Clinical Trial: Tandutinib in Treating Patients With Recurrent or Progressive Glioblastoma

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

Official Title: A Feasibility Assessment and a Phase I/II Trial of MLN518 for Treatment of Patients With Recurrent Glioblastoma

Brief Summary: This phase I/II trial is studying the side effects and best dose of tandutinib and to see how well it works in treating patients with recurrent or progressive glioblastoma.Tandutinib 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. Assess the ability of tandutinib to achieve a target tumor/plasma ratio ≥ 0.33 in patients with recurrent glioblastoma undergoing resection. (Feasibility study) II. Detect potential biological effects of tandutinib by measuring platelet-derived growth factor receptor phosphorylation status and downstream activation of Akt and Erk. (Feasibility study) III. Determine the maximum tolerated dose of tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) IV. Estimate the frequency of toxicities associated with tandutinib in patients with recurrent or progressive glioblastoma. (Phase I) V. Describe the pharmacokinetics of this route of administration in patients with recurrent or progressive glioblastoma. (Phase I) VI. Assess tumor response rate in patients with recurrent or progressive glioblastoma. (Phase II)

SECONDARY OBJECTIVES:

I. Estimate overall survival of patients with recurrent or progressive glioblastoma. (Phase II) II. Estimate the 6-month progression-free survival rate in these patients. (Phase II) III. Assess the toxicities associated with tandutinib in these patients. (Phase II) IV. Assess the pharmacokinetic profile of this route of administration in these patients. (Phase II) V. Explore protein-expression patterns that distinguish patients who respond to therapy from those who do not. (Phase II)

OUTLINE: This is a multicenter, prospective, nonrandomized, feasibility study and phase I study (in parallel) followed by an open label phase II study.

FEASIBILITY STUDY: Patients receive oral tandutinib twice daily for 7 days. Patients then undergo biopsy or surgery to remove the tumor. Within 2 weeks after biopsy or surger
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Maximum Tolerated Dose of Tandutinib Defined by Dose Limiting Toxicities (Phase 1) [ Time Frame: cycle 1 - 28 days ]
  • To Determine the Tumor/Plasma Ratio of in Subjects With Recurrent GBM Undergoing Resections (Phase 0) [ Time Frame: 7 days prior to surgery including surgery ]
    participants are administered tandutinib (500mg BID) for 7 days prior to surgery and then undergo resection for recurrent glioblastoma. Tissue samples will be collected for correlative studies - determine tumor/plasma ratio.
  • Number of Dose Limiting Toxicities Per Dose Level [ Time Frame: 28 days ]

    cohorts of 3-6 pts will recieve oral tandutinib starting at 500mg BID with a dose escalation in each cohort. Each treatment cycle is 28 days. Evaluation period for MTD is 1st cycle - 28 days.

    dose limiting toxicity defined as: grades 3-4 severity (except vomiting and diarrhea without sufficient prophylaxis delay of treatment > 14 days. ANC less/equal 500m/mm3; Plts less/equal 25,000/mm3; febrile neutropenia or delay of treatment > 14 days

  • Tumor Response (Complete Response and Partial Response) Rate (Phase II) [ Time Frame: Up to 4 years ]

    pts receive a scan baseline and prior to every odd cycle. All responses are centrally reviewed Complete response Complete disappearance of all tumor on MRI scan, off all glucocorticoids with stable or improving neurological exam minimum of 4 wks Partial response Greater than or equal 50% reduction in tumor size on MRI, on sab

    Original Primary Outcome:

    Current Secondary Outcome:

    • Overall Survival (Phase II) [ Time Frame: Up to 4 years ]
      Median time of survival along with 95% confidence interval will be estimated using Kaplan-Meier method. An overall failure rate will be estimated with 95% CI.
    • Six-month Progression-free Survival Rate (Phase II) [ Time Frame: At 6 months ]

      The probability of 6-momth progression-free survival will be estimated using binomial distribution.

      Progression defined as: Progressive neurological abnormalities not explained by other causes or greater than 25% increase in size of tumor or if new lesion.

    • Overall Failure Rate (Phase II) [ Time Frame: up to 4 years ]
      The overall failure rate is expressed as hazard of failure per person-year of follow-up.
    • Proportion of Patients With Serious or Life Threatening Toxicities [ Time Frame: 2 year period ]
      Grade 3 or 4 toxicities related to treatment as determined by the CTCAE
    • Protein Expression Patterns Post Treatment - Loss or Gain [ Time Frame: baseline - cycle 2 (28 days) ]

      serial blood samples over multiple time points (prior to treatment, 2 days post treatment, 8 days post treatment, 10 days post treatment and 28 days post treatment.

      statistical analyses presented for the comparisons that yielded a p-value <=0.05



    Original Secondary Outcome:

    Information By: National Cancer Institute (NCI)

    Dates:
    Date Received: September 19, 2006
    Date Started: January 2007
    Date Completion:
    Last Updated: February 22, 2017
    Last Verified: February 2017