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Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00599924
First received: January 11, 2008
Last updated: June 22, 2015
Last verified: June 2015

January 11, 2008
June 22, 2015
September 2005
November 2008   (final data collection date for primary outcome measure)
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: up to 20 weeks ] [ Designated as safety issue: Yes ]
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Type, incidence, severity, timing, seriousness, and relatedness of adverse events and laboratory abnormalities [ Time Frame: March 09 ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00599924 on ClinicalTrials.gov Archive Site
  • Objective Response (OR) [ Time Frame: From start of treatment until Day 8 of Cycles 4 and 8 (2/2 Schedule), Day 8 of Cycles 3 and 6 (4/2 Schedule), and Day 1 of Cycles 3 and 7 (Continuous Dosing) ] [ Designated as safety issue: No ]
    From the start of treatment until disease progression/recurrence. OR=confirmed Complete Response (CR) or confirmed Partial Response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST). CR = disappearance of all target lesions. CR was confirmed if it persisted on repeat imaging study ≥ 4 weeks after initial documentation of response. PR = ≥ 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. PR was confirmed if it persisted on repeat imaging study ≥ 4 weeks after initial documentation of response.
  • Maximum Plasma Concentration (Cmax) of Sunitinib [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Time to Cmax (Tmax) of Sunitinib [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Minimum Plasma Concentration (Cmin) of Sunitinib [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Clearance (CL/F) of Sunitinib [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    Drug clearance (CL/F) = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.
  • Area Under Plasma Concentration-Time Profile From Time Zero to Twenty-Four Hours Postdose (AUC24) of Sunitinib [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method.
  • Terminal Phase Half-Life (t1/2) of Sunitinib [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    t1/2 = terminal phase half-life. t1/2 was obtained by natural log of 2 (ln2) divided by the rate constant for terminal phase (kel).
  • Cmax of SU-012662 (Sunitinib's Metabolite) [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Tmax of SU-012662 (Sunitinib's Metabolite) [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Cmin of SU-012662 (Sunitinib's Metabolite) [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • AUC24 for SU-012662 (Sunitinib's Metabolite) [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose. ] [ Designated as safety issue: No ]
    AUC24 = Area under the plasma concentration-time profile from time zero (pre-dose) to twenty-four hours. AUC24 was obtained by the Linear/Log trapezoidal method.
  • CL/F of SU-012662 (Sunitinib's Metabolite) [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.
  • T1/2 of SU-012662 (Sunitinib's Metabolite) [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
    t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel.
  • Cmax of Free Platinum [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    Oxaliplatin was metabolized to platinum and free platinum was measured.
  • Tmax of Free Platinum [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    Oxaliplatin was metabolized to platinum and free platinum was measured.
  • Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) for Free Platinum [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    Oxaliplatin was metabolized to platinum and free platinum was measured. AUCinf = Area under the plasma concentration-time profile from time zero (pre-dose) to infinity. AUCinf was obtained by the Linear/Log trapezoidal method.
  • T1/2 for Free Platinum [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free platinum was measured.
  • Cmax of Total Platinum [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    Oxaliplatin was metabolized to platinum and total platinum was measured.
  • Tmax of Total Platinum [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    Oxaliplatin was metabolized to platinum and total platinum was measured.
  • Area Under the Plasma Concentration-Time Profile From Time Zero to Forty-Eight Hours (AUC48) for Total Platinum [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    Oxaliplatin was metabolized to platinum and total platinum was measured. AUC48 = Area under the plasma concentration-time profile from time zero (pre-dose) to forty-eight hours. AUC48 was obtained by the Linear/Log trapezoidal method.
  • Steady State Concentration (Css) of Fluorouracil (5-FU) [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    Steady state is reached when the amount of drug getting into the system per unit time is equal to the amount of drug cleared from the system.
  • Steady State Clearance (CLss) of 5-FU [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    CLss was determined by total amount of drug received during infusion or duration of infusion (Ki) divided by Css.
  • Area Under the Curve (AUC) of 5-FU [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
  • Cmax of 5-FU [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
  • T1/2 of Free Platinum, Total Platinum, and 5-FU [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel. Oxaliplatin was metabolized to platinum and free and total platinum were measured.
  • CL/F of Free Platinum, Total Platinum, and 5-FU [ Time Frame: pre-dose, 1h, 2h, 2 h 5 min, 2h 15 min, 2h 30 min, 2h 45 min, 4h, 6h, 8h, 10h, 24h, and 48h post-dose ] [ Designated as safety issue: No ]
    CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.
  • Cmin of Free Platinum, Total Platinum, and 5-FU [ Time Frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose ] [ Designated as safety issue: No ]
  • Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) [ Time Frame: Cycle 3 (Day 1), Cycle 3 (Day 8) ] [ Designated as safety issue: No ]
    Volume endothelial Ktrans was estimated by fitting the tissue contrast agent time course to the Kety equation (Tofts model for analysis of DCE-MRI data).
  • Initial Area Dnder the Contrast Agent Concentration-Time Curve (IAUC) of Tumors in a Selected Group of Subjects Assessed by DCE-MRI [ Time Frame: Cycle 3 (Day 1) and Cycle 3 (Day 8) ] [ Designated as safety issue: No ]
    IAUC: The initial area under the curve was estimated by integrating the area under the contrast agent concentration time course for the first 90 seconds after bolus arrival in the tumor.
  • Pharmacokinetic parameters of SU011248 (and its active metabolite, SU012662), oxaliplatin, and 5-FU [ Time Frame: March 09 ] [ Designated as safety issue: Yes ]
  • Objective disease response [ Time Frame: March 09 ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors
Phase I Study Of SU011248 In Combination With Oxaliplatin, Leucovorin, And 5-Fluorouracil In Patients With Advanced Solid Malignancies
This study determined the maximum tolerated dose and safety of SU011248 (sunitinib malate, SUTENT) in combination with FOLFOX [Leucovorin + Fluorouracil (5-FU) + Oxaliplatin]. Three different dosing regimens with starting doses of sunitinib at 37.5 mg/day (Schedule 2/2, Schedule 4/2, and Continuous Dosing) were tested in patients with advanced solid tumors, including colorectal cancer.
Study Design: Treatment, Single Group Assignment (7 cohorts), Open Label, Non-Randomized, Safety Study.
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Colorectal Neoplasms
  • Neoplasms
  • Drug: sunitinib + FOLFOX
    37.5 mg sunitinib + modified FOLFOX6 (Schedule 2/2)
    Other Name: Sunitinib malate, SUTENT, mFOLFOX6
  • Drug: sunitinib + FOLFOX
    50 mg sunitinib + modified FOLFOX6 (Schedule 2/2)
    Other Name: Sunitinib malate, SUTENT, mFOLFOX6
  • Drug: sunitinib + FOLFOX
    50 mg sunitinib + modified FOLFOX6 ( CRC, only Schedule 2/2)
    Other Name: Sunitinib malate, SUTENT, mFOLFOX6
  • Drug: sunitinib + FOLFOX
    37.5 mg sunitinib + modified FOLFOX6 (Schedule 4/2)
    Other Name: Sunitinib malate, SUTENT, mFOLFOX6
  • Drug: sunitinib + FOLFOX
    50 mg sunitinib + modified FOLFOX6 (Schedule 4/2)
    Other Name: Sunitinib malate, SUTENT, mFOLFOX6
  • Drug: sunitinib + FOLFOX
    37.5 mg sunitinib + modified FOLFOX6 (Continuous Dosing)
    Other Name: Sunitinib malate, SUTENT, mFOLFOX6
  • Drug: sunitinib + FOLFOX
    25 mg sunitinib + modified FOLFOX6 (Continuous Dosing)
    Other Name: Sunitinib malate, SUTENT, mFOLFOX6
Experimental: Single arm

