count increased
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hematological Test Abnormalities
Lymphopenia
|
3 participants
|
2 participants
|
2 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Hematological Test Abnormalities
Neutrophils (Absolute)
|
2 participants
|
0 participants
|
4 participants
|
2 participants
|
2 participants
|
|
Number of Participants With Hematological Test Abnormalities
Platelets
|
2 participants
|
0 participants
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Hematological Test Abnormalities
White blood cells
|
3 participants
|
1 participants
|
3 participants
|
3 participants
|
2 participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cyclesPopulation: All participants who received at least 1 dose of study medication. n=number of participants evaluated against criteria.
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Coagulation test abnormalities.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With Coagulation Test Abnormalities
Partial thromboplastin time (N=3, 4, 3, 5, 2)
|
2 participants
|
1 participants
|
0 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Coagulation Test Abnormalities
Prothrombin time (PT) (N=3, 3,2, 5, 1)
|
1 participants
|
1 participants
|
0 participants
|
2 participants
|
1 participants
|
|
Number of Participants With Coagulation Test Abnormalities
PT INR (N=3, 4, 3, 5, 2)
|
0 participants
|
1 participants
|
0 participants
|
2 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 15 of each cyclePopulation: All participants who received at least 1 dose of study medication. n=number of participants evaluated against criteria.
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Chemistry test abnormalities.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=2 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With Chemistry Test Abnormalities
Hyperkalemia
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Alanine aminotransferase
|
3 participants
|
0 participants
|
1 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Alkaline phosphatase
|
3 participants
|
3 participants
|
2 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Aspartate aminotransferase
|
4 participants
|
2 participants
|
2 participants
|
2 participants
|
1 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Bilirubin (total)
|
1 participants
|
0 participants
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Creatinine
|
4 participants
|
1 participants
|
2 participants
|
3 participants
|
2 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hyperglycemia
|
5 participants
|
2 participants
|
3 participants
|
1 participants
|
2 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hypermagnesemia
|
0 participants
|
0 participants
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hypoalbuminemia
|
3 participants
|
2 participants
|
2 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hypocalcemia
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hypoglycemia
|
0 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hypokalemia
|
0 participants
|
2 participants
|
2 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hypomagnesemia
|
1 participants
|
0 participants
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hyponatremia
|
4 participants
|
3 participants
|
2 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Chemistry Test Abnormalities
Hypohphosphatemia
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Day 1 and Day 15 of Cycle 1, Day 1 of Cycle 2 and subsequent cyclesPopulation: All participants who received at least 1 dose of study medication.
Number of participants with NCI CTCAE version 4.0 grade 1 to 4 Urinalysis test abnormalities.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=2 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants With Urinalysis Test Abnormalities
|
2 participants
|
2 participants
|
1 participants
|
1 participants
|
2 participants
|
SECONDARY outcome
Timeframe: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
Maximum Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil
PF-05212384 (n=3,4,2,5,3)
|
8222 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 35
|
8245 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 25
|
6554 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 66
|
33470 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Mean value is provided for Dose level 2B.
|
10250 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 11
|
|
Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil
Irinotecan (n=3,4,1,5,3)
|
1585 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 17
|
1782 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 4
|
1323 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 43
|
1550 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
1755 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 6
|
|
Maximum Observed Plasma Concentration (Cmax): PF-05212384, Irinotecan, and Fluorouracil
