Tipifarnib in Treating Patients With Recurrent or Progressive Malignant Glioma
Condition: Brain and Central Nervous System Tumors
MeSH terms: Glioma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Tipifarnib may stop the growth of tumor cells by blocking the enzymes necessary
      for tumor cell growth.

      PURPOSE: Phase II trial to study the effectiveness of tipifarnib in treating patients who
      have recurrent or progressive malignant glioma.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the maximum tolerated dose of tipifarnib in patients with recurrent or
           progressive malignant glioma receiving enzyme-inducing antiepileptic drugs. (Stratum II
           in the phase I portion of this study closed to accrual effective 07/16/2001.) (Phase I
           completed effective 10/2/2001.) (Phase II open only to patients requiring resection and
           who provide surgical tissue samples [effective 3/13/2003].)

        -  Define the safety and pharmacokinetic profile of this drug in this patient population.

        -  Assess for evidence of antitumor activity of this drug in these patients.

        -  Assess for evidence of inhibition of farnesyl protein transferase (FTase) on peripheral
           blood monocytes as a surrogate endpoint of effective biologic activity of this drug in
           these patients.

        -  Determine the efficacy of this drug as measured by 6-month progression-free survival and
           objective tumor response in these patients.

        -  Evaluate further the safety profile of this drug in these patients.

        -  Correlate treatment response with inhibition of FTase in peripheral blood monocytes in
           patients treated with this drug.

      OUTLINE: This is a dose-escalation, multicenter study. Patients are stratified according to
      their pretreatment medications (not receiving enzyme-inducing antiepileptic drugs [EIAEDs] vs
      receiving EIAEDs with or without steroids).

      Patients receive oral tipifarnib twice daily on days 1-21. Courses repeat every 4 weeks in
      the absence of unacceptable toxicity or disease progression.

        -  Phase I (completed 10/2/2001): Cohorts of 3-6 patients from stratum II receive
           escalating doses of tipifarnib until the maximum tolerated dose (MTD) is determined. The
           MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience
           dose-limiting toxicity. (Stratum II in the phase I portion of this study closed to
           accrual effective 07/16/2001.)

        -  Phase II (open only to patients requiring resection and who provide surgical tissue
           samples [effective 3/13/2003]): Once the MTD is determined, additional patients with
           glioblastoma multiforme from stratum II are accrued to receive treatment with tipifarnib
           at the recommended phase II dose.

      Patients are followed every 2 months for 1 year, every 3 months for 1 year, every 4 months
      for 1 year, and then every 6 months until progression. Patients are then followed every 4
      months thereafter.

      PROJECTED ACCRUAL: Approximately 30 patients (15 per stratum) will be accrued for the phase I
      portion of this study within 10 months. (Stratum II in the phase I portion of this study
      closed to accrual effective 07/16/2001.) (Phase I completed effective 10/2/2001.) A total of
      24 patients with glioblastoma multiforme from stratum II will be accrued for the phase II
      portion of this study. (Phase II open only to patients requiring resection and who provide
      surgical tissue samples [effective 3/13/2003].)
    

Intervention name(s): tipifarnib
Intervention type(s): Drug
Intervention MeSH terms: Tipifarnib
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: recurrent adult brain tumor; adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma