Clinical trial NCT00599924: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Neoplasms
Neoplasms
Keywords: advanced solid tumors,
colorectal cancer,
sunitinib (SUTENT),
FOLFOX
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2008-01-24
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: up to 20 weeks
Secondary outcomes:
measure: Objective Response (OR)
timeFrame: 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)
measure: Maximum Plasma Concentration (Cmax) of Sunitinib
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Time to Cmax (Tmax) of Sunitinib
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Minimum Plasma Concentration (Cmin) of Sunitinib
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Clearance (CL/F) of Sunitinib
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Area Under Plasma Concentration-Time Profile From Time Zero to Twenty-Four Hours Postdose (AUC24) of Sunitinib
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Terminal Phase Half-Life (t1/2) of Sunitinib
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Cmax of SU-012662 (Sunitinib's Metabolite)
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Tmax of SU-012662 (Sunitinib's Metabolite)
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Cmin of SU-012662 (Sunitinib's Metabolite)
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: AUC24 for SU-012662 (Sunitinib's Metabolite)
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose.
measure: CL/F of SU-012662 (Sunitinib's Metabolite)
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: T1/2 of SU-012662 (Sunitinib's Metabolite)
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Cmax of Free Platinum
timeFrame: 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
measure: Tmax of Free Platinum
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to Infinity (AUCinf) for Free Platinum
timeFrame: 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
measure: T1/2 for Free Platinum
timeFrame: 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
measure: Cmax of Total Platinum
timeFrame: 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
measure: Tmax of Total Platinum
timeFrame: 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
measure: Area Under the Plasma Concentration-Time Profile From Time Zero to Forty-Eight Hours (AUC48) for Total Platinum
timeFrame: 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
measure: Steady State Concentration (Css) of Fluorouracil (5-FU)
timeFrame: 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
measure: Steady State Clearance (CLss) of 5-FU
timeFrame: 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
measure: Area Under the Curve (AUC) of 5-FU
timeFrame: 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
measure: Cmax of 5-FU
timeFrame: 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
measure: T1/2 of Free Platinum, Total Platinum, and 5-FU
timeFrame: 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
measure: CL/F of Free Platinum, Total Platinum, and 5-FU
timeFrame: 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
measure: Cmin of Free Platinum, Total Platinum, and 5-FU
timeFrame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose
measure: Volume Endothelial Transfer Constant (Ktrans) of Tumors in a Selected Group of Subjects Assessed by Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI)
timeFrame: Cycle 3 (Day 1), Cycle 3 (Day 8)
measure: Initial Area Dnder the Contrast Agent Concentration-Time Curve (IAUC) of Tumors in a Selected Group of Subjects Assessed by DCE-MRI
timeFrame: Cycle 3 (Day 1) and Cycle 3 (Day 8)
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Pfizer Investigational Site
state: Colorado
city: Nashville
country: United States
facility: Pfizer Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Pfizer Investigational Site
state: Texas
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: