Study Of Sunitinib With FOLFIRI In Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00668863
First received: April 25, 2008
Last updated: October 11, 2011
Last verified: October 2011
  Purpose

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


Condition Intervention Phase
Unresectable or Metastatic Colorectal Cancer
Drug: FOLFIRI (The combination regimen of Irinotecan, l-Leucovorin and 5-Fluorouracil)
Drug: Sunitinib
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Up to 11 cycles (1 cycle = 6 weeks) ] [ Designated as safety issue: No ]

    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) [ Time Frame: Up to 11 cycles (1 cycle = 6 weeks) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
    AUC 0-24 was determined using the Linear/Log trapezoidal method.

  • Apparent Oral Clearance (CL/F) of Sunitinib [ Time Frame: Cycle 1 Day 15 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]
    Terminal phase half-life of irinotecan was calculated as ln 2/ kel.

  • Clearance of Irinotecan [ Time Frame: Cycle 1 Day 15 ] [ Designated as safety issue: No ]
    CL is calculated as dose divided by AUC 0-∞

  • Volume of Distribution at Steady State (Vss) of Irinotecan [ Time Frame: Cycle 1 Day 15 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 71
Study Start Date: May 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00668863

Locations
Japan
Pfizer Investigational Site
Nagoya, Aichi, Japan
Pfizer Investigational Site
Chiba-shi, Chiba-ken, Japan
Pfizer Investigational Site
Matsuyama-shi, Ehime, Japan
Pfizer Investigational Site
Sapporo, Hokkaido, Japan
Pfizer Investigational Site
Sapporo-shi, Hokkaido, Japan
Pfizer Investigational Site
Kochi-shi, 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
Pfizer Investigational Site
Minoh/Osaka, Japan
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided by Pfizer

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT00668863     History of Changes
Other Study ID Numbers: A6181151
Study First Received: April 25, 2008
Results First Received: September 2, 2011
Last Updated: October 11, 2011
Health Authority: Japan: Ministry of Health, Labor and Welfare

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Irinotecan
Sunitinib
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Antidotes

ClinicalTrials.gov processed this record on April 17, 2014