Study Of Sunitinib With FOLFIRI In Colorectal Cancer

• ClinicalTrials.gov Identifier: NCT00668863
• Recruitment Status: Completed
• First Posted: April 29, 2008
• Results First Posted: October 7, 2011
• Last Update Posted: October 17, 2011
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: April 25, 2008
• First Posted Date: April 29, 2008
• Results First Submitted Date: September 2, 2011
• Results First Posted Date: October 7, 2011
• Last Update Posted Date: October 17, 2011
• Study Start Date: May 2008
• Actual Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 2, 2011)

Progression-Free Survival (PFS) [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: April 25, 2008): Progression-Free Survival (PFS) [ Time Frame: 12 months ]
• Change History: Complete list of historical versions of study NCT00668863 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: October 11, 2011)

• Overall Survival (OS) [ Time Frame: 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.
• Percentage of Participants Who Presented Objective Response: Objective Response Rate (ORR) [ Time Frame: 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) [ Time Frame: 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. [ Time Frame: 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 [ 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 [ Time Frame: Cycle 1 Day 15 ]
  AUC 0-24 was determined using the Linear/Log trapezoidal method.
• Apparent Oral Clearance (CL/F) of Sunitinib [ Time Frame: 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 [ Time Frame: 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.
• 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 [ Time Frame: 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 [ Time Frame: Cycle 1 Day 15 ]
  Terminal phase half-life of irinotecan was calculated as ln 2/ kel.
• Clearance of Irinotecan [ Time Frame: Cycle 1 Day 15 ]
  CL is calculated as dose divided by AUC 0-∞
• Volume of Distribution at Steady State (Vss) of Irinotecan [ Time Frame: 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 [ Time Frame: 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). [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: April 25, 2008)

• Objective response rate (ORR) and Duration of response (DR) [ Time Frame: 12 months ]
• Safety and Tolerability of sunitinib when administered in combination with FOLFIRI [ Time Frame: 12 months ]
• Plasma pharmacokinetics of sunitinib (and its metabolite SU012662), irinotecan (and its metabolite SN-38) and 5-FU [ Time Frame: 2 weeks ]
• Overall survival (OS) [ Time Frame: 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Unresectable or Metastatic Colorectal Cancer

Intervention

• Drug: FOLFIRI (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.
• Drug: Sunitinib
  37.5mg daily P.O., 4 weeks On 2weeks Off each 42 day cycle. Number of cycles: until progression or unacceptable toxicity develops.
  Other Name: Sutent

Study Arms

Experimental: 1

Interventions:

• Drug: FOLFIRI (The combination regimen of Irinotecan, l-Leucovorin and 5-Fluorouracil)
• Drug: Sunitinib

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 16, 2010): 71
• Original Estimated Enrollment (submitted: April 25, 2008): 70
• Actual Study Completion Date: September 2010
• Actual Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT00668863
• Other Study ID Numbers: A6181151
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Pfizer
• Study Sponsor: Pfizer
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: October 2011