Table 5.
Clinical studies analyzing therapies targeting mTOR, PI3K/mTOR, Akt & protein kinase c.
| Target | Molecule | Date | Protocol | Phase | Patients |
|---|---|---|---|---|---|
| mTOR | Temsirolimus | ||||
| NCT00800917 | 12/2008–01/2010 | Combined with bevacizumab | II | R | |
| Results (13 patients): PFS 8 weeks; OS 15 weeks [175] | |||||
| NCT00016328 | 05/2001–07/2013 | Monotherapy | II | R | |
| Results (65 patients): PFS 2.3 weeks; OS 4.4 months [176] | |||||
| NCT00329719 | 05/2006–10/2018 | Combined with sorafenib ± surgery | I/II | R | |
| Results (102 patients): PFS 2.71 vs. 4.34 vs. 1.87 months; OS 6.55 vs. 6.74 vs. 3.93 months. Temsirolimus + sorafenib vs. temsirolimus + sorafenib + surgery vs. temsirolimus + sorafenib in patients treated with anti-VEGF (No statistical data) [177] | |||||
| NCT01019434 | 11/2009–10/2016 | Combined with RT, compared with RT/TMZ | II | N. unmethylated MGMT | |
| Results (111 patients): PFS 5.4 months vs. 6.0 months (p = 0.24; HR = 1.26); OS 14.8 months vs. 16.0 months (p = 0.47; HR = 1.2) temsirolimus/RT vs. TMZ/RT [178] | |||||
| NCT00022724 | 01/2003–06/2018 | Monotherapy | I/II | R | |
| Results (43 patients): 9 weeks [179] | |||||
| NCT00112736 | 06/2005–06/2015 | Combined with erlotinib | I/II | R | |
| See Erlotinib | |||||
| NCT00335764 | 04/2006–07/2018 | Sorafenib combined with erlotinib, tipifarnib or temsirolimus | I/II | R | |
| See Sorafenib | |||||
| NCT03158389 | 05/2017–02/2020 | Molecularly Matched Targeted Therapies (APG101, alectinib, idasanutlin, atezolizumab, vismodegib, temsirolimus, palbociclib) combined with RT [71] | I/II | N without MGMT promoter methylation | |
| See Vismodegib | |||||
| Sirolimus | |||||
| NCT00672243 | 01/2008–02/2013 | Combined with erlotinib | II | R | |
| See Erlotinib | |||||
| Everolimus | |||||
| NCT00515086 | 08/2007–09/2011 | Monotherapy | II | R | |
| Unpublished data | |||||
| NCT00107237 | 04/2005–06/2013 | Combined with AEE788 (inhibitor of the EGFR, HER-2, VEGFR family) | II | R | |
| Unpublished data | |||||
| NCT01434602 | 09/2011–07/2017 | Combined with sorafenib | II | R | |
| Results: ongoing studies | |||||
| NCT00805961 | 12/2008–08/2013 | Combined with Bevacizumab in adjuvant therapy after RT/TMZ | II | N | |
| Results (68 patients): PFS 11.3 months; OS 13.9 months [180] | |||||
| NCT00553150 | 11/2007–02/2020 | Combination of RT/TMZ then TMZ/everolimus | II | N | |
| Results (100 patients): PFS-12 6.4 months; OS-12 15.8 months [181] | |||||
| NCT01062399 | 02/2010–05/2019 | Combined with RT/TMZ | I/II | N | |
| Results (171 patients): PFS: 8.2 vs. 10.2 months (p = 0.79); OS: 16.5 vs. 21.2 months (p = 0.008); Patients with or without everolimus [182] | |||||
| ABI-009 (nab-Rapamycin) | |||||
| NCT03463265 | 08/2018–12/2020 | Monotherapy or in combination with bevacuzimab or RT/TMZ or marizomib, or lomustine | II | R/N | |
| Results: ongoing studies (recruitment) | |||||
| PI3K | Pictilisib | ||||
| NCT02430363 | 03/2013–01/2016 | Monotherapy compared with pembrolizumab | I/II | R | |
| Unpublished data | |||||
| Buparlisib (BKM120) | |||||
| NCT01349660 | 04/2011–01/2017 | Combined with bevacizumab | I/II | R | |
| Preliminary data (76 patients): PFS 2.8 vs. 5.3 months; OS 6.5 vs. 10.8 months; buparlisib + bevacizumab vs. bevacizumab alone (No statistical data) | |||||
| NCT01339052 | 04/2011–03/2019 | Monotherapy combined or not combined with surgery | II | R | |
| Results (65 patients): PFS 1.7 months; OS 9.8 months; Patients not submitted to surgery [165] | |||||
| Sonolisib (PX-866) | |||||
| NCT01259869 | 04/2015–02/2015 | Monotherapy | II | R first | |
| Results (17 patients): PFS6 = 17% [183] | |||||
| Paxalisib (GDC-0084) | |||||
| NCT03522298 | 05/2018–03/2020 | Monotherapy | II | N | |
| Results: ongoing studies (no recruitment) | |||||
| PI3K/mTOR | Bimiralisib (PQR309) | ||||
| NCT02850744 | 08/2016–10/2018 | Monotherapy | II | N | |
| Unpublished data | |||||
| Akt & protein kinase c | Enzastaurin | ||||
| NCT00295815 | 02/2006–11/2016 | Compared with lomustine | III | R | |
| Results (293 patients): PFS 1.51 months vs. 1.64 months (p = 0.08; HR = 1.28); OS 6.60 months vs. 7.13 months (p = 0.25; HR = 1.20) enzastaurin vs. lomustine [184] | |||||
| NCT00509821 | 06/2007–04/2016 | Combined with RT (before, during, after) | II | N | |
| Results (60 patients): PFS 6.6 months; OS 15.0 months [185] | |||||
| NCT00402116 | 11/2006–10/2010 | Combined with the Stupp protocol | I/II | N | |
| Unpublished Phase II results | |||||
| NCT00586508 | 12/2007–10/2013 | Combined with bevacizumab | II | N | |
| Results (40 patients): PFS 2.0 months; OS = 7.5 months [186] | |||||
| NCT03776071 | 12/2018–05/2019 | Combined with RT/TMZ | II | N | |
| Results: ongoing studies (recruitment) | |||||
R: recurrent GBM; N: newly diagnosed GBM; PFS: progression-free survival; PFS-6: 6-month survival; OS: overall sur-vival. In red, not significant comparative tests. In italics, clinical trials listed in other tables (as mentioned). Results obtained from Clinicaltrials.com (accessed on 1 April 2020) and/or in cited references. Dates correspond to first posted and last update posted.