Trial Outcomes & Findings for A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer (NCT NCT01925274)
NCT ID: NCT01925274
Last Updated: 2019-01-08
Results Overview
Progression-free survival (PFS) was the time from the first dose of study treatment to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. Median PFS was estimated based on the Kaplan-Meier method.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
19 participants
Primary outcome timeframe
From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years
Results posted on
2019-01-08
Participant Flow
Participant milestones
| Measure |
PF-05212384 + Irinotecan: Arm A
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Overall Study
STARTED
|
7
|
6
|
6
|
|
Overall Study
COMPLETED
|
0
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
7
|
6
|
6
|
Reasons for withdrawal
| Measure |
PF-05212384 + Irinotecan: Arm A
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Overall Study
Death
|
1
|
0
|
0
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
0
|
|
Overall Study
Study terminated by sponsor
|
4
|
0
|
0
|
|
Overall Study
Protocol amendment
|
1
|
3
|
6
|
Baseline Characteristics
A Study Of PF-05212384 Plus Irinotecan Vs Cetuximab Plus Irinotecan In Patients With KRAS And NRAS Wild Type Metastatic Colorectal Cancer
Baseline characteristics by cohort
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Total
n=19 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Customized
<18 years
|
0 participants
7.8 • n=5 Participants
|
0 participants
6.1 • n=7 Participants
|
0 participants
6.7 • n=5 Participants
|
0 participants
n=4 Participants
|
|
Age, Customized
18-64 years
|
5 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
13 participants
n=4 Participants
|
|
Age, Customized
>=65 years
|
2 participants
n=5 Participants
|
2 participants
n=7 Participants
|
2 participants
n=5 Participants
|
6 participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
11 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: From date of first dose until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 yearsPopulation: All participants who were randomized, with KRAS (Kirsten ras oncogene) and NRAS (neuroblastoma ras viral oncogene homolog) wild type status confirmed by central lab, and with treatment arm assignment designated according to randomization. As pre-specified in the protocol, this outcome measure was not analyzed for Japanese Lead-In Cohort.
Progression-free survival (PFS) was the time from the first dose of study treatment to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Objective progression was defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy), with a minimum absolute increase of 5 mm. Median PFS was estimated based on the Kaplan-Meier method.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=4 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=3 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Progression Free Survival (PFS) as Assessed by Investigators
|
3.7 months
Interval 1.5 to 7.4
|
NA months
Less than 50% of the population experienced an event, therefore, median and 95% confidence interval were not calculated. The only individual value was 16.6 months.
|
—
|
SECONDARY outcome
Timeframe: 28 daysPopulation: The analysis population included all participants enrolled into Japanese LIC. As pre-specified in protocol, this outcome measure was not analyzed for reporting arms: "PF-05212384 + Irinotecan: Arm A" and "Cetuximab + Irinotecan: Arm B".
Unacceptable toxicity (according to Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.0) was any of the following occurrences: (1) Grade 4 neutropenia \>7 days, or febrile neutropenia, or Grade 4 thrombocytopenia; (2) Grade \>=3 nausea/vomiting despite optimal antiemetic treatment, or Grade \>=3 diarrhea despite optimal anti diarrheal treatment; (3) unmanageable Grade \>=3 hyperglycemia; (4) mean QTc interval (time from electrocardiogram \[ECG\] Q wave to the end of the T wave corresponding to electrical systole, corrected for heart rate) \>501 msec in triplicate 12-lead ECG, or myocardial infarction, or ventricular arrhythmia; (5) Grade \>=3 non-hematologic toxicity; (6) treatment delay of \>=2 weeks due to study drug related toxicity; (7) persistent, intolerable toxicities which resulted in failure to deliver at least 75% of doses of both PF-05212384 and irinotecan during Cycle 1; (8) Grade \>=2 respiratory toxicities.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Unacceptable Toxicity in Cycle 1 (Japanese LIC Only)
|
0 participants
|
—
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Response evaluable analysis set was used for the analysis of objective response, and it included all participants in the full analysis set (all participants who were randomized, with treatment arm assignment designated according to randomization) who had an adequate baseline assessment of disease and measurable disease.
