Back to resultsStudy Of Sunitinib Plus FOLFOX In Patients With Solid Tumors
Primary Purpose
Colorectal Neoplasms, Neoplasms
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
sunitinib + FOLFOX
sunitinib + FOLFOX
sunitinib + FOLFOX
sunitinib + FOLFOX
sunitinib + FOLFOX
sunitinib + FOLFOX
sunitinib + FOLFOX
Sponsored by
About this trial
This is an interventional treatment trial for Colorectal Neoplasms focused on measuring advanced solid tumors,, colorectal cancer,, sunitinib (SUTENT),, FOLFOX
Eligibility Criteria
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
Sites / Locations
- Pfizer Investigational Site
- Pfizer Investigational Site
- Pfizer Investigational Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Single arm
Arm Description
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
Outcomes
Primary Outcome Measures
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Secondary Outcome Measures
Objective Response (OR)
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 to Cmax (Tmax) of Sunitinib
Minimum Plasma Concentration (Cmin) of Sunitinib
Clearance (CL/F) of Sunitinib
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
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
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)
Tmax of SU-012662 (Sunitinib's Metabolite)
Cmin of SU-012662 (Sunitinib's Metabolite)
AUC24 for SU-012662 (Sunitinib's Metabolite)
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)
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)
t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel.
Cmax of Free Platinum
Oxaliplatin was metabolized to platinum and free platinum was measured.
Tmax of Free Platinum
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
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
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
Oxaliplatin was metabolized to platinum and total platinum was measured.
Tmax of Total Platinum
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
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)
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
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
Cmax of 5-FU
T1/2 of Free Platinum, Total Platinum, and 5-FU
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
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
Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)
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
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00599924
Brief Title
Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors
Official Title
Phase I Study Of SU011248 In Combination With Oxaliplatin, Leucovorin, And 5-Fluorouracil In Patients With Advanced Solid Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
September 2005 (undefined)
Primary Completion Date
November 2008 (Actual)
Study Completion Date
November 2008 (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
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.
Detailed Description
Study Design: Treatment, Single Group Assignment (7 cohorts), Open Label, Non-Randomized, Safety Study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Colorectal Neoplasms, Neoplasms
Keywords
advanced solid tumors,, colorectal cancer,, sunitinib (SUTENT),, FOLFOX
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
53 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Single arm
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
sunitinib + FOLFOX
Other Intervention Name(s)
Sunitinib malate, SUTENT, mFOLFOX6
Intervention Description
37.5 mg sunitinib + modified FOLFOX6 (Schedule 2/2)
Intervention Type
Drug
Intervention Name(s)
sunitinib + FOLFOX
Other Intervention Name(s)
Sunitinib malate, SUTENT, mFOLFOX6
Intervention Description
50 mg sunitinib + modified FOLFOX6 (Schedule 2/2)
Intervention Type
Drug
Intervention Name(s)
sunitinib + FOLFOX
Other Intervention Name(s)
Sunitinib malate, SUTENT, mFOLFOX6
Intervention Description
50 mg sunitinib + modified FOLFOX6 ( CRC, only Schedule 2/2)
Intervention Type
Drug
Intervention Name(s)
sunitinib + FOLFOX
Other Intervention Name(s)
Sunitinib malate, SUTENT, mFOLFOX6
Intervention Description
37.5 mg sunitinib + modified FOLFOX6 (Schedule 4/2)
Intervention Type
Drug
Intervention Name(s)
sunitinib + FOLFOX
Other Intervention Name(s)
Sunitinib malate, SUTENT, mFOLFOX6
Intervention Description
50 mg sunitinib + modified FOLFOX6 (Schedule 4/2)
Intervention Type
Drug
Intervention Name(s)
sunitinib + FOLFOX
Other Intervention Name(s)
Sunitinib malate, SUTENT, mFOLFOX6
Intervention Description
37.5 mg sunitinib + modified FOLFOX6 (Continuous Dosing)
Intervention Type
Drug
Intervention Name(s)
sunitinib + FOLFOX
Other Intervention Name(s)
Sunitinib malate, SUTENT, mFOLFOX6
Intervention Description
25 mg sunitinib + modified FOLFOX6 (Continuous Dosing)
Primary Outcome Measure Information:
Title
Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.
Time Frame
up to 20 weeks
Secondary Outcome Measure Information:
Title
Objective Response (OR)
Description
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.
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)
Title
Maximum Plasma Concentration (Cmax) of Sunitinib
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Time to Cmax (Tmax) of Sunitinib
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Minimum Plasma Concentration (Cmin) of Sunitinib
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Clearance (CL/F) of Sunitinib
Description
Drug clearance (CL/F) = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Area Under Plasma Concentration-Time Profile From Time Zero to Twenty-Four Hours Postdose (AUC24) of Sunitinib
Description
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.
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Terminal Phase Half-Life (t1/2) of Sunitinib
Description
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).
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Cmax of SU-012662 (Sunitinib's Metabolite)
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Tmax of SU-012662 (Sunitinib's Metabolite)
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Cmin of SU-012662 (Sunitinib's Metabolite)
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
AUC24 for SU-012662 (Sunitinib's Metabolite)
Description
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.
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose.
Title
CL/F of SU-012662 (Sunitinib's Metabolite)
Description
CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
T1/2 of SU-012662 (Sunitinib's Metabolite)
Description
t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel.
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Cmax of Free Platinum
Description
Oxaliplatin was metabolized to platinum and free platinum was measured.
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
Title
Tmax of Free Platinum
Description
Oxaliplatin was metabolized to platinum and free platinum was measured.
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
Title
Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) for Free Platinum
Description
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.
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
Title
T1/2 for Free Platinum
Description
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.
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
Title
Cmax of Total Platinum
Description
Oxaliplatin was metabolized to platinum and total platinum was measured.
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
Title
Tmax of Total Platinum
Description
Oxaliplatin was metabolized to platinum and total platinum was measured.
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
Title
Area Under the Plasma Concentration-Time Profile From Time Zero to Forty-Eight Hours (AUC48) for Total Platinum
Description
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.
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
Title
Steady State Concentration (Css) of Fluorouracil (5-FU)
Description
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.
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
Title
Steady State Clearance (CLss) of 5-FU
Description
CLss was determined by total amount of drug received during infusion or duration of infusion (Ki) divided by Css.
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
Title
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
Title
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
Title
T1/2 of Free Platinum, Total Platinum, and 5-FU
Description
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.
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
Title
CL/F of Free Platinum, Total Platinum, and 5-FU
Description
CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.
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
Title
Cmin of Free Platinum, Total Platinum, and 5-FU
Time Frame
pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
Title
Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)
Description
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).
Time Frame
Cycle 3 (Day 1), Cycle 3 (Day 8)
Title
Initial Area Dnder the Contrast Agent Concentration-Time Curve (IAUC) of Tumors in a Selected Group of Subjects Assessed by DCE-MRI
Description
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.
Time Frame
Cycle 3 (Day 1) and Cycle 3 (Day 8)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
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
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Pfizer Investigational Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
Pfizer Investigational Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
12. IPD Sharing Statement
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A6181048&StudyName=Study%20Of%20Sunitinib%20Plus%20FOLFOX%20In%20Patients%20With%20Solid%20Tumors
Description
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Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors
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