. 2021 Apr 9;13(8):1795. doi: 10.3390/cancers13081795

Table 10.

Clinical studies analyzing therapies targeting VEGF and VEGFR.

Target	Molecule	Date	Protocol	Phase	Patients
VEGF	Bevacizumab
	NCT01609790	06/2012–03/2020	Combined with trebananib	II	R
	Preliminary results (116 patients): OS 11.5 vs. 7.5 months (p = 0.09; HR = 1.46); PFS 4.8 vs. 4.2% (p = 0.04; HR = 1.51)
	NCT00817284	01/2009–11/2011	Combined with RT/TMZ or RT/irinotecan	II	N
	Unpublished data
	NCT01860638	05/2013–04/2018	Continuous treatment with Stupp, followed with Lomustine in first disease progression (PD1) and with chemotherapy in second progression (PD2)	II	R
	Results (296 patients): OS 6.4 vs. 5.5 months (HR = 1.04); PFS 2.3 vs. 1.8 months (HR = 0.70) PD1 lomustine bevacizumab vs. lomustine alone; PFS 2 vs. 2.2 months (HR = 0.70) PD2 bevacizumab chemotherapy vs. chemotherapy alone. No p values were reported [278]
	NCT01115491	05/2010–12/2014	Combined with TMZ	II	R
	Results (32 patients): PFS 18.29 weeks; OS 31.43 weeks
	NCT00590681	01/2008–09/2015	Combined with TMZ	II	N
	Unpublished data
	NCT00979017	09/2009–03/2014	Combined with TMZ and irinotecan	II	N unresectable and multifocal
	Results (41 patients): OS 12 months; PFS 8.6 months [279]
	NCT01186406	08/2010–02/2019	Combined with gliadel, TMZ and RT	II	N
	Results (41 patients): OS 19.4 months; PFS 11.3 months
	NCT01903330	07/2013–11/2019	Combined with ERC1671 (vaccine) and granulocyte-macrophage colony-stimulating factor (GM-CSF) compared to combination with placebo	II	R
	Results: ongoing studies (recruitment)
	NCT01443676	09/2011–11/2016	Combined with RT compared to RT alone	II	N in elderly
	Results (75 patients): PFS 7.6 vs. 4.8 months (p = 0.003); OS 12.1 vs. 12.2 months (p = 0.77); bevacizumab + RT vs. RT [280]
	NCT02898012	09/2016–09/2016	Combined with TMZ	II	N age over 70
	Results (66 patients): OS 23.9 weeks; PFS 15.3 weeks [281]
	NCT01149850	06/2010–02/2020	Combined with TMZ	II	N in elderly
	Results: ongoing studies (no recruitment)
	NCT01004874	10/2009–02/2020	Combined with RT/TMZ followed by combination with TMZ/popotecan	II	/
	Preliminary results (80 patients): OS 17.2 months; PFS 11.1 months
	NCT00735436	08/2008–02/2013	Combined with gliadel and irinotecan	II	N
	Results (18 patients): PFS 8 months; OS 13.5 months
	NCT02698280	03/2016–07/2018	Combined with nimustine	II	R
	Unpublished data
	NCT01266031	12/2010–07/2018	Monotherapy vs. combined with vorinostat	I/II	R
	Results (patients): OS 9.24 vs. 7.8 months; bevacizumab vs. bevacizumab + vorinostat
	NCT01013285	11/2009–01/2016	Combined with TMZ and RT	II	N
	Results: ongoing studies (recruitment unknown)
	NCT01738646	11/2012–02/2017	Combined with vorinostat	II	R
	Results (38 patients): PFS 3.7 months; OS 10.4 months; PFS-6 30% [282]
	NCT00939991	07/2009–06/2013	Combined with vorinostat and TMZ	I/II	R
	Results (39 patients): PFS 6.7 months; OS 12.5 months; PFS-6 53.8%
	NCT00337207	06/2006–02/2020	Monotherapy	II	R
	Results (54 patients): PFS-6 24%
	NCT00268359	12/2005–07/2014	Combined with irinotecan	II	R
	Results (32 patients): PFS 23 weeks; PFS-6 38% OS-6 72% [283]
	NCT00795665	11/2008–03/2020	Combined with carmustine	II	R
	Unpublished data
	NCT02330562	01/2015–03/2020	Combined with marizomib	I/II	R
	Results: ongoing studies (no recruitment)
	NCT00921167	06/2009–12/2013	Combined with irinotecan	II	R
	Results: completed, no results posted
	NCT02157103	06/2014–05/2018	Subcutaneous monotherapy	II	R
	Results (3 patients): 66.7% decrease in radiation-related edema
	NCT01209442	09/2010–04/2019	Combined with hypofractionated RT and TMZ	II	N
