Trial Outcomes & Findings for Study Of Sunitinib With FOLFIRI In Colorectal Cancer (NCT NCT00668863)
NCT ID: NCT00668863
Last Updated: 2011-10-17
Results Overview
PFS is defined as the time from the date of enrollment to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. PFS data was censored on the day following the date of the last tumor assessment documenting absence of progressive disease for patients who 1) were given anti-tumor treatment other than the study treatment prior to observing objective tumor progression; 2) were removed from the study prior to documentation of objective tumor progression; and 3) were ongoing at the time of the analysis.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
71 participants
Primary outcome timeframe
Up to 11 cycles (1 cycle = 6 weeks)
Results posted on
2011-10-17
Participant Flow
Participant milestones
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Overall Study
STARTED
|
71
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
71
|
Reasons for withdrawal
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Overall Study
Objective Progression or Relapse
|
42
|
|
Overall Study
Adverse Event
|
13
|
|
Overall Study
Study Terminated by Sponsor
|
8
|
|
Overall Study
Global Deterioration of Health Status
|
4
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Surgery
|
1
|
|
Overall Study
Subject's work scheduling problem
|
1
|
|
Overall Study
Physician Decision
|
1
|
Baseline Characteristics
Study Of Sunitinib With FOLFIRI In Colorectal Cancer
Baseline characteristics by cohort
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=71 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Age, Customized
<=44 years
|
6 participants
n=5 Participants
|
|
Age, Customized
45 to 64 years
|
44 participants
n=5 Participants
|
|
Age, Customized
>=65 years
|
21 participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
42 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 11 cycles (1 cycle = 6 weeks)Population: Full Analysis Set was defined as all enrolled subjects who met the following criteria :1) Those who were diagnosed as having adenocarcinoma of the colon or rectum with documented locally advanced or metastatic disease and 2) those who received at least one dose of the study medication.
PFS is defined as the time from the date of enrollment to the date of the first documentation of objective tumor progression or death due to any cause, whichever occurs first. PFS data was censored on the day following the date of the last tumor assessment documenting absence of progressive disease for patients who 1) were given anti-tumor treatment other than the study treatment prior to observing objective tumor progression; 2) were removed from the study prior to documentation of objective tumor progression; and 3) were ongoing at the time of the analysis.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=71 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Progression-Free Survival (PFS)
|
28.9 weeks
Interval 20.3 to 40.0
|
SECONDARY outcome
Timeframe: Up to 11 cycles (1 cycle = 6 weeks)Population: Median OS was not calculable due to the large number of censored events (63 out of 71 were censored).
OS is defined as the time from the date of enrollment to the date of death due to any cause. OS data was censored on the day following the date of the last contact at which the patient is known to be alive.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 11 cycles (1 cycle = 6 weeks)Population: Full Analysis Set was defined as all enrolled subjects who met the following criteria :1) Those who were diagnosed as having adenocarcinoma of the colon or rectum with documented locally advanced or metastatic disease and 2) those who received at least one dose of the study medication.
ORR is defined as the percentage of participants with best overall response of either a confirmed complete (CR) or partial response (PR) relative to the number of participants in FAS. Based on the response evaluation criteria in solid tumors (RECIST), CR is defined as the disappearance of all target lesions and PR is defined as a greater than or equal to 30% decrease in the sum of the longest dimensions of the target lesion.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=71 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Percentage of Participants Who Presented Objective Response: Objective Response Rate (ORR)
|
36.6 percentage of participants
Interval 25.5 to 48.9
|
SECONDARY outcome
Timeframe: Up to 11 cycles (1 cycle = 6 weeks)Population: Analysis set was consisted of participants with a confirmed objective tumor response (CR or PR) among Full Analysis Set.