Fluorouracil (n=3,4,1,4,3)
|
26790 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 18
|
18390 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 85
|
18950 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 41
|
44000 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
26920 nanogram (ng)/milliliter (mL)
Geometric Coefficient of Variation 3
|
SECONDARY outcome
Timeframe: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1. Fluorouracil: Cycle 1 Day 1.Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
Time to Reach Maximum Observed Plasma Concentration of PF-05212384, Irinotecan, and Fluorouracil
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil
PF-05212384 (n=3,4,2,5,3)
|
0.500 hour (hr)
Interval 0.383 to 0.5
|
0.500 hour (hr)
Interval 0.45 to 0.5
|
0.550 hour (hr)
Interval 0.45 to 0.617
|
0.500 hour (hr)
Interval 0.5 to 0.5
|
0.500 hour (hr)
Interval 0.483 to 1.03
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil
Irinotecan (n=3,4,1,5,3)
|
2.25 hour (hr)
Interval 1.98 to 2.5
|
2.02 hour (hr)
Interval 1.98 to 2.02
|
2.04 hour (hr)
Interval 2.0 to 2.15
|
1.95 hour (hr)
Interval 1.95 to 1.95
|
2.00 hour (hr)
Interval 1.98 to 2.02
|
|
Time to Reach Maximum Observed Plasma Concentration (Tmax): PF-05212384, Irinotecan, and Fluorouracil
Fluorouracil (n=3,4,1,4,3)
|
0.125 hour (hr)
Interval 0.067 to 0.25
|
0.0830 hour (hr)
Interval 0.033 to 0.15
|
0.167 hour (hr)
Interval 0.167 to 0.233
|
0.0830 hour (hr)
Interval 0.083 to 0.083
|
0.150 hour (hr)
Interval 0.15 to 46.2
|
SECONDARY outcome
Timeframe: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
Area Under the Curve From Time Zero to Last Quantifiable Concentration of PF-05212384, and Irinotecan
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan
Irinotecan (n=3,4,1,4,3)
|
10340 ng*hr/mL
Geometric Coefficient of Variation 15
|
12510 ng*hr/mL
Geometric Coefficient of Variation 8
|
9164 ng*hr/mL
Geometric Coefficient of Variation 53
|
8050 ng*hr/mL
Geometric Coefficient of Variation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
11030 ng*hr/mL
Geometric Coefficient of Variation 28
|
|
Area Under the Curve From Time Zero to Last Quantifiable Concentration (AUClast): PF-05212384 and Irinotecan
PF-05212384 (n=3,4,1,5,3)
|
13570 ng*hr/mL
Geometric Coefficient of Variation 40
|
11460 ng*hr/mL
Geometric Coefficient of Variation 22
|
9129 ng*hr/mL
Geometric Coefficient of Variation 33
|
30700 ng*hr/mL
Geometric Coefficient of Variation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
14760 ng*hr/mL
Geometric Coefficient of Variation 34
|
SECONDARY outcome
Timeframe: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time of PF-05212384 and Irinotecan
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=1 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan
Irinotecan
|
10900 ng*hr/mL
Geometric Coefficient of Variation 16
|
13120 ng*hr/mL
Geometric Coefficient of Variation 10
|
9709 ng*hr/mL
Geometric Coefficient of Variation 54
|
8350 ng*hr/mL
Geometric Coefficient of Variation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
11560 ng*hr/mL
Geometric Coefficient of Variation 29
|
|
Area Under the Plasma Concentration-Time Profile From Time 0 Extrapolated to Infinite Time (AUCinf): PF-05212384 and Irinotecan
PF-05212384
|
13830 ng*hr/mL
Geometric Coefficient of Variation 40
|
11820 ng*hr/mL
Geometric Coefficient of Variation 22
|
9289 ng*hr/mL
Geometric Coefficient of Variation 32
|
30900 ng*hr/mL
Geometric Coefficient of Variation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
15270 ng*hr/mL
Geometric Coefficient of Variation 34
|
SECONDARY outcome
Timeframe: PF-05212384: Cycle 1 Day 3. Irinotecan: Cycle 1 Day 1.Population: Randomized participants (or enrolled participants for Phase 1B) who started treatment and who had at least one of the pharmacokinetic parameters of interest estimated.
Terminal Elimination Half-Life of PF-05212384 and Irinotecan
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=1 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan
PF-05212384
|
29.18 hour
Standard Deviation 6.9909
|
33.63 hour
Standard Deviation 1.3503
|
27.90 hour
Standard Deviation 3.3695
|
29.2 hour
Standard Deviation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
36.97 hour
Standard Deviation 1.9035
|
|
Terminal Elimination Half-Life (t1/2): PF-05212384 and Irinotecan
Irinotecan
|
5.360 hour
Standard Deviation 0.40817
|
5.127 hour
Standard Deviation 0.70692
|
5.533 hour
Standard Deviation 1.1621
|
4.97 hour
Standard Deviation NA
Summary statistics were not presented if fewer than 3 subjects had reportable parameter values. Individual value is provided for Dose level 2B.
|
5.107 hour
Standard Deviation 0.40427
|
SECONDARY outcome
Timeframe: Baseline, Cycle 1 Day 1, and Cycle 2 Day 2Population: All participants who received at least 1 dose of study medication.
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.