Percentage of participants with objective response was based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1. Confirmed PR was defined as disappearance of all target lesions. Confirmed PR was defined as \>=30% decrease in sum of the longest dimensions of the target lesions taking the baseline sum as a reference. Confirmed responses were those that persisted on repeat imaging study \>=4 weeks after initial documentation of response.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Percentage of Participants With Objective Response
|
14.3 percentage of participants
Interval 0.4 to 57.9
|
50.0 percentage of participants
Interval 11.8 to 88.2
|
0 percentage of participants
Interval 0.0 to 45.9
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: The analysis population included all participants who achieved CR or PR in Arm A and Arm B. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm "PF 05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)".
For participants with an objective response (CR or PR), duration of response was defined as the time from first documentation of CR or PR to date of first documentation of objective progression or death. Date of first documentation of progression and date of first documentation of CR or PR were based on Investigator's assessment of response.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=1 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=3 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Duration of Response
|
NA months
Only 1 participant achieved CR or PR, therefore, median and 95% confidence interval were not calculated. The only individual value was 5.6 months.
|
NA months
Less than 50% of the population experienced subsequent progression or death, therefore, median and 95% confidence interval were not calculated. The only individual value was 14.8 months.
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Per protocol analysis set, i.e. all participants who were randomized, with KRAS and NRAS wild type status confirmed by central lab and with treatment arm assignment designated according to randomization. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm "PF 05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)".
Overall survival (OS) was defined as the duration from enrollment to death. Participants last known to be alive were censored at date of last contact.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=4 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=3 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Overall Survival (OS)
|
NA months
Interval 3.3 to
Median was not calculated, since less than 50% of population died.
|
NA months
No death occurred in this arm.
|
—
|
SECONDARY outcome
Timeframe: Administration of the first dose of study drug through 28 calendar days after the last administration of study drugPopulation: Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. An SAE was defined as any untoward occurrence at any dose that resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. AEs included both serious and non-serious AEs. Treatment-emergent AEs were those with initial onset or increasing in severity after the first dose of study drug.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
AEs
|
7 participants
|
6 participants
|
6 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
SAEs
|
3 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Administration of the first dose of study drug through 28 calendar days after the last administration of study drugPopulation: Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.0 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Grade 1
|
1 participants
|
2 participants
|
2 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Grade 2
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Grade 3
|
3 participants
|
2 participants
|
4 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Grade 4
|
2 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Common Terminology Criteria for Adverse Events (CTCAE) Grade
Grade 5
|
0 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
The following hematology parameters were evaluated in this study: hemoglobin, white blood cells (WBC) with differential, and platelets.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Laboratory Test (Hematology) Abnormalities
Anemia
|
6 participants
|
6 participants
|
6 participants
|
|
Number of Participants With Laboratory Test (Hematology) Abnormalities
Hemoglobin increased
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Hematology) Abnormalities
Lymphocyte count increased
|
0 participants
|
2 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Hematology) Abnormalities
Lymphopenia
|
5 participants
|
4 participants
|
5 participants
|
|
Number of Participants With Laboratory Test (Hematology) Abnormalities
Neutrophils (absolute)
|
4 participants
|
3 participants
|
5 participants
|
|
Number of Participants With Laboratory Test (Hematology) Abnormalities
Platelets
|
0 participants
|
3 participants
|
1 participants
|
|
Number of Participants With Laboratory Test (Hematology) Abnormalities
White blood cells
|
4 participants
|
4 participants
|
5 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
The following chemistry parameters were evaluated in this study: sodium, potassium, magnesium, chloride, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, total bilirubin, albumin, blood urea nitrogen (BUN) or urea, creatinine, total calcium, glycosylated hemoglobin (HbA1c), glucose, uric acid, phosphorus or phosphate, insulin, and C-peptide.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
ALT
|
2 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Alkaline phosphatase
|
3 participants
|
4 participants
|
4 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
AST
|
2 participants
|
1 participants
|
1 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Total bilirubin
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Creatitine
|
4 participants
|
3 participants
|
6 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypercalcemia
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hyperglycemia
|
6 participants
|
4 participants
|
4 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hyperkalemia
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypermagnesemia
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypernatremia
|
1 participants
|
0 participants
|
1 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypoalbuminemia
|
2 participants
|
4 participants
|
4 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypocalcemia
|
2 participants
|
3 participants
|
3 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypoglycemia
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypokalemia
|
2 participants
|
2 participants
|
3 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypomagnesemia
|
3 participants
|
4 participants
|
1 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hyponatremia
|
2 participants
|
1 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Chemistry) Abnormalities
Hypophosphatemia
|
2 participants
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Urinalysis included urine dipstick for protein and blood: if positive, perform a microscopic analysis. Number of participants with urine protein tested positive is presented.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Laboratory Test (Urinalysis) Abnormalities
|
3 participants
|
1 participants
|
4 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Safety analysis set included all participants who received at least one dose of study treatment, with treatment arm assignment designated according to actual study treatment received.
