Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00599924
First received: January 11, 2008
Last updated: December 15, 2009
Last verified: December 2009
  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:


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

Detailed Description:

Study Design: Treatment, Single Group Assignment (7 cohorts), Open Label, Non-Randomized, Safety Study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00599924

Locations
United States, Colorado
Pfizer Investigational Site
Aurora, Colorado, United States, 80045
United States, Tennessee
Pfizer Investigational Site
Nashville, Tennessee, United States, 37232
United States, Texas
Pfizer Investigational Site
Dallas, Texas, United States, 75246
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer Inc
ClinicalTrials.gov Identifier: NCT00599924     History of Changes
Other Study ID Numbers: A6181048
Study First Received: January 11, 2008
Results First Received: November 4, 2009
Last Updated: December 15, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Pfizer:
advanced solid tumors,
colorectal cancer,
sunitinib (SUTENT),
FOLFOX

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Oxaliplatin
Sunitinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014