Outcome measures
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 Participants
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 Participants
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.
|
|---|---|---|---|---|---|
|
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
QTcF Interval increase >30 to =<60 msec
|
1 participants
|
1 participants
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
QTcF Interval <450 msec
|
3 participants
|
3 participants
|
4 participants
|
3 participants
|
3 participants
|
|
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
QTcF Interval 450-480 msec
|
2 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
QTcF Interval >480-500 msec
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
QTcF Interval >500 msec
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
QTcF Interval increase =< 30 msec
|
4 participants
|
2 participants
|
3 participants
|
3 participants
|
3 participants
|
|
Number of Participants Meeting Maximum Post-Baseline QTc Interval Values
QTcF Interval increase >60
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Baseline and Cycle 2 Day 17Population: Paired fresh tumor biopsies were only done in 1 subject but not summarized.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Cycle 2 Day 17Population: Paired fresh tumor biopsies were only done in 1 subject but not summarized.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 up to Day 28Population: 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.
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).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 to Day 28Population: 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.
Duration of response is the time from first documentation of CR or PR to date of first documentation of objective progression or death.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 up to Day 28Population: 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.
Overall survival is the time from randomization date to date of death due to any cause.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Baseline and Cycle 2 Day 17Population: 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.
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.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Day 1 of each cyclePopulation: 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.
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.
Outcome measures
Outcome data not reported
Adverse Events
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
Serious events: 2 serious events
Other events: 5 other events
Deaths: 0 deaths
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 participants at risk
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.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
General disorders
Pyrexia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Periorbital infection
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Sepsis
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
Other adverse events
| Measure |
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 1
n=3 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2A
n=4 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 2B
n=3 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 3
n=5 participants at risk
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.
|
PF-05212384+5-FU+Irinotecan+Leucovorin:Dose Level 4
n=3 participants at risk
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.
|
|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Eye disorders
Eye disorder
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Eye disorders
Vision blurred
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Abdominal discomfort
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Abdominal distension
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Diarrhoea
|
33.3%
1/3 • Baseline to end of treatment
|
75.0%
3/4 • Baseline to end of treatment
|
100.0%
3/3 • Baseline to end of treatment
|
60.0%
3/5 • Baseline to end of treatment
|
100.0%
3/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Dry mouth
|
33.3%
1/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
40.0%
2/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
33.3%
1/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Lip disorder
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Lip swelling
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
60.0%
3/5 • Baseline to end of treatment
|
100.0%
3/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Oral dysaesthesia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Paraesthesia oral
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Proctalgia
|
33.3%
1/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Stomatitis
|
33.3%
1/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
60.0%
3/5 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Tongue coated
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Gastrointestinal disorders
Vomiting
|
66.7%
2/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
40.0%
2/5 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
|
General disorders
Asthenia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
General disorders
Chest pain
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
General disorders
Chills
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
General disorders
Early satiety
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
General disorders
Fatigue
|
33.3%
1/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
40.0%
2/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
General disorders
Mucosal inflammation
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
General disorders
Oedema peripheral
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
General disorders
Pyrexia
|
33.3%
1/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Hepatobiliary disorders
Cholangitis
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Candida infection
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Cystitis
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Herpes zoster
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Periorbital infection
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Pharyngitis streptococcal
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Injury, poisoning and procedural complications
Ligament sprain
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Investigations
Blood albumin decreased
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/3 • Baseline to end of treatment
|
100.0%
4/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
|
Investigations
Platelet count decreased
|
0.00%
0/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Investigations
Weight decreased
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
40.0%
2/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Investigations
White blood cell count decreased
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
60.0%
3/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
40.0%
2/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
33.3%
1/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/3 • Baseline to end of treatment
|
75.0%
3/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal disorder
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Ataxia
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Disturbance in attention
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Nervous system disorders
Head discomfort
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Headache
|
0.00%
0/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Nervous system disorders
Lethargy
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Neuropathy peripheral
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Paraesthesia
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Psychiatric disorders
Anxiety
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Psychiatric disorders
Derailment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Psychiatric disorders
Insomnia
|
66.7%
2/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
33.3%
1/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Sinus disorder
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
33.3%
1/3 • Baseline to end of treatment
|
50.0%
2/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
66.7%
2/3 • Baseline to end of treatment
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
1/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash generalised
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Vascular disorders
Flushing
|
0.00%
0/3 • Baseline to end of treatment
|
25.0%
1/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
|
Vascular disorders
Hot flush
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/5 • Baseline to end of treatment
|
33.3%
1/3 • Baseline to end of treatment
|
|
Vascular disorders
Hypotension
|
0.00%
0/3 • Baseline to end of treatment
|
0.00%
0/4 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
20.0%
1/5 • Baseline to end of treatment
|
0.00%
0/3 • Baseline to end of treatment
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
- Publication restrictions are in place
Restriction type: OTHER