SU011248 [sunitinib] in combination with FOLFOX; FOLFOX is a chemotherapy regimen that combines oxaliplatin and leucovorin with bolus and infusion 5-FU. The modified FOLFOX 6 (mFOLFOX6) regimen is one of several different regimens of FOLFOX used in clinic, according to different dosages of the 4 drugs. mFOLFOX6 was administered every 2 weeks on Days 1 and 2 of each cycle.

25, 37.5 and 50 mg/day, oral, administered on an outpatient basis in three different dosing regimens: schedule 2/2 (2 weeks on, 2 weeks off), schedule 4/2 (4 weeks on, 2 weeks off), and continuous daily dosing (every day); FOLFOX will be administered every 2 weeks, using the modified FOLFOX 6 (mFOLFOX6) regimen, consisting of: oxaliplatin 85 mg/m2 + leucovorin 400 mg/m2 as a 2-hr IV infusion; 5-FU 400 mg/m2 IV bolus, followed by - 5-FU 2400 mg/m2 as a 46-hr IV infusion

Interventions:
  • Drug: sunitinib + FOLFOX
  • Drug: sunitinib + FOLFOX
  • Drug: sunitinib + FOLFOX
  • Drug: sunitinib + FOLFOX
  • Drug: sunitinib + FOLFOX
  • Drug: sunitinib + FOLFOX
  • Drug: sunitinib + FOLFOX
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
53
November 2008
November 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Advanced solid tumor malignancy (during expansion at the maximum tolerated dose, entry will be limited to patients wtih adenocarcinoma of the colon or rectum)
  • Eastern Cooperative Oncology Group (ECOG) 0 or 1

Exclusion Criteria:

  • Prior treatment with more than 6 cycles of traditional alkylating agent-based chemotherapy regimens
  • Prior treatment with more than 2 cycles of carboplating-based chemotherapy regimens
  • For colorectal cancer patients in the expanded cohorts, prior treatment with more than 2 systemic chemotherapy regimens in the metastatic setting
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00599924
A6181048
No
Not Provided
Not Provided
Pfizer
Pfizer
Not Provided
Study Director: Pfizer CT.gov Call Center Pfizer
Pfizer
June 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP