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Completed

NCT Number: NCT00599924

Study Of Sunitinib Plus FOLFOX In Patients With Solid Tumors

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.

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Key information

Conditions

Colorectal Neoplasms Colonic Diseases Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Pfizer Investigational Site, Aurora, Colorado, United States

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About this study

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

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

sunitinib + FOLFOX

Drug

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

Other names: Sunitinib malate, SUTENT, mFOLFOX6

Primary outcomes

  1. Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Time frame: up to 20 weeks

    All observed or volunteered AEs and SAEs regardless of treatment group or suspected causal relationship to the investigational product(s) were reported.

Secondary outcomes

  1. 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)

    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.

  2. Maximum Plasma Concentration (Cmax) of Sunitinib

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

  3. Time to Cmax (Tmax) of Sunitinib

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

  4. Minimum Plasma Concentration (Cmin) of Sunitinib

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

  5. Clearance (CL/F) of Sunitinib

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

    Drug clearance (CL/F) = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.

  6. 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

    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.

  7. Terminal Phase Half-Life (t1/2) of Sunitinib

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

    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).

  8. Cmax of SU-012662 (Sunitinib's Metabolite)

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

  9. Tmax of SU-012662 (Sunitinib's Metabolite)

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

  10. Cmin of SU-012662 (Sunitinib's Metabolite)

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

  11. AUC24 for SU-012662 (Sunitinib's Metabolite)

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose.

    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.

  12. CL/F of SU-012662 (Sunitinib's Metabolite)

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

    CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.

  13. T1/2 of SU-012662 (Sunitinib's Metabolite)

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

    t1/2 = terminal phase half-life. t1/2 was obtained by ln2 divided by kel.

  14. 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

    Oxaliplatin was metabolized to platinum and free platinum was measured.

  15. 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

    Oxaliplatin was metabolized to platinum and free platinum was measured.

  16. 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

    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.

  17. 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

    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.

  18. 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

    Oxaliplatin was metabolized to platinum and total platinum was measured.

  19. 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

    Oxaliplatin was metabolized to platinum and total platinum was measured.

  20. 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

    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.

  21. 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

    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.

  22. 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

    CLss was determined by total amount of drug received during infusion or duration of infusion (Ki) divided by Css.

  23. 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

  24. 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

  25. 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

    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.

  26. 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

    CL/F = dose divided by area under the plasma concentration-time profile from time zero to twenty-four hours.

  27. Cmin of Free Platinum, Total Platinum, and 5-FU

    Time frame: pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose

  28. 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)

    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).

  29. 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)

    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.

Sponsors and collaborators

Lead sponsor

Pfizer

Industry

Registry information

Official study title

Phase I Study Of SU011248 In Combination With Oxaliplatin, Leucovorin, And 5-Fluorouracil In Patients With Advanced Solid Malignancies

Important dates

Study start
2005
Primary completion
2008
Study completion
2008
First posted
Jan 24, 2008
Registry last updated
Jul 15, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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