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
  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 ]
    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) [ 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.


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: Pfizer
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: June 22, 2015
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on August 27, 2015