Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Condition: Brain and Central Nervous System Tumors
MeSH terms: 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 blocking some of the enzymes
      needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy,
      such as temozolomide, work in different ways to stop the growth of tumor cells, either by
      killing the cells or by stopping them from dividing. Radiation therapy uses high energy
      x-rays to kill tumor cells. Giving everolimus together with temozolomide and radiation
      therapy 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 temozolomide and radiation therapy and to see how well it works in
      treating patients with newly diagnosed glioblastoma multiforme.
    

Detailed description: 
      OBJECTIVES:

      Primary

        -  To define the maximum tolerated dose of everolimus (up to an established dose of 10
           mg/day) when combined with concurrent radiotherapy and temozolomide in patients with
           newly diagnosed glioblastoma multiforme. (Phase I)

        -  To determine the efficacy of everolimus in combination with radiotherapy and
           temozolomide followed by adjuvant everolimus in combination with temozolomide, as
           measured by progression-free survival, in these patients. (Phase II)

      Secondary

        -  To characterize the safety profile of everolimus in combination with radiotherapy and
           temozolomide in these patients. (Phase I)

        -  To determine the overall survival of these patients. (Phase II)

        -  To further evaluate the safety profile of everolimus in combination with radiotherapy
           and temozolomide in these patients. (Phase II)

        -  To determine if activation of the Akt/mTOR axis predicts response to everolimus. (Phase
           II)

        -  To determine if there is an association between tumor MGMT gene methylation status and
           response to everolimus. (Phase II)

      OUTLINE: This is a multicenter, phase I, dose-escalation study of everolimus followed by a
      phase II, randomized study.

      After completion of study treatment, patients are followed up every 3 months for 1 year,
      every 4 months for 1 year, and then every 6 months thereafter.
    

Intervention name(s): concurrent RAD001 10 mg/day; concurrent temozolomide; Radiation therapy; concurrent RAD001 2.5 mg/day; concurrent RAD001 5 mg/day; post-radiation RAD001 10 mg/day; post-radiation temozolomide
Intervention type(s): Drug; Drug; Radiation; Drug; Drug; Drug; Drug
Intervention description(s): During radiation: RAD001 10 mg orally daily during radiation therapy; one hour prior to radiation and in the morning on weekends on days 1-42.; During radiation: temozolomide 75 mg/m2/day orally daily during radiation therapy; one hour prior to radiation and in the morning on weekends on days 1-42. Dose rounded to the nearest 5 mg.; Intensity Modulated RT (IMRT) allowed. For both IMRT and 3D conformal radiotherapy (3D-CRT) plans, one treatment of 2 Gy given daily 5 days per week for a total of 60 Gy over 6 weeks.; During radiation: RAD001 2.5 mg orally daily during radiation therapy; one hour prior to radiation and in the morning on weekends on days 1-42.; During radiation: RAD001 5 mg orally daily during radiation therapy; one hour prior to radiation and in the morning on weekends on days 1-42.; Post-radiation: RAD001 10 mg orally daily on days 1-28 of each cycle, for up to 12 cycles, starting 28 days after the completion of radiation therapy (Cycle = 28 days).; Post-radiation: temozolomide 150 mg/m2/day - 200 mg/m2/day orally daily on days 1-5 of each cycle, starting 28 days after the completion of radiation therapy for up to 12 cycles (Cycle = 28 days)
Other intervention name(s): everolimus; everolimus; everolimus; everolimus
Intervention MeSH terms: Everolimus; Temozolomide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: adult glioblastoma; adult giant cell glioblastoma; adult gliosarcoma