Table 2.

Representative clinical trials of anti-angiogenic drug targets in GBM

Clinical trial no.	Antiangiogenic drug targets	Clinical trial phase	Clinical trial institution	Brain tumor disease type	Number of patients enrolled (n)	Concentration	PFS-6 (%)	Median OS (months)	Reference
1	Bevacizumab (BEV)	II	BRAIN	Recurrent GBM	85	10 mg/kg every 2 weeks	43	9.3	[137]
	Bevacizumab + Irinotecan	II	BRAIN	Recurrent GBM	167	10 mg/kg of BEV + Irinotecan (340 mg/m2 or 125 mg/m2) every 2 weeks	50.3	8.7	[137]
2	Bevacizumab (BEV)	II	NCI	Recurrent GBM	48	10 mg/kg every 2 weeks	29	7.8	[134]
3	Bevacizumab (BEV) + Lomustine	II	BELOB	Recurrent GBM	153	10 mg/kg every 2 weeks + 110 mg/m2 once every 6 weeks	42	12	[138]
4	Bevacizumab (BEV) + Lomustine	III	EORTC 26101	Recurrent GBM	437	10 mg/kg every 2 weeks +110 mg/m2 once every 6 weeks	Not recorded	9.1	[139]
5	Cediranib	III	REGAL	Recurrent GBM	118	30 mg daily given one time	16	8	[168]
		III	REGAL	Recurrent GBM	325	30 mg daily + 110 mg/m2 once every 6 weeks	35	9.4	[168]
		III	REGAL	Recurrent GBM	325	30 mg daily + Cediranib matched placebo	25	9.8	[168]
6	Enzastaurin	III	Phase-III Enzastaurin Study	Recurrent GBM	266	500 mg daily	11.1	6.6	[169]
			Phase-III Enzastaurin Study	Recurrent GBM	266	500 mg daily + 110 to 130 mg/m2 once every 6 weeks	19	7.1	[169]
7	Aflibercept	II	Phase-II Aflibercept Study	Recurrent GBM	42	4 mg/kg every 2 weeks	7.7	9.8	[170]
8	Nintedanib	II	Phase-II Nintedanib Study	Recurrent GBM	13	200 mg twice daily	4	8.1	[171]
9	Pazopanib	II	Phase-II Pazopanib Study	Recurrent GBM	35	800 mg daily	3	8.8	[172]
10	Pazopanib	I/II	Phase I/II Pazopanib plus Lapatinib Study	Recurrent GBM	41	400 mg daily plus 1000 mg/day Lapatinib	7.5	Not recorded	[173]
11	Sorafenib	II	Phase II study of Sorafenib Study	Recurrent GBM	32	400 mg daily	9.4	10.4	[174]
		II	Phase II study of Sorafenib Study	Recurrent GBM	32	400 mg daily plus TMZ daily	9.4	10.4	[174]
12	Sunitinib	II	Phase II study of Sorafenib Study	Recurrent GBM	32	37.5 mg daily	10.4	9.4	[175]
13	Vandetanib	I/II	Phase I/II Clinical Trial of Vandetanib	Recurrent GBM	32	300 mg daily	6.5	6.3	[176]
14	Bevacizumab (BEV) + TMZ/XRT	III	RTOG 0825 Brain Committee	Newly diagnosed GBM	637	10 mg/kg every 2 weeks + TMZ	Not recorded	15.7	[177]
15	Bevacizumab (BEV) + TMZ/XRT	III	AVAGlio	Newly diagnosed GBM	921	10 mg/kg every 2 weeks + TMZ/XRT	Not recorded	16.9	[140]
16	Bevacizumab (BEV) + TMZ/XRT	III	AVAGlio	Newly diagnosed GBM	463	10 mg/kg every 2 weeks + TMZ/XRT	Not recorded	16.8	[140]
17	Bevacizumab (BEV) + Irinotecan/XRT	II	GLARIUS	Newly diagnosed GBM (MGMT unmethylated)	116	10 mg/kg every 2 weeks + IRI 125 mg/m2 every 2 weeks	71.1	16.6	[141]
		II	GLARIUS	Newly diagnosed GBM	54	75 mg/m2 TMZ daily/XRT	26.2	17.3	[141]
18	Cilengitide (CIL)	II	The CORE Study	Newly diagnosed GBM/negative MGMT	265	2000 mg twice per weeks + TMZ/XRT	5.6	16.3	[178]
	TMZ/XRT					2000 mg five times per weeks + TMZ/XRT	5.9	14.5
19	Cilengitide (CIL) + TMZ/XRT	III	The CENTRIC Study	Newly diagnosed GBM/positive MGMT	545	2000 mg twice per weeks + TMZ/XRT	13.5	26.3	[179]
20	Cilengitide (CIL) + TMZ plus Procarbazine/XRT	II	The ExCentric Study	Newly diagnosed GBM/negative MGMT	48	2000 mg twice per weeks + TMZ plus Procarbazine/XRT	30 weeks	58 weeks	[139]

IRI irinotecan, MGMT O6-methylguanine-DNA methyltransferase, OS overall survival, PFS progression-free survival, TMZ temozolomide, XRT radiation therapy]