NCT01062399

Everolimus, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma Multiforme

Phase I/II Trial of Concurrent RAD001 (Everolimus) With Temozolomide/Radiation Followed by Adjuvant RAD001/Temozolomide in Newly Diagnosed Glioblastoma

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 279 (actual)
• Sponsor: Radiation Therapy Oncology Group · Network
• Sex: All
• Age: 18 Years – 120 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Brain and Central Nervous System Tumors

Interventions

Type	Name	Description
DRUG	concurrent RAD001 10 mg/day	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.
DRUG	concurrent temozolomide	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.
RADIATION	Radiation therapy	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.
DRUG	concurrent RAD001 2.5 mg/day	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.
DRUG	concurrent RAD001 5 mg/day	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.
DRUG	post-radiation RAD001 10 mg/day	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).
DRUG	post-radiation temozolomide	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)

Timeline

• Start date: 2010-12-01
• Primary completion: 2016-06-01
• Completion: 2022-05-20
• First posted: 2010-02-04
• Last updated: 2022-06-09
• Results posted: 2018-01-23

Locations

36 sites across 3 countries: United States, Canada, Israel