Unresectable or Metastatic Colorectal Cancer
Conditions
Brief summary
To evaluate the efficacy, safety and pharmacokinetics of sunitinib plus FOLFIRI (irinotecan, 5-FU and l-leucovorin) in the first-line treatment of Japanese mCRC patients
Interventions
DRUGFOLFIRI (The combination regimen of Irinotecan, l-Leucovorin and 5-Fluorouracil)
FOLFIRI treatment with Sunitinib on Day, Irinotecan 180M/M IV , l-Leucovorin 200M/M, 5FU 400M/M bolus and 2400M/M in 46-hour continuous infusion on Day1 each 42 day cycle. Number of Cycles: until progression or unacceptable toxicity develops.
DRUGSunitinib
37.5mg daily P.O., 4 weeks On 2weeks Off each 42 day cycle. Number of cycles: until progression or unacceptable toxicity develops.
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient with histologically- or cytologically-confirmed colorectal adenocarcinoma with unresectable or metastatic disease documented on diagnostic imaging studies. * Patient must have at least one RECIST-defined measurable lesion that has not been treated with prior local therapy.
Exclusion criteria
* History of another primary malignancy within 3 years prior to study entry, with the exception of non-melanoma skin cancer and in situ carcinoma of the uterine cervix. * Current, recent, or planned participation in an experimental treatment drug study other than this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 11 cycles (1 cycle = 6 weeks) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Presented Objective Response: Objective Response Rate (ORR) | Up to 11 cycles (1 cycle = 6 weeks) | 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. |
| Duration of Response (DR) | Up to 11 cycles (1 cycle = 6 weeks) | 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. |
| Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib. | Cycle 1 Day 15 | 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. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib | Cycle 1 Day 15 | — |
| Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC 0-24) of Sunitinib | Cycle 1 Day 15 | AUC 0-24 was determined using the Linear/Log trapezoidal method. |
| Apparent Oral Clearance (CL/F) of Sunitinib | Cycle 1 Day 15 | 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. |
| Maximum Observed Plasma Concentration (Cmax) of Irinotecan | Cycle 1 Day 15 | 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. |
| Overall Survival (OS) | Up to 11 cycles (1 cycle = 6 weeks) | 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. |
| 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 | Cycle 1 Day 15 | 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. |
| Terminal Phase Elimination Half-life (t1/2) of Irinotecan | Cycle 1 Day 15 | Terminal phase half-life of irinotecan was calculated as ln 2/ kel. |
| Clearance of Irinotecan | Cycle 1 Day 15 | CL is calculated as dose divided by AUC 0-∞ |
| Volume of Distribution at Steady State (Vss) of Irinotecan | Cycle 1 Day 15 | 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. |
| Plasma Concentration at Steady State (Css) of 5-FU | Cycle 1 Day 15 | 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. |
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events According to Common Terminology Criteria (CTCAE). | Up to 11 cycles (1 cycle = 6 weeks) | 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. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan | Cycle 1 Day 15 | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 71 |
| Total | 71 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 13 |
| Overall Study | Global Deterioration of Health Status | 4 |
| Overall Study | Objective Progression or Relapse | 42 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Study Terminated by Sponsor | 8 |
| Overall Study | Subject's work scheduling problem | 1 |
| Overall Study | Surgery | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI |
|---|---|
| Age, Customized <=44 years | 6 participants |
| Age, Customized 45 to 64 years | 44 participants |
| Age, Customized >=65 years | 21 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 42 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 71 / 71 |
| serious Total, serious adverse events | 32 / 71 |
Outcome results
Primary
Progression-Free Survival (PFS)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Progression-Free Survival (PFS) | 28.9 weeks |
Secondary
Apparent Oral Clearance (CL/F) of Sunitinib
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.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Apparent Oral Clearance (CL/F) of Sunitinib | 32.9 L/hour | Standard Deviation 6.25 |
Secondary
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC 0-24) of Sunitinib
AUC 0-24 was determined using the Linear/Log trapezoidal method.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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
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
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.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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
Clearance of Irinotecan
CL is calculated as dose divided by AUC 0-∞
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Clearance of Irinotecan | 23.0 L/hour | Standard Deviation 1.53 |
Secondary
Duration of Response (DR)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Duration of Response (DR) | 28.3 weeks |
Secondary
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
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.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib. | SU012662 Cmax | 15.8 ng/mL | Standard Deviation 3.96 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib. | SU012662 Ctrough | 11.3 ng/mL | Standard Deviation 1.41 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib. | Sunitinib Cmax | 54.3 ng/mL | Standard Deviation 6.54 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib. | Sunitinib Ctrough | 41.8 ng/mL | Standard Deviation 16.4 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib. | Total (sunitinib + SU0122662) Cmax | 70.0 ng/mL | Standard Deviation 4.67 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib. | Total (sunitinib + SU0122662) Ctrough | 53.1 ng/mL | Standard Deviation 15.4 |
Secondary
Maximum Observed Plasma Concentration (Cmax) of Irinotecan
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.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) of Irinotecan | Irinotecan Cmax | 1963 ng/mL | Standard Deviation 492 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Maximum Observed Plasma Concentration (Cmax) of Irinotecan | SN-38 Cmax | 25.1 ng/mL | Standard Deviation 7.29 |
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events According to Common Terminology Criteria (CTCAE).
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.
Time frame: Up to 11 cycles (1 cycle = 6 weeks)
Population: Safety analysis set was defined as the same population as the Full Analysis Set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | 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 |
Secondary
Overall Survival (OS)
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.
Time frame: 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).
Secondary
Percentage of Participants Who Presented Objective Response: Objective Response Rate (ORR)
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Percentage of Participants Who Presented Objective Response: Objective Response Rate (ORR) | 36.6 percentage of participants |
Secondary
Plasma Concentration at Steady State (Css) of 5-FU
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.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Plasma Concentration at Steady State (Css) of 5-FU | 650 ng/mL | Standard Deviation 70.5 |
Secondary
Terminal Phase Elimination Half-life (t1/2) of Irinotecan
Terminal phase half-life of irinotecan was calculated as ln 2/ kel.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Terminal Phase Elimination Half-life (t1/2) of Irinotecan | 5.36 hours | Standard Deviation 0.221 |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan | Irinotecan tmax | 2 hours |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan | SN-38 tmax | 4 hours |
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib | Sunitinib Tmax | 6 hours |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib | SU012662 Tmax | 4 hours |
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib | Total (sunitinib + SU0122662) Tmax | 6 hours |
Secondary
Volume of Distribution at Steady State (Vss) of Irinotecan
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.
Time frame: Cycle 1 Day 15
Population: Analysis set was consisted of participants who provided an evaluable sample. Planned number of participants for pharmacokinetic analysis was 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sunitinib 37.5 mg (Schedule 4/2) + FOLFIRI | Volume of Distribution at Steady State (Vss) of Irinotecan | 160 L | Standard Deviation 16.8 |