Table 1.
Summary of Malignant Glioma Clinical Trials with Pharmacological Agents that Target the Ras Pathway
| Agent | Targets | Phase | Study Design | Outcomes | Trial ID and References |
|---|---|---|---|---|---|
| Completed Trials | |||||
| Lonafarnib (SCH 66336/ Sarasar) |
FTase | I | single agent 53 children with brain tumors |
Recommendations for phase-2 doses | Pediatric Brain Tumor Consortium Study Kieran 2007 [80] |
| Tipifarnib (R115777/ Zarnestra) |
FTase | II | single agent 67 recurrent GBM 22 recurrent AA |
6-month PFS: 9% in AA 12% in GBM |
North American Brain Tumor Consortium Study Cloughesy 2006 [81] |
| Perillyl alcohol | FTase 37 recurrent AA, GBM &AO |
I/II | single agent | 6-month PFS: 48.2% in GBM 60% in AA 66.6% in AO |
Brazilian trials de Fonseca 2008 [87] |
| Sorafenib (BAY 43-9006/ Nexavar) |
RAF-1 PDGFR VEGFR |
I | single agent 35 recurrent AA, GBM &AO |
MTD determined | NABTT 0401 Nabors 20073 |
| I/II | sorafenib+ sirolimus (mTOR inhibitor) 32 recurrent GBM phase I: 13 recurrent GBM phase II: 19 recurrent GBM |
6-month PFS: 0% | NABTC 05–02 Wen 20095 |
||
| I/II | sorafenib+ erlotinib (EGFR inhibitor) phase I: 17 recurrent GBM phase II: 19 recurrent GBM |
sorafenib altering erlotinib metabolism or clearancephase II outcome to be prepared |
NABTC 05–02 Prados 20091 |
||
| II | radiation+TMZ+ sorafenib 45 GBM |
median PFS: 6 months | Lamar 20093 | ||
| Ongoing Trials | |||||
| Sorafenib PDGFR VEGFR |
RAF-1 | I | single agent recurrent AA & GBM |
NCT00093613 | |
| I | radiation+TMZ+sorafenib first-line treatment for AA & GBM |
NCT00884416 | |||
| II | TMZ+sorafenib recurrent AA & GBM |
NCT00597493 | |||
| I/II | radiation+TMZ+sorafenib 4 study arms newly diagnosed GBM & gliosarcoma |
NCT00734526 | |||
| II | radiation+TMZ+sorafenib first-line treatment for GBM |
NCT00544817 | |||
| I/II | sorefenib+temsirolimus (mTOR inhibitor) recurrent GBM |
NCT00329719 | |||
| II | sorefenib+ bevacizumab/Avastin (VEGF antibody) recurrent GBM |
NCT00621686 | |||
| Tipifarnib Sorafenib |
FTase RAF-1 PDGFR VEGFR |
I/II | Arm 1: sorefenib+erlotinib (EGFR inhibitor) Arm 2: sorefenib+temsirolimus (mTOR inhibitor) Arm 3: sorefenib+tipifarnib recurrent GBM & gliosarcoma |
NCT00335764 | |
PFS: progression-free survival, MTD: maximum tolerance dose, AO: anaplastic oligodendrogliomas, TMZ: temozolomide.