Coagulation analysis included partial thromboplastin time (PTT) and international normalized ratio (INR) or prothrombin time (PT).
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Laboratory Test (Coagulation) Abnormalities
PTT (number of participants =7, 6, 5)
|
2 participants
|
4 participants
|
0 participants
|
|
Number of Participants With Laboratory Test (Coagulation) Abnormalities
PT (number of participants =7, 5, 6)
|
3 participants
|
3 participants
|
1 participants
|
|
Number of Participants With Laboratory Test (Coagulation) Abnormalities
PT INR
|
1 participants
|
2 participants
|
2 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: QTc analysis set included all participants in the safety analysis set who had at least one ECG assessment after receiving study treatment.
The number of participants with ECG post-baseline maximum absolute values meeting the following criteria was reported: (1) maximum QTc interval ranged from 450 to 480 msec; \>480-500 msec; \>500 msec; (2) maximum QTcB (QT corrected for heart rate using Bazett's formula) interval ranged from 450 to 480 msec; \>480-500 msec; \>500 msec; (3) maximum QTcF (QT corrected for heart rate using Fridericia's formula) interval ranged from 450 to 480 msec; \>480-500 msec; \>500 msec.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=3 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTc interval: 450-480 msec
|
2 participants
|
1 participants
|
1 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTc interval: >480-500 msec
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTc interval: >500 msec
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTcB interval: 450-480 msec
|
3 participants
|
1 participants
|
0 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTcB interval: >480-500 msec
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTcB interval: >500 msec
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTcF interval: >450-480 msec
|
1 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTcF interval: >480-500 msec
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Post-Baseline Maximum Absolute Values Meeting Pre-defined Criteria
Maximum QTcF interval: >500 msec
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: QTc analysis set included all participants in the safety analysis set who had at least one ECG assessment after receiving study treatment.
The number of participants with ECG maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum QTc interval increase from baseline \>30 msec and ≤60 msec; criterion B: maximum QTc interval increase from baseline \>60 msec; criterion C: maximum QTcB interval increase from baseline \>30 msec and ≤60 msec; criterion D: maximum QTcB interval increase from baseline \>60 msec; criterion E: maximum QTcF interval increase from baseline \>30 msec and ≤60 msec; criterion F: maximum QTcF interval increase from baseline \>60 msec.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=3 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Criterion A
|
1 participants
|
1 participants
|
0 participants
|
|
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Criterion B
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Criterion C
|
0 participants
|
1 participants
|
0 participants
|
|
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Criterion D
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Criterion E
|
0 participants
|
0 participants
|
0 participants
|
|
Number of Participants With ECG Maximum Increase From Baseline Meeting Pre-defined Criteria
Criterion F
|
0 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.Population: The pharmacokinetic concentration analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one time point with a concentration measurement recorded. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
Cmax of PF-05212384 was observed directly from data.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of PF-05212384
Cycle 1 Day 9
|
8345 ng/mL
Geometric Coefficient of Variation 19
|
8534 ng/mL
Geometric Coefficient of Variation 10
|
—
|
|
Maximum Plasma Concentration (Cmax) of PF-05212384
Cycle 1 Day 16 (number of participants =5, 6)
|
10120 ng/mL
Geometric Coefficient of Variation 27
|
9670 ng/mL
Geometric Coefficient of Variation 26