	Results (30 patients): PFS 14.3 months; OS 16.3 months [284]
	NCT02120287	04/2014–05/2019	Combined with radiosurgery	II	R
	Results (16 patients): OS 11.73 months
	NCT01102595	04/2010–08/2015	Combined with TMZ in neoadjuvant therapy of the Stupp protocol compared to the Stupp protocol	II	N, unresectable
	Results (102 patients): PFS 2.2 vs. 4.8 months (p = 0.10; HR = 0.70); OS 7.7 vs. 10.6 months (p = 0.07; HR = 0.68); TMZ vs. TMZ + bevacizumab [285]
	NCT01022918	12/2009–09/2012	Combined with irinotecan in neoadjuvant and adjuvant therapy with TMZ, compared to neoadjuvant TMZ and Stupp	II	N, unresectable
	Results: (120 patients): PFS = 7.1 vs. 5.2 months (HR = 0.82); OS = 11.1 vs. 11.1 months; bevacizumab/Irinotecan vs. ctrl [286]
	NCT00943826	07/2009–09/2017	Combined with TMZ during the Stupp protocol, compared to the Stupp protocol	III	N
	Results (921 patients): PFS 10.6 vs. 6.2 months (p < 0.001; HR = 0.64); OS 16.8 vs. 16.7 months (p = 0.1; HR = 0.88); bevacizumab + Stupp vs. Stupp [287]
	NCT01067469	02/2010–03/2020	Low dose and combined with lomustine, compared to high dose bevacizumab alone	II	R
	Results (69 patients): PFS 4.34 vs. 4.11 months (p = 0.19); OS 9.6 vs. 8.3 months (p = 0.75); bevacizumab + lomustine vs. bevacizumab [288]
	NCT00883298	04/2009–03/2017	Combined with TMZ twice a week	II	R
	Results (30 patients): PFS 5.5 months; OS 51 weeks [289]
	NCT00345163	06/2006–05/2017	Combined with or not combined with irinotecan	II	R
	Results (167 patients): PFS-6 42.6% vs. 50.3% (p < 0.0001); PFS 4.2 vs. 5.6 months; OS 9.2 months vs. 8.7 months; bevacizumab alone vs. bevacizumab + irinotecan [276]
	NCT01474239	11/2011–03/2016	Compared with fotemustine	II	R
	Results (91 patients): PFS 3.38 vs. 3.45 months; OS 7.3 vs. 8.7 months; bevacizumab vs. fotemustine (no statistical data) [290]
	NCT02761070	05/2016–02/2019	Combined with high-dose TMZ compared to bevacizumab alone	III	R
	Results: ongoing studies (recruitment)
	NCT02743078	04/2016–11/2019	Combined with Optune^®	II	R Beva refractory or resistant to Beva
	Unpublished data
	NCT01894061	07/2013–03/2020	Combined with NovoTTF	II	R
	Unpublished data
	NCT01814813	03/2013–06/2019	Combined with vaccination (HSPPC-96) compared to bevacizumab alone	II	R
	Preliminary results (90 patients): PFS 3.7 vs. 2.5 vs. 5.3 months (p < 0.01); OS 6.6 vs. 9.2 vs. 10.7 months (p = 0.16); HSPPC-96 + Bevacizumab concomitant vs. HSPPC-96 + bevacizumab on progression vs. bevacizumab alone
	NCT01730950	11/2012–03/2020	Combined with re-irradiation, compared to bevacizumab alone	II	R
	Preliminary results (170 patients): PFS 8.9 vs. 7.9% (p = 0.05; HR = 0.73); OS 25.1 vs. 21.6% (p = 0.46; HR = 0.98); bevacizumab alone vs. bevacizumab + RT
	NCT00967330	08/2009–11/2015	Combined with RT, then in adjuvant therapy combined with Irinotecan compared to the Stupp protocol	II	N. MGMT non methylated
	Results (182 patients): PFS 5.99 vs. 9.7 months (HR = 0.57; p < 0.001); OS 16.6 vs. 17.5 months (HR = 1.02; p = 0.55); TMZ vs. bevacizumab + irinotecan [291]
	NCT02343549	01/2015–07/2019	Combined with Optune^® and TMZ	II	N
	Results: ongoing studies (recruitment)
	NCT01290939	02/2011–02/2018	Combined with lomustine	III	R
	Results (437 patients): PFS 4.2 vs. 1.5 months (HR = 0.49; p < 0.001); OS 9.1 vs. 8.6 months (HR = 0.95; p = 0.65); bevacizumab + lomustine vs. lomustine alone [292]
	NCT00611325	02/2008–03/2014	Combined with bortezomib	II	R
	Results (56 patients): PFS 2 vs. 2.5 months; OS 8 vs. 6 moonths; PFS-6 25 vs. 28.6%; EIAED vs. non-EIAED
	NCT01269853	01/2011–05/2019	Intracerebral administration	I/II	R
