Table 9.
Clinical studies analyzing therapies targeting the cell cycle (CDK4/6), multifaceted pathways (proteasome, histone deacetylase, TGFβ) and DNA repair (PARP).
| Target | Molecule | Date | Protocol | Phase | Patients |
|---|---|---|---|---|---|
| CDK4/6 | Palbociclib (PD 0332991) | ||||
| NCT01227434 | 10/2010–07/2015 | Monotherapy combined or not combined to surgery | II | R | |
| Rb positif | |||||
| Results (22 patients): PFS 5.14 weeks; OS 15.4 weeks [252] | |||||
| 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 | |||||
| Abemaciclib | |||||
| NCT02981940 | 12/2016–03/2020 | Monotherapy combined or not combined to surgery | II | R | |
| Results: ongoing studies (no recruitment) | |||||
| Proteasome | Bortezomib | ||||
| NCT03643549 | 08/2018–02/2020 | Combined with TMZ | I/II | R | |
| MGMT unmethylated | |||||
| Results: ongoing studies (recruitment) | |||||
| NCT00641706 | 03/2008–05/2014 | Combined with vorinostat | II | R | |
| Results (37 patients): PFS 1.5 mois; OS 3.2 mois [253] | |||||
| NCT00998010 | 10/2009–05/2019 | Combined with TMZ/RT | II | N | |
| Unpublished data | |||||
| NCT00611325 | 02/2008–03/2014 | Combined with bevacizumab | II | R | |
| See Bevacizumab | |||||
| Marizomib | |||||
| NCT03345095 | 11/2017–06/2019 | Combined with TMZ/RT | III | N | |
| Results (749 patients): ongoing studies (recruitment) | |||||
| NCT03463265 | 08/2018–12/2020 | Monotherapy (ABI-009) or in combination with bevacuzimab or RT/TMZ or ABI-009, or lomustine | II | R/N | |
| See ABI-009 | |||||
| NCT02330562 | 01/2015–03/2020 | Combined with bevacuzimab | I/II | R | |
| See Bevacizumab | |||||
| Histone desacetylase | Vorinostat | ||||
| NCT00555399 | 11/2007–12/2019 | Combined with Isotretinoin and temozolomide | I/II | R | |
| Results: ongoing studies (no recruitment) | |||||
| NCT00731731 | 08/2008–03/2020 | Combined with TMZ/RT | II | N | |
| Preliminary results (107 patients): OS-15 months 54.6%; PFS 8.05 months | |||||
| NCT00238303 | 10/2005–05/2014 | Combined with surgery | II | R | |
| Results (68 patients): PFS 1.9 months; OS 5.7 months [254] | |||||
| NCT01110876 | 04/2010–11/2014 | Combined with erlotinib and TMZ | I/II | R | |
| See Erlotinib | |||||
| NCT00641706 | 03/2008–05/2014 | Combined with bortezomib | II | R | |
| See Bortezomib | |||||
| NCT01266031 | 12/2010–07/2018 | Bevacizumab in monotherapy vs. combined with vorinostat | I/II | R | |
| See Bevacizumab | |||||
| NCT01738646 | 11/2012–02/2017 | Combined with bevacizumab | II | R | |
| See Bevacizumab | |||||
| NCT00939991 | 07/2009–06/2013 | Combined with bevacizumab and TMZ | I/II | R | |
| See Bevacizumab | |||||
| Panobinostat (LBH589) | |||||
| NCT00848523 | 02/2009–07/2010 | Monotherapy | II | R | |
| Unpublished data | |||||
| FR901228 | |||||
| NCT00085540 | 06/2004–01/2017 | Monotherapy | I/II | R | |
| Results (35 patients): PFS 8 weeks [255] | |||||
| TGFβ & TGFβR | Trabedersen (AP12009) | ||||
| NCT00431561 | 02/2007–12/2013 | Monotherapy vs. TMZ or PVC (procarbazine/lomustine/vincristine) | IIb | R | |
| Results (145 patients): In GBM patients, response and survival results were comparable among the 3 arms [256] | |||||
| Galunisertib (LY2157299) | |||||
| NCT01582269 | 04/2012–12/2019 | Monotherapy or combined with lomustine | II | R | |
| Results: ongoing studies (no recruitment) | |||||
| NCT01220271 | 10/2010–02/2017 | Combined with TMZ/RT vs. TMZ/RT | I/II | N | |
| Results (56 patients): OS 18.2 vs. 17.9 months (HR = 1.2), PFS 7.6 vs. 11.5 months (HR = 1.8), patients treated with galunisertib combined with TMZ/RT vs. TMZ/RT [257] | |||||
| OKN-007 | |||||
| NCT03649464 | 08/2018–03/2020 | Monotherapy | I/II | R | |
| Not yet recruiting | |||||
| PARP | Iniparib (BSI-201) | ||||
| NCT00687765 | 06/2008–07/2015 | Combined with TMZ | I/II | N | |
| Results (81 patients): OS 22 months [258] | |||||
| Veliparib | |||||
| NCT02152982 | 06/2014–03/2020 | Combined with TMZ | II/III | N | |
| Results: ongoing studies (no recruitment) | |||||
| NCT03581292 | 07/2018–03/2020 | Combined with RT/TMZ | II | N | |
| Negative H3 K27M or BRAFV600 | |||||
| Results: ongoing studies (recruitment) | |||||
| NCT01026493 | 12/2009-/07/2017 | Combined with TMZ | I/II | R | |
| Results (215 patients): OS 10.3 vs. 10.7 months (p = 0.95; HR = 0.99) patients BEV-naïve low vs. high TMZ dose; OS 4.7 vs. 4.7 months (p = 0.93; HR = 0.93) patients BEV-failure low vs. high TMZ dose; PFS-6 17 vs. 4.4% patients BEV-naïve vs. BEV-failure [259] | |||||
| Olaparib | |||||
| NCT03212274 | 07/2017–03/2020 | Monotherapy | II | IDH1/2 mutations | |
| Results: ongoing studies (recruitment) | |||||
| NCT02974621 | 11/2016–03/2020 | Cediranib combined with olaparib and compared to bevacizumab | II | R | |
| See Cediranib | |||||
| Pamiparib | |||||
| NCT03150862 | 05/2017–11/2019 | Combined with RT/TMZ | I/II | R/N | |
| Results: ongoing studies (no recruitment) | |||||
| NCT03914742 | 04/2019-/2020 | Combined with TMZ | I/II | R IDH1/2 mutations | |
| 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.