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic concentration analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one time point with a concentration measurement recorded. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
Cmax of irinotecan was observed directly from data.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of Irinotecan
Cycle 1 Day 1
|
2283 ng/mL
Geometric Coefficient of Variation 30
|
2123 ng/mL
Geometric Coefficient of Variation 18
|
—
|
|
Maximum Plasma Concentration (Cmax) of Irinotecan
Cycle 2 Day 1 (number of participants =4, 5)
|
1620 ng/mL
Geometric Coefficient of Variation 41
|
1999 ng/mL
Geometric Coefficient of Variation 13
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic concentration analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one time point with a concentration measurement recorded. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
SN-38 is an irinotecan metabolite. Cmax of SN-38 was observed directly from data.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Maximum Plasma Concentration (Cmax) of SN-38
Cycle 1 Day 1
|
23.51 ng/mL
Geometric Coefficient of Variation 32
|
24.25 ng/mL
Geometric Coefficient of Variation 50
|
—
|
|
Maximum Plasma Concentration (Cmax) of SN-38
Cycle 2 Day 1 (number of participants =4, 5)
|
22.81 ng/mL
Geometric Coefficient of Variation 67
|
28.04 ng/mL
Geometric Coefficient of Variation 33
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
Tmax of PF-05212384 was observed directly from data as time of first occurrence.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Time for Maximum Plasma Concentration (Tmax) of PF-05212384
Cycle 1 Day 9
|
0.483 hours
Interval 0.467 to 0.517
|
0.483 hours
Interval 0.467 to 0.5
|
—
|
|
Time for Maximum Plasma Concentration (Tmax) of PF-05212384
Cycle 1 Day 16 (number of participants =5, 6)
|
0.500 hours
Interval 0.467 to 0.517
|
0.500 hours
Interval 0.483 to 0.517
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
Tmax of irinotecan was observed directly from data as time of first occurrence.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Time for Maximum Plasma Concentration (Tmax) of Irinotecan
Cycle 1 Day 1
|
1.50 hours
Interval 1.47 to 1.62
|
1.53 hours
Interval 1.48 to 1.58
|
—
|
|
Time for Maximum Plasma Concentration (Tmax) of Irinotecan
Cycle 2 Day 1 (number of participants =4, 5)
|
1.55 hours
Interval 1.5 to 2.05
|
1.53 hours
Interval 1.5 to 1.57
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
SN-38 is an irinotecan metabolite. Tmax of SN-38 was observed directly from data as time of first occurrence.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Time for Maximum Plasma Concentration (Tmax) of SN-38
Cycle 1 Day 1
|
2.00 hours
Interval 1.5 to 2.18
|
1.98 hours
Interval 1.48 to 2.08
|
—
|
|
Time for Maximum Plasma Concentration (Tmax) of SN-38
Cycle 2 Day 1 (number of participants =4, 5)
|
2.03 hours
Interval 1.53 to 3.98
|
1.93 hours
Interval 1.9 to 2.0
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9 and Cycle 1 Day 16.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Terminal Elimination Half Life (t½) of PF-05212384
Cycle 1 Day 9
|
37.65 hours
Standard Deviation 4.55
|
37.78 hours
Standard Deviation 3.61
|
—
|
|
Terminal Elimination Half Life (t½) of PF-05212384
Cycle 1 Day 16 (number of participants =4, 6)
|
35.10 hours
Standard Deviation 6.90
|
36.07 hours
Standard Deviation 4.56
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Terminal Elimination Half Life (t½) of Irinotecan
Cycle 1 Day 1
|
5.547 hours
Standard Deviation 0.562
|
5.255 hours
Standard Deviation 0.420
|
—
|
|
Terminal Elimination Half Life (t½) of Irinotecan
Cycle 2 Day 1 (number of participants =4, 5)
|
5.293 hours
Standard Deviation 0.488
|
5.344 hours
Standard Deviation 0.719
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
T½ was calculated as loge(2)/kel, where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Only those data points judged to describe the terminal log-linear decline were used in the regression.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=2 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=4 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Terminal Elimination Half Life (t½) of SN-38
Cycle 1 Day 1 (number of participants =2, 3)
|
NA hours
Standard Deviation NA
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 8.05 and 8.56 hours, respectively.
