Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors - Full Text View

Purpose

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.

Condition	Intervention	Phase
Colorectal Neoplasms Neoplasms	Drug: sunitinib + FOLFOX	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study Of SU011248 In Combination With Oxaliplatin, Leucovorin, And 5-Fluorouracil In Patients With Advanced Solid Malignancies

Resource links provided by NLM:

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Fluorouracil Malic acid Oxaliplatin Sunitinib malate Sunitinib

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: up to 20 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 ]
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 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 ]
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 ]
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 ]
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 ]
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 ]

Enrollment:	53
Study Start Date:	September 2005
Study Completion Date:	November 2008
Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	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

Arms

Assigned Interventions

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

Drug: sunitinib + FOLFOX

37.5 mg sunitinib + modified FOLFOX6 (Schedule 2/2)