DR is defined as the time from the first objective documentation of complete or partial response that is subsequently confirmed to the first documentation of disease progression or to death due to any cause, whichever occurs first. The definition of censorship is the same as PFS.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=26 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Duration of Response (DR)
|
28.3 weeks
Interval 25.1 to 44.3
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Plasma concentrations were assessed at predose, 2, 4, 6, 8, and 24 hours postdose and Cmax and Ctrough of sunitinib, its metabolite SU012662, and the total (sunitinib + SU0122662) were determined.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
Sunitinib Cmax
|
54.3 ng/mL
Standard Deviation 6.54
|
|
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
Sunitinib Ctrough
|
41.8 ng/mL
Standard Deviation 16.4
|
|
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
SU012662 Cmax
|
15.8 ng/mL
Standard Deviation 3.96
|
|
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
SU012662 Ctrough
|
11.3 ng/mL
Standard Deviation 1.41
|
|
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
Total (sunitinib + SU0122662) Cmax
|
70.0 ng/mL
Standard Deviation 4.67
|
|
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
Total (sunitinib + SU0122662) Ctrough
|
53.1 ng/mL
Standard Deviation 15.4
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib
Sunitinib Tmax
|
6 hours
Interval 0.0 to 8.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib
SU012662 Tmax
|
4 hours
Interval 4.0 to 8.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib
Total (sunitinib + SU0122662) Tmax
|
6 hours
Interval 4.0 to 8.0
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
AUC 0-24 was determined using the Linear/Log trapezoidal method.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC 0-24) of Sunitinib
Sunitinib AUC 0-24
|
1161 ng.h/mL
Standard Deviation 200
|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC 0-24) of Sunitinib
SU012662 AUC 0-24
|
346 ng.h/mL
Standard Deviation 108
|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC 0-24) of Sunitinib
Total (sunitinib + SU0122662) AUC 0-24
|
1507 ng.h/mL
Standard Deviation 114
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Apparent Oral Clearance (CL/F) of Sunitinib
|
32.9 L/hour
Standard Deviation 6.25
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Plasma samples were assessed at prior to initiation of irinotecan (and l-leucovorin) infusion, 1, 2 (predose for 5-FU bolus), 4, 8, and 24 hours after initiation of irinotecan infusion, and Cmax of irinotecan and its metabolite SN-38 were determined.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Maximum Observed Plasma Concentration (Cmax) of Irinotecan
SN-38 Cmax
|
25.1 ng/mL
Standard Deviation 7.29
|
|
Maximum Observed Plasma Concentration (Cmax) of Irinotecan
Irinotecan Cmax
|
1963 ng/mL
Standard Deviation 492
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan
Irinotecan tmax
|
2 hours
Interval 1.0 to 2.0
|
|
Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan
SN-38 tmax
|
4 hours
Interval 2.0 to 4.0
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
AUC last of irinotecan and its metabolite SN-38 were calculated using the Linear/Log trapezoidal method. AUC∞ of irinotecan was calculated using following equation; AUC last+(C\*t/kel), where Ct\* is the estimated concentration at the time of the last quantifiable concentration, kel is terminal phase rate constant that is estimated as the absolute value of the slope of a linear regression during the terminal phase of the natural-logarithm (ln) transformed concentration-time profile.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC Last) and Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC ∞) of Irinotecan
Irinotecan AUC last
|
13100 ng.h/mL
Standard Deviation 1323
|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC Last) and Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC ∞) of Irinotecan
Irinotecan AUC ∞
|
13800 ng.h/mL
Standard Deviation 1400
|
|
Area Under the Plasma Concentration Versus Time Curve From Time 0 to the Time of the Last Measurable Concentration (AUC Last) and Area Under the Plasma Concentration Versus Time Curve From Time 0 to Infinity (AUC ∞) of Irinotecan
SN-38 AUC last
|
274 ng.h/mL
Standard Deviation 117
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Terminal phase half-life of irinotecan was calculated as ln 2/ kel.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Terminal Phase Elimination Half-life (t1/2) of Irinotecan
|
5.36 hours
Standard Deviation 0.221
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
CL is calculated as dose divided by AUC 0-∞
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Clearance of Irinotecan
|
23.0 L/hour
Standard Deviation 1.53
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Vss was calculated using following equation: CL x mean residence time (MRT), where MRT = the area under the first moment curve from zero time to infinity (AUMC 0-∞)/AUC 0-∞- (infusion time/2), AUMC 0-∞ = the area under the first moment curve from zero time to time t (AUMC t)+ ((t x Ct\*)/ kel) + (Ct\* / kel\^2), AUMC t is calculated using the linear trapezoidal method.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Volume of Distribution at Steady State (Vss) of Irinotecan
|
160 L
Standard Deviation 16.8
|
SECONDARY outcome
Timeframe: Cycle 1 Day 15Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
Concentration at 22 hour post start of 5-FU infusion were to be used as Css if 5-FU concentrations suggested steady state at 22 hours time point.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=3 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Plasma Concentration at Steady State (Css) of 5-FU
|
650 ng/mL
Standard Deviation 70.5
|
SECONDARY outcome
Timeframe: Up to 11 cycles (1 cycle = 6 weeks)Population: Safety analysis set was defined as the same population as the Full Analysis Set.
Any untoward medical occurrence in a patient who received study drug was considered an adverse event (AE), without regard to possibility of causal relationship. Treatment-emergent adverse events (TEAE): those which occurred or worsened after baseline. An adverse event resulting in any of the following outcomes, or deemed to be significant for any other reason, was considered to be a serious adverse event (SAE): death; initial or prolonged inpatient hospitalization; a life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Outcome measures
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=71 Participants
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events According to Common Terminology Criteria (CTCAE).
Treatment emergent adverse events
|
71 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events According to Common Terminology Criteria (CTCAE).