|
9.890 hours
Standard Deviation 0.811
|
—
|
|
Terminal Elimination Half Life (t½) of SN-38
Cycle 2 Day 1
|
NA hours
Standard Deviation NA
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 8.44 and 8.74 hours, respectively.
|
8.840 hours
Standard Deviation 1.091
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of PF-05212384 was determined using linear/log trapezoidal method.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of PF-05212384
|
11530 ng*hr/mL
Geometric Coefficient of Variation 15
|
13390 ng*hr/mL
Geometric Coefficient of Variation 17
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of irinotecan was determined using linear/log trapezoidal method.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of Irinotecan
Cycle 1 Day 1
|
11860 ng*hr/mL
Geometric Coefficient of Variation 23
|
11030 ng*hr/mL
Geometric Coefficient of Variation 29
|
—
|
|
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of Irinotecan
Cycle 2 Day 1 (number of participants =4, 5)
|
8776 ng*hr/mL
Geometric Coefficient of Variation 62
|
10380 ng*hr/mL
Geometric Coefficient of Variation 29
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
AUClast refers to the area under plasma concentration time profile from time zero to the time for the last quantifiable concentration. AUClast of SN-38 (an irinotecan metabolite) was determined using linear/log trapezoidal method.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of SN-38
Cycle 2 Day 1 (number of participants =4, 5)
|
182.4 ng*hr/mL
Geometric Coefficient of Variation 43
|
228.5 ng*hr/mL
Geometric Coefficient of Variation 38
|
—
|
|
Area Under Plasma Concentration Time Profile From Time Zero to the Time for the Last Quantifiable Concentration (AUClast) of SN-38
Cycle 1 Day 1
|
217.0 ng*hr/mL
Geometric Coefficient of Variation 29
|
217.9 ng*hr/mL
Geometric Coefficient of Variation 38
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 24, 72, 120 hours post PF-05212384 infusion on Cycle 1 Day 9.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of PF-05212384 was calculated using the formula: AUCinf = AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-05212384
|
11700 ng*hr/mL
Geometric Coefficient of Variation 15
|
13580 ng*hr/mL
Geometric Coefficient of Variation 17
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre-specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of irinotecan was calculated using the formula: AUCinf = AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Irinotecan
Cycle 1 Day 1
|
12480 ng*hr/mL
Geometric Coefficient of Variation 23
|
11570 ng*hr/mL
Geometric Coefficient of Variation 30
|
—
|
|
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of Irinotecan
Cycle 2 Day 1 (number of participants =4, 5)
|
9216 ng*hr/mL
Geometric Coefficient of Variation 63
|
10950 ng*hr/mL
Geometric Coefficient of Variation 31
|
—
|
SECONDARY outcome
Timeframe: Pre-dose (0 hour), 1.5, 2, 4, 6 and 24 hours post irinotecan infusion on Cycle 1 Day 1 and Cycle 2 Day 1.Population: The pharmacokinetic parameter analysis set included all randomized participants (or enrolled participants to the Japanese LIC) who started treatment and had at least one of the pharmacokinetic parameters of interest estimated. As pre specified in protocol, this outcome measure was not analyzed for reporting arm: "Cetuximab + Irinotecan: Arm B".
AUCinf refers to the area under plasma concentration time profile from time zero extrapolated to infinite time. AUCinf of SN-38 (an irinotecan metabolite) was calculated using the formula: AUCinf = AUClast + (Clast\*/kel), where Clast\* was the predicted plasma concentration at the last quantifiable time point estimated from the log-linear regression analysis.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=2 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=4 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of SN-38
Cycle 1 Day 1 (number of participants =2, 3)
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 218 and 218 ng\*hr/mL, respectively.
|
230.4 ng*hr/mL
Geometric Coefficient of Variation 13
|
—
|
|
Area Under Plasma Concentration Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of SN-38
Cycle 2 Day 1
|
NA ng*hr/mL
Geometric Coefficient of Variation NA
These summary statistics were not calculated, as the number of participants being analyzed was fewer than 3, considered as non-reliable for analysis. The individual values of these two participants were 120 and 215 ng\*hr/mL, respectively.
|
279.7 ng*hr/mL
Geometric Coefficient of Variation 45
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Data for this outcome measure were not collected due to early termination of this study.