	Results: ongoing studies (recruitment)
	NCT01811498	03/2013–05/2019	Intracerebral administration	I/II	N
	Results: ongoing studies (recruitment)
	NCT02511405	07/2015–10/2018	Combined with VB-111 (antiangiogenic), compared to bevacizumab alone	III	R
	Results (256 patients): OS 6.8 vs. 7.9 months (p = 0.19; HR = 1.20) combined vs. bevacizumab alone [293]
	NCT00612339	02/2008–05/2013	Combined with TMZ	II	Non resectable
	Results (41 patients): RR 24.4%
	NCT03149003	05/2017–01/2020	Combined with DSP-7888 (peptide vaccine) compared to bevacizumab alone	II	R
	Results: ongoing studies (no recruitment)
	NCT00501891	07/2007–05/2013	Combined with TMZ	II	R
	Results (32 patients): PFS 15.8 weeks; OS 37.1 weeks [294]
	NCT00597402	01/2008–05/2014	Combined with RT/TMZ, then combined with irinotecan	II	N
	Results (75 patients): PFS 14.2 months; OS 21.2 months [295]
	NCT00433381	02/2007–09/2018	Combined with irinotecan or combined with TMZ	II	R
	Unpublished data
	NCT00613028	02/2008–06/2013	Combined with etoposide or TMZ	II	R Resistant to Beva/Irinotecan
	Results (22 patients): PFS 4.1 vs. 8.1 weeks; OS 12.6 vs. 19 weeks; PFS-6 0 vs. 7.7%; bevacizumab + TMZ vs. bevacizumab + etoposide
	NCT00612430	02/2008–08/2013	Combined with etoposide	II	R
	Results (27 GBM et 32 grade III glioma patients): PFS6 40.6% & 44,4%; OS 63.1 & 44.4 weeks [296]
	NCT00884741	04/2009–07/2019	Combined with adjuvant TMZ compared to the Stupp protocol	III	N
	Results (621 patients): PFS 10.7 months vs. 7.3 months (HR 0.79; p 0.007); OS 15.7 months vs. 16.1 months (HR 1.13; p 0.21) (bevacizumab + Stupp vs. Stupp + placebo) [297]
	NCT00463073	04/2007–12/2008	Combined with cetuximab and irinotecan	II	R
	See Cetuximab
	NCT01884740	06/2013–01/2017	Combined with cetuximab and intracranial administration	I/II	N aged under 22
	See Cetuximab
	NCT00525525	09/2007–05/2014	Combined with erlotinib, TMZ in adjuvant therapy	II	N
	See Erlotinib
	NCT00720356	06/2008–10/2018	Combined with erlotinib, in adjuvant therapy after RT/TMZ	II	N
	See Erlotinib
	NCT00671970	01/2008–03/2013	Combined with erlotinib	II	R
	See Erlotinib
	NCT00892177	05/2009–10/2019	Combined with dasatinib and compared with bevacizumab alone	II	R
	See Dasatinib
	NCT00667394	04/2008–10/2015	Combined with tandutinib	II	R
	See Tandutinib
	NCT00923117	07/2009–09/2015	Sunitinib in monotherapy with or without bevacizumab	II	R
	See Sunitinib
	NCT00800917	12/2008–01/2010	Combined with temsirolimus	II	R
	See Temsirolimus
NCT00805961	12/2008–08/2013	Combined with everolimus in adjuvant therapy after RT/TMZ	II	N
See Everolimus
NCT03463265	08/2018–12/2020	Monotherapy (ABI-009) or in combination with bevacuzimab or RT/TMZ or marizomib, or lomustine	II	R/N
See ABI-009
NCT01349660	04/2011–01/2017	Combined with buparlisib	I/II	R
See Buparlisib
NCT00586508	12/2007–10/2013	Combined with enzastaurin	II	N
See Enzastaurin
NCT00621686	02/2008–01/2017	Combined with sorafenib	II	R
See Sorafenib
NCT01632228	06/2012–02/2018	Onartuzumab combined or not with bevacizumab, compared to bevacizumab alone	II	R
See Onartuzumab
NCT01113398	04/2010–12/2015	Rilotumumab combined with bevacizumab	II	R
See Rilotumumab
NCT01648348	06/2012–05/2018	TRC105 combined with bevacizumab, compared to bevacizumab alone	II	R
See TRC105
NCT01564914	03/2012–06/2019	TRC105 combined with bevacizumab	II	R treated with Bevacizumab
See TRC105
NCT01290263	02/2011–07/2017	Trebananib combined or not with bevacizumab	I/II	R
See Trebananib
VEGFR	Pazopanib
	NCT02331498	11/2014–07/2019	Combined with the Stupp protocol	I/II	N
	Results: ongoing studies (recruitment)