Serious adverse events
|
32 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events According to Common Terminology Criteria (CTCAE).
CTCAE grade 3 or 4 adverse events
|
70 Participants
|
|
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events According to Common Terminology Criteria (CTCAE).
CTCAE grade 5 adverse events
|
1 Participants
|
Adverse Events
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
Serious events: 32 serious events
Other events: 71 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=71 participants at risk
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Leukopenia
|
2.8%
2/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Lymphadenitis
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Neutropenia
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
2.8%
2/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Cardiac disorders
Myocardial infarction
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Diarrhoea
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Gastric dilatation
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Gastrointestinal perforation
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Haemorrhoids
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Ileus
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
2.8%
2/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Nausea
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Pneumatosis intestinalis
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Vomiting
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Fatigue
|
2.8%
2/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Pyrexia
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Abdominal abscess
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Infection
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Influenza
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Localised infection
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Pneumonia
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Septic shock
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Injury, poisoning and procedural complications
Wound complication
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Neutrophil count decreased
|
4.2%
3/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
White blood cell count decreased
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Dehydration
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Cerebral infarction
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Renal and urinary disorders
Hydronephrosis
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Vascular disorders
Hypertension
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Vascular disorders
Thrombosis
|
1.4%
1/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
Other adverse events
| Measure |
Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI
n=71 participants at risk
Sunitinib was orally administered at 37.5 mg once daily for 4 consecutive weeks followed by a 2-week rest period to comprise a complete cycle of 6 weeks (Schedule 4/2). Sunitinib was given in combination with FOLFIRI, which was administered in the standard fashion every 2 weeks: Irinotecan (180 mg/m\^2) and l-leucovorin (200 mg/m\^2) was infused intravenously on Day 1, immediately followed by 5 FU bolus (400 mg/m\^2) and 46-hour (2400 mg/m\^2) infusion. FOLFIRI was given on Days 1, 15, and 29 in each 6-week cycle of sunitinib administration.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
15.5%
11/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Neutropenia
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Endocrine disorders
Hypothyroidism
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Eye disorders
Eyelid oedema
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal distension
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal pain
|
18.3%
13/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
14.1%
10/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Cheilitis
|
11.3%
8/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Constipation
|
40.8%
29/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Diarrhoea
|
77.5%
55/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Dyspepsia
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Gingivitis
|
18.3%
13/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Haemorrhoids
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Nausea
|
76.1%
54/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Stomatitis
|
50.7%
36/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Gastrointestinal disorders
Vomiting
|
54.9%
39/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Face oedema
|
11.3%
8/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Fatigue
|
66.2%
47/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Malaise
|
11.3%
8/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Mucosal inflammation
|
12.7%
9/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Oedema
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Oedema peripheral
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
General disorders
Pyrexia
|
38.0%
27/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Infection
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Infections and infestations
Nasopharyngitis
|
16.9%
12/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Alanine aminotransferase increased
|
25.4%
18/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Aspartate aminotransferase increased
|
22.5%
16/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood albumin decreased
|
31.0%
22/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood alkaline phosphatase increased
|
18.3%
13/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood bilirubin increased
|
9.9%
7/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood cholesterol increased
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood creatinine increased
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood glucose increased
|
12.7%
9/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood lactate dehydrogenase increased
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood phosphorus decreased
|
21.1%
15/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood potassium decreased
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood thyroid stimulating hormone increased
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Blood triglycerides increased
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
C-reactive protein increased
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Gamma-glutamyltransferase increased
|
15.5%
11/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Haemoglobin decreased
|
39.4%
28/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Lymphocyte count decreased
|
33.8%
24/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Neutrophil count decreased
|
91.5%
65/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Platelet count decreased
|
78.9%
56/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Protein total decreased
|
8.5%
6/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Protein urine present
|
9.9%
7/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Red blood cell count decreased
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
Weight decreased
|
9.9%
7/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Investigations
White blood cell count decreased
|
90.1%
64/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
70.4%
50/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Dehydration
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
15.5%
11/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Dizziness
|
16.9%
12/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Dysgeusia
|
49.3%
35/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Headache
|
16.9%
12/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Nervous system disorders
Neuropathy peripheral
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Psychiatric disorders
Insomnia
|
15.5%
11/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Renal and urinary disorders
Proteinuria
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.9%
7/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
14.1%
10/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
14.1%
10/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
62.0%
44/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
46.5%
33/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
7.0%
5/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Rash
|
16.9%
12/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Skin and subcutaneous tissue disorders
Skin discolouration
|
31.0%
22/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Vascular disorders
Flushing
|
5.6%
4/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
|
Vascular disorders
Hypertension
|
33.8%
24/71 • Up to 11 cycles (1 cycle = 6 weeks)
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.
|
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