Back to resultsStudy Of Sunitinib With FOLFIRI In Colorectal Cancer
Primary Purpose
Unresectable or Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 2
Locations
Japan
Study Type
Interventional
Intervention
FOLFIRI (The combination regimen of Irinotecan, l-Leucovorin and 5-Fluorouracil)
Sunitinib
Sponsored by
About this trial
This is an interventional treatment trial for Unresectable or Metastatic Colorectal Cancer
Eligibility Criteria
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.
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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 to Reach Maximum Plasma Concentration (Tmax) of Sunitinib
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.
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.
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 to Reach Maximum Plasma Concentration (Tmax) of Irinotecan
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.
Terminal Phase Elimination Half-life (t1/2) of Irinotecan
Terminal phase half-life of irinotecan was calculated as ln 2/ kel.
Clearance of Irinotecan
CL is calculated as dose divided by AUC 0-∞
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00668863
Brief Title
Study Of Sunitinib With FOLFIRI In Colorectal Cancer
Official Title
A Phase II Study Of Sunitinib In Combination With Irinotecan, L-leucovorin, And 5-Fluorouracil In Patients With Unresectable Or Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
October 2011
Overall Recruitment Status
Completed
Study Start Date
May 2008 (undefined)
Primary Completion Date
September 2010 (Actual)
Study Completion Date
September 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Unresectable or Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
71 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
FOLFIRI (The combination regimen of Irinotecan, l-Leucovorin and 5-Fluorouracil)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Sunitinib
Other Intervention Name(s)
Sutent
Intervention Description
37.5mg daily P.O., 4 weeks On 2weeks Off each 42 day cycle. Number of cycles: until progression or unacceptable toxicity develops.
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
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)
Secondary Outcome Measure Information:
Title
Overall Survival (OS)
Description
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)
Title
Percentage of Participants Who Presented Objective Response: Objective Response Rate (ORR)
Description
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)
Title
Duration of Response (DR)
Description
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)
Title
Maximum Observed Plasma Concentration (Cmax) and Predose Concentration (Ctrough) of Sunitinib.
Description
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
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Sunitinib
Time Frame
Cycle 1 Day 15
Title
Area Under the Plasma Concentration Versus Time Curve From Time 0 to 24 Hours Postdose (AUC 0-24) of Sunitinib
Description
AUC 0-24 was determined using the Linear/Log trapezoidal method.
Time Frame
Cycle 1 Day 15
Title
Apparent Oral Clearance (CL/F) of Sunitinib
Description
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
Title
Maximum Observed Plasma Concentration (Cmax) of Irinotecan
Description
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
Title
Time to Reach Maximum Plasma Concentration (Tmax) of Irinotecan
Time Frame
Cycle 1 Day 15
Title
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
Description
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
Title
Terminal Phase Elimination Half-life (t1/2) of Irinotecan
Description
Terminal phase half-life of irinotecan was calculated as ln 2/ kel.
Time Frame
Cycle 1 Day 15
Title
Clearance of Irinotecan
Description
CL is calculated as dose divided by AUC 0-∞
Time Frame
Cycle 1 Day 15
Title
Volume of Distribution at Steady State (Vss) of Irinotecan
Description
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
Title
Plasma Concentration at Steady State (Css) of 5-FU
Description
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
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Grade 3 or Higher Adverse Events According to Common Terminology Criteria (CTCAE).
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Pfizer Investigational Site
City
Nagoya
State/Province
Aichi
Country
Japan
Facility Name
Pfizer Investigational Site
City
Chiba-shi
State/Province
Chiba-ken
Country
Japan
Facility Name
Pfizer Investigational Site
City
Matsuyama-shi
State/Province
Ehime
Country
Japan
Facility Name
Pfizer Investigational Site
City
Sapporo-shi
State/Province
Hokkaido
Country
Japan
Facility Name
Pfizer Investigational Site
City
Sapporo
State/Province
Hokkaido
Country
Japan
Facility Name
Pfizer Investigational Site
City
Kochi-shi
State/Province
Kochi
Country
Japan
Facility Name
Pfizer Investigational Site
City
Saku
State/Province
Nagano
Country
Japan
Facility Name
Pfizer Investigational Site
City
Osakasayama-shi
State/Province
Osaka
Country
Japan
Facility Name
Pfizer Investigational Site
City
Takatsuki
State/Province
Osaka
Country
Japan
Facility Name
Pfizer Investigational Site
City
Shimotsuke-shi
State/Province
Tochigi
Country
Japan
Facility Name
Pfizer Investigational Site
City
Minoh/Osaka
Country
Japan
12. IPD Sharing Statement
Citations:
PubMed Identifier
22537162
Citation
Tsuji Y, Satoh T, Tsuji A, Muro K, Yoshida M, Nishina T, Nagase M, Komatsu Y, Kato T, Miyata Y, Mizutani N, Hashigaki S, Lechuga MJ, Denda T. First-line sunitinib plus FOLFIRI in Japanese patients with unresectable/metastatic colorectal cancer: a phase II study. Cancer Sci. 2012 Aug;103(8):1502-7. doi: 10.1111/j.1349-7006.2012.02320.x. Epub 2012 Jun 14.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A6181151&StudyName=Study%20Of%20Sunitinib%20With%20FOLFIRI%20In%20Colorectal%20Cancer
Description
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Learn more about this trial
Study Of Sunitinib With FOLFIRI In Colorectal Cancer
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