Pre defined signaling proteins included Akt (protein kinase B), p-Akt (phosphorylated Akt), p-S6 (phosphorylated ribosomal protein S6), p-Met (phosphorylated Met, a receptor tyrosine kinase), p-mTOR (phosphorylated mammalian target of rapamycin), EGFR (epithelial growth factor receptor), and p-EGFR (phosphorylated EGFR).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 2 yearsPopulation: All participants for whom at least one of these pre-defined gene sequences was analyzed were included.
Pre-defined gene sequences were those related to EGFR, PI3K (phosphoinositide-3 kinase) and other oncogenic pathways; examples included but were not limited to PIK3CA (this gene encodes the catalytic subunit of PI3K), PIK3R1 (this gene encodes the regulatory subunit of PI3K), KRAS, NRAS and BRAF (this gene encodes serine/threonine-protein kinase B-Raf) sequences and PIK3CA gene amplification. Due to early termination of this study, these pre-defined gene sequences were not analyzed, except for KRAS and NRAS. Number of participants who had KRAS and NRAS wild type status confirmed by the central laboratory is presented.
Outcome measures
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 Participants
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 Participants
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Number of Participants With Expression of Pre-defined Gene Sequences in Biopsied Tumor Tissues
Confirmed wild type KRAS
|
4 participants
|
3 participants
|
6 participants
|
|
Number of Participants With Expression of Pre-defined Gene Sequences in Biopsied Tumor Tissues
Confirmed wild type NRAS
|
4 participants
|
3 participants
|
3 participants
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Data for this outcome measure were no longer collected after approval of protocol amendment 4, and data previously collected were insufficient to perform any analysis.
Functional Assessment of Cancer Therapy-Colorectal (FACT-C) was used in this study to assess Health-Related Quality of Life (HRQoL) and CRC-related symptoms in participants enrolled to the randomized portion of the study. The FACT-C is part of the Functional Assessment of Chronic Illness Therapy (FACIT) measurement system, a comprehensive and extensive set of self-reported instruments for the assessment of health-related quality of life in participants with cancer or other chronic illnesses.
Outcome measures
Outcome data not reported
Adverse Events
PF-05212384 + Irinotecan: Arm A
Serious events: 3 serious events
Other events: 7 other events
Deaths: 0 deaths
Cetuximab + Irinotecan: Arm B
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 participants at risk
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 participants at risk
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 participants at risk
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28 day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF 05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Gastrointestinal disorders
Colitis
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Disease progression
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Nervous system disorders
Transient ischaemic attack
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
Other adverse events
| Measure |
PF-05212384 + Irinotecan: Arm A
n=7 participants at risk
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. After one cycle of dosing with PF-05212384, in subsequent cycles, the dose level remained at 110 mg or was escalated based on the occurrences of dose limiting toxicities (DLTs) in previous cycle and at the discretion of the investigator. Participants enrolled in Korea remained at the 110 mg starting dose level of PF-05212384. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF-05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
Cetuximab + Irinotecan: Arm B
n=6 participants at risk
Cetuximab was administered IV every week (Days 1, 8, 15 and 22 of each 28-day cycle) at a starting dose level of 400 mg/m\^2 on Cycle 1 Day 1 followed by 250 mg/m\^2 in subsequent infusions. Irinotecan was administered IV every other week (Days 1 and 15 of each 28-day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of cetuximab and irinotecan were adjusted according to severity of toxicities.
|
PF-05212384 + Irinotecan: Japanese Lead-In Cohort (LIC)
n=6 participants at risk
PF-05212384 was administered intravenously (IV) every week (Days 2, 9, 16 and 23 of each 28-day cycle) at a starting dose level of 110 mg. During Cycle 1, PF-05212384 was only dosed on Days 9, 16 and 23. Irinotecan was administered IV every other week (Days 1 and 15 of each 28 day cycle) at a dose level of 180 mg/m\^2. Both the dose levels of PF 05212384 and irinotecan were adjusted according to severity of toxicities. Infusion of PF-05212384 followed irinotecan infusion by at least 24 hours (+/- 10%).
