Everolimus and Gefitinib in Treating Patients With Progressive Glioblastoma Multiforme or Progressive Metastatic Prostate Cancer
Condition: Brain and Central Nervous System Tumors; Prostate Cancer
MeSH terms: Prostatic Neoplasms; Glioblastoma; Nervous System Neoplasms; Central Nervous System Neoplasms
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      RATIONALE: Everolimus may stop the growth of tumor cells by stopping blood flow to the tumor.
      Gefitinib may stop the growth of tumor cells by blocking the enzymes necessary for their
      growth. Combining everolimus with gefitinib may kill more tumor cells.

      PURPOSE: This phase I/II trial is studying the side effects and best dose of everolimus when
      given together with gefitinib and to see how well they work in treating patients with
      progressive glioblastoma multiforme or (progressive metastatic prostate cancer closed to
      accrual 10/19/06).
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  Determine the maximum tolerated dose of everolimus when given in combination with
           gefitinib in patients with progressive glioblastoma multiforme or (progressive castrate
           metastatic prostate cancer -closed to accrual as of 10/19/2006). (Phase I)

        -  Determine the safety and efficacy of this regimen in patients with progressive
           glioblastoma multiforme or (progressive castrate metastatic prostate cancer - closed to
           accrual as of 10/19/2006). (Phase II)

      Secondary

        -  Determine whether a pharmacokinetic interaction exists between everolimus and gefitinib
           in patients treated with this regimen.

        -  Determine the association between clinical outcomes and markers that may predict
           sensitivity of a tumor in patients treated with this regimen.

        -  Determine the pharmacodynamic effects of this regimen on post-therapy tumor specimens
           and peripheral blood mononuclear cells from these patients.

      OUTLINE: This is a phase I, open-label, non-randomized, dose-escalation study of everolimus
      followed by a phase II study.

        -  Phase I: Patients receive oral everolimus on day 1 and oral gefitinib once daily on days
           8-21. Beginning on day 22, patients receive oral everolimus once weekly and oral
           gefitinib once daily. Treatment with the combination continues in the absence of disease
           progression or unacceptable toxicity.

      Cohorts of 3-6 patients receive escalating doses of everolimus 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.

        -  Phase II (prostate cancer patients only) (closed to accrual as of 10/19/2006): Patients
           receive oral everolimus (at the MTD determined in phase I) once weekly and oral
           gefitinib once daily. Treatment continues in the absence of disease progression or
           unacceptable toxicity.
    

Intervention name(s): everolimus; gefitinib
Intervention type(s): Drug; Drug
Intervention MeSH terms: Everolimus; Gefitinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult glioblastoma; recurrent prostate cancer; recurrent adult brain tumor; stage IV prostate cancer; adult giant cell glioblastoma; adult gliosarcoma