Clinical Trial: Sunitinib in Treating Patients With Recurrent Malignant Gliomas

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Pharmacokinetic and Phase 2 Study of Sunitinib Malate in Recurrent Malignant Gliomas

Brief Summary: This phase II trial is studying how well sunitinib works in treating patients with recurrent malignant gliomas. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the efficacy of sunitinib malate in patients with recurrent malignant gliomas as measured by 6-month progression-free survival.

II. To determine the lower of the dose of sunitinib malate in patients receiving enzyme-inducing anti-convulsants that would achieve similar serum drug and metabolite concentrations as that in patients not receiving enzyme-inducing anticonvulsants or the maximum tolerated dose in the same population.

SECONDARY OBJECTIVES:

I. To examine the toxicity and safety of sunitinib malate in patients with the above noted tumors.

II. To evaluate tumor responses in the stated patients. III. To evaluate progression-free and overall survival in the stated patients.

OUTLINE: This is a multicenter study. Patients are stratified according to use of enzyme-inducing anticonvulsants (EIAC) (yes vs no).

STRATUM 1 (non-EIAC): Patients receive oral sunitinib malate once daily for 4 consecutive weeks followed by 2 weeks of rest.

STRATUM 2 (EIAC & OSU patients only): Patients receive oral sunitinib malate as in stratum 1. Patients receive escalating doses of oral sunitinib malate until the maximum tolerated dose (MTD) is determined.

Patients undergo blood sample collection periodically for pharmacokinetic studies. Samples are analyzed for plasma concentrations of sunitinib malate via LC/MS/MS method.

In both strata, treatment repeats every 6 weeks in the absence of disease progression or unacc
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Progression-free Survival at 6 Months (Stratum 1) [ Time Frame: From time to registration to up to 6 months ]
    Number of patients with Progression-free Survival at 6 months for Stratum 1
  • Maximum Tolerable Dose Based on Dose-limiting Toxicity of Sunitinib in Patients Receiving EIAC (Stratum 2) [ Time Frame: From the time of first treatment with sunitinib until completion of treatment, assessed up to 30 days ]
    Maximum tolerable dose of sunitinib in patients receiving treatment with EIAC agents using dose escalation based on the steady-state trough sunitinib + SU12662 plasma concentrations on day 14 observed in patients treated in stratum 1. Six patients will be treated in each dose cohort with up to 12 patients being treated at the maximum tolerable dose for a total of 18-24 patients with gliomas receiving EIAC.
  • Dose Resulting in Steady-state Trough [ Time Frame: At baseline (day 8) and days 15, 22, and 23 ]
    Average of pre-dose values of sunitinib + SU12662 plasma concentrations equivalent to that observed in patients not receiving EIAC based on pharmacokinetic modeling.


Original Primary Outcome:

  • Progression-free survival at 6 months
  • Maximum tolerable dose
  • Biologically active dose


Current Secondary Outcome:

  • Confirmed Objective Response (Complete Response[CR] or Partial Response [PR]) [ Time Frame: up to 12 weeks ]
    Confirmatory scans should also be obtained within 4 to 6 weeks following initial documentation of objective response. Confidence intervals for the true proportion will be calculated using the exact binomial method. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
  • Percentage of Patients Progression Free at 12 Months [ Time Frame: At 12 months after the start of treatment ]
  • Overall Survival [ Time Frame: up to 12 months ]


Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: July 10, 2007
Date Started: June 2007
Date Completion:
Last Updated: January 29, 2016
Last Verified: January 2016