|
|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
28.6%
2/7
|
50.0%
3/6
|
0.00%
0/6
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/7
|
0.00%
0/6
|
33.3%
2/6
|
|
Blood and lymphatic system disorders
Neutropenia
|
28.6%
2/7
|
16.7%
1/6
|
50.0%
3/6
|
|
Cardiac disorders
Sinus bradycardia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Cardiac disorders
Tachycardia
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Eye disorders
Conjunctivitis allergic
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Gastrointestinal disorders
Abdominal discomfort
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal distension
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain
|
42.9%
3/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain lower
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Colitis
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Colonic fistula
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Constipation
|
42.9%
3/7
|
50.0%
3/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Diarrhoea
|
71.4%
5/7
|
50.0%
3/6
|
50.0%
3/6
|
|
Gastrointestinal disorders
Dry mouth
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Dyspepsia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Anal incontinence
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Gingival bleeding
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Haemorrhoidal haemorrhage
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Haemorrhoids
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Gastrointestinal disorders
Nausea
|
85.7%
6/7
|
50.0%
3/6
|
50.0%
3/6
|
|
Gastrointestinal disorders
Stomatitis
|
71.4%
5/7
|
16.7%
1/6
|
66.7%
4/6
|
|
Gastrointestinal disorders
Vomiting
|
57.1%
4/7
|
16.7%
1/6
|
33.3%
2/6
|
|
General disorders
Asthenia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Chest pain
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Fatigue
|
57.1%
4/7
|
33.3%
2/6
|
16.7%
1/6
|
|
General disorders
Influenza like illness
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
General disorders
Malaise
|
0.00%
0/7
|
0.00%
0/6
|
33.3%
2/6
|
|
General disorders
Mucosal inflammation
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
General disorders
Oedema peripheral
|
28.6%
2/7
|
16.7%
1/6
|
16.7%
1/6
|
|
General disorders
Pyrexia
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Infections and infestations
Anorectal infection
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Infections and infestations
Eye infection
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Infections and infestations
Paronychia
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Infections and infestations
Rash pustular
|
0.00%
0/7
|
33.3%
2/6
|
0.00%
0/6
|
|
Infections and infestations
Upper respiratory tract infection
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Infections and infestations
Urinary tract infection
|
14.3%
1/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Injury, poisoning and procedural complications
Fall
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Laceration
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Skin abrasion
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Investigations
Neutrophil count decreased
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Weight decreased
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Decreased appetite
|
42.9%
3/7
|
33.3%
2/6
|
50.0%
3/6
|
|
Metabolism and nutrition disorders
Dehydration
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
28.6%
2/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
28.6%
2/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
14.3%
1/7
|
33.3%
2/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
42.9%
3/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.3%
1/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Nervous system disorders
Dizziness
|
42.9%
3/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Nervous system disorders
Dysgeusia
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Nervous system disorders
Headache
|
42.9%
3/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Nervous system disorders
Lethargy
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Nervous system disorders
Neuropathy peripheral
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Psychiatric disorders
Depression
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/7
|
33.3%
2/6
|
16.7%
1/6
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Renal and urinary disorders
Pollakiuria
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Renal and urinary disorders
Renal failure
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Reproductive system and breast disorders
Pelvic pain
|
28.6%
2/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
14.3%
1/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dry throat
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.3%
1/7
|
16.7%
1/6
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
14.3%
1/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
42.9%
3/7
|
33.3%
2/6
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
0.00%
0/7
|
0.00%
0/6
|
16.7%
1/6
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/7
|
33.3%
2/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/7
|
33.3%
2/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Rash
|
28.6%
2/7
|
16.7%
1/6
|
33.3%
2/6
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Skin and subcutaneous tissue disorders
Skin fissures
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Vascular disorders
Hypertension
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Vascular disorders
Hypotension
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Investigations
Platelet count decreased
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
14.3%
1/7
|
0.00%
0/6
|
0.00%
0/6
|
|
Infections and infestations
Pneumonia
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/7
|
16.7%
1/6
|
0.00%
0/6
|
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