	NCT00459381	04/2007–03/2017	Monotherapy	II	R
	Results (35 patients): PFS 12 weeks; OS 35 weeks; PFS-6 3% [298]
	NCT01931098	08/2013–03/2020	Combined with topotecan	II	R
	Results (35 patients): OS 42 weeks; PFS 24 weeks; PFS-6 46%; OS-6 77% [277]
	NCT00350727	07/2006–04/2013	Combined with lapatinib	II	R
	See Lapatinib
	Cediranib
	NCT01310855	03/2011–05/2017	Combined with Gefitinib, compared to cediranib and placebo	II	R
	Results (97 patients): PFS 3.6 vs. 2.8 months (p = 0.17; HR = 0.72); OS 7.2 months vs. 5.5 months (HR = 0.68); cediranib + gefetinib vs. cediranib + placebo [299]
	NCT00777153	10/2008–12/2016	Monotherapy or combination with lomustine, compared with lomustine alone	III	R
	Results (325 patients): PFS 92 vs. 125 vs. 44 days (p = 0.90; 0.16; HR = 1.05; 0.76); OS 8 vs. 9.4 vs. 9.8 months (p = 0.10; 0.50; HR = 1.43; 1.15); cediranib vs. cediranib + lomustine vs. lomustine + placebo [300]
	NCT02974621	11/2016–03/2020	Combined with olaparib and compared to bevacizumab	II	R
	Results: ongoing studies (no recruitment)
	NCT01062425	02/2010–03/2020	Combined with TMZ in the Stupp protocol, compared to the Stupp protocol	II	N
	Preliminary data (149 patients): PFS 2.7 vs. 6.2 months (p = 0.03; HR = 0.67); OS 13.8 vs. 14.5 months (p = 0.44; HR = 0.87); Stupp vs. cediranib + Stupp
	NCT00662506	04/2008–09/2017	Combined with TMZ/RT	II	N
	Unpublished data
	NCT00305656	03/2006–08/2013	Monotherapy	II	R
	Results (31 patients): PFS 117 days; OS 227 days [301]
	Nintedanib
	NCT01251484	12/2010–10/2012	Monotherapy (after treatment with the Stupp protocol or with bevacizumab)	II	R
	Results (25 patients): PFS 1 vs. 1 month; OS 10 vs. 2 months (p < 0.02); previous treatment with Stupp vs. bevacizumab [302]
	NCT01666600	06/2012–11/2017	Combined with RT, compared to RT alone	I/II	R
	Unpublished data
	NCT01380782	06/2011–08/2014	Monotherapy	II	R whether or not treated with Bevacizumab
	Results (36 patients): PFS 28 vs. 28 days; OS 6.9 vs. 2.6 months; not treated with bevacizumab vs. 1st line with bevacizumab (No statistical data) [303]
	Dovitinib
	NCT01753713	12/2012–12/2017	Monotherapy	II	R whether or not treated with Bevacizumab
	Results (33 patients): PFS 2 vs. 1.8 months; OS 8 vs. 4.3 months; bevacizumab-naive vs. 1st line with bevacizumab
	Vandetanib (see Multikinase inhibitors)
	NCT00441142	02/2007–04/2017	Combined with the TMZ of the Stupp protocol	I/II	N
	See Multikinase inhibitors
	NCT00995007	10/2009–02/2016	Combined with carpoblatin and compared to carboplatin alone	II	R
	See Multikinase inhibitors
	Vatalanib
	NCT00128700	08/2005–09/2012	Combined with TMZ/RT	I/II	N
	Results (20 patients): PFS 7.2 months; OS 16.2 months [304]
	Tivozanib
	NCT01846871	03/2013–01/2019	Monotherapy	II	R
	Results (10 patients): PFS-6 10%; PFS 2.3 months; OS 8.1 months [305]
	Axitinib
	NCT01562197	03/2012–01/2019	Monotherapy or combined with lomustine	II	R
	Unpublished data
	NCT01508117	01/2012–09/2017	Combined with RT	II	N elderly
	Results (1 patient): OS 0.2 years
	NCT03660761	09/2018–04/2019	Combined with TMZ	II	R
	Unpublished data
	CT-322
	NCT00562419	11/2007–10/2010	Combined with irinotecan	II	R
	Results: ongoing studies (recruitment unknown)
	Semaxanib (SU5416)
	NCT00004868	03/2003–06/2018	Monotherapy	I/II	R RT non-responder
	Unpublished data
	Tanibirumab
	NCT03856099	02/2019–03/2020	Monotherapy	II	R
	Results: ongoing studies (recruitment)
	NCT03033524	01/2017–01/2017	Monotherapy	II	R
	Results: ongoing studies (recruitment unknown)

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 green, 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.