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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
71
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.
37.5mg daily P.O., 4 weeks On 2weeks Off each 42 day cycle. Number of cycles: until progression or unacceptable toxicity develops.
Pfizer Investigational Site
Nagoya, Aichi-ken, Japan
Pfizer Investigational Site
Chiba, Chiba, Japan
Pfizer Investigational Site
Matsuyama, Ehime, Japan
Pfizer Investigational Site
Sapporo, Hokkaido, Japan
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)
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)
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)
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)
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Pfizer Investigational Site
Minoh/Osaka, Japan, Japan
Pfizer Investigational Site
Kochi, Kochi, Japan
Pfizer Investigational Site
Saku, Nagano, Japan
Pfizer Investigational Site
Osakasayama-shi, Osaka, Japan
Pfizer Investigational Site
Takatsuki, Osaka, Japan
Pfizer Investigational Site
Shimotsuke-shi, Tochigi, Japan
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
Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib
Time frame: Cycle 1 Day 15
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
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
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
Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan
Time frame: Cycle 1 Day 15
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
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
Clearance of Irinotecan
CL is calculated as dose divided by AUC 0-∞
Time frame: Cycle 1 Day 15
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
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
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)