Table 1. Recent clinical trials employing antiangiogenic therapy for newly diagnosed and recurrent GBM.

	Clinical trial identifier	Eligibility criteria	Study end point(s)	Treatment groups
Primary
Bevacizumab	NCT00943826 (AVAglio) [41]	Newly diagnosed, histologically confirmed GBM Stable or decreasing steroid dose within 5 days prior to randomization	Primary: PFS and OS Secondary: 1- and 2-year survival rate, quality of life, adverse events	Arm I: Bevacizumab 10 mg/kg + RT + TMZ 75 mg/m2 Arm II: RT + TMZ 75 mg/m2
	NCT00884741 (RTOG 0825) [40]	Newly diagnosed, histologically confirmed GBM with supratentorial component (partial or complete resection) No recurrent or multifocal malignant glioma No prior TMZ or bevacizumab	Primary: PFS and OS (from randomization) Secondary: Treatment-related toxicity, molecular profile	Arm I: RT + TMZ Arm II: RT + TMZ + bevacizumab
	NCT00967330 (GLARIUS) [42]	Histologically confirmed GBM No previous chemotherapy or RT for GBM Non-methylated MGMT promoter	Primary: 6-month PFS Secondary: OS, response rate, time to treatment failure, adverse events, quality of life	Arm I: Bevacizumab 10 mg/kg every 2 wks + irinotecan 125 mg/m2 every 2 wks + TMZ 75 mg/m2 Arm II: TMZ 75 mg/m2
Cediranib	NCT00662506 [26]	Histologically confirmed newly diagnosed GBM Scheduled to receive standard post-surgical RT + TMZ	Primary: Safety profile and optimal dosing of cediranib during TMZ (Phase I) PFS (Phase II) Secondary: MRI parameters, blood biomarkers, tumor biomarkers	Arm I: Cediranib + TMZ (dose-limiting toxicity 15 mg, 20 mg, 30 mg)
	NCT01062425	Histologically confirmed newly diagnosed GBM with supratentorial component No recurrent or multifocal malignant glioma	Primary: 6-month PFS Secondary: PFS and OS (from randomization), treatment-related toxicity	Arm I: Cediranib + RT + TMZ Arm II: RT + TMZ
Cilengitide	NCT00689221 (CENTRIC) [48]	Newly diagnosed, histologically confirmed supratentorial GBM Methylated MGMT promoter	Primary: OS (from time of randomization) Secondary: PFS, pharmacokinetics, quality-of-life assessment and safety and tolerability	Arm I: Cilengitide + RT + TMZ ARM II: RT + TMZ
	2004-004849-18 (EMD121974-010) [47]	Newly diagnosed, histologically confirmed supratentorial GBM Stable or decreasing dose of steroids for ≥ 8 days	Primary: 6-month PFS Secondary: Response rate, OS, 1-year survival rate, median time to progression, pharmacokinetics of cilengitide + TMZ, safety and tolerability	Arm I: Cilengitide + RT + TMZ Arm II: RT + TMZ
	NCT00813943 (CORE) [49]	Newly diagnosed, histologically confirmed supratentorial GBM Non-methylated MGMT promoter	Primary: OS (from time of randomization) Secondary: PFS (from randomization), pharmacokinetics, adverse events	Arm I: Cilengitide (twice weekly) + TMZ + RT Arm II: Cilengitide (five times weekly) + TMZ + RT Arm III: TMZ + RT
Recurrent
Bevacizumab	NTR1929 (BELOB) [33]	Histologically confirmed GBM First relapse after prior treatment with standard RT/TMZ No prior treatment with nitrosoureas or VEGF-R signaling inhibitors	Primary: 9-month OS Secondary: Response rate, median PFS and OS, 6- and 12-month PFS, quality of life	Arm I: Bevacizumab 10 mg/kg every 2 wks Arm II: Bevacizumab 10 mg/kg every 2 weeks + 110 mg/m2 lomustine every 6 wks Arm III: Lomustine 110 mg/m2 every 6 wks
	ACTRN12610000915055 (CABARET) [34]	Histologically confirmed GBM Prior treatment with standard RT/TMZ Recurrent/progressive disease confirmed by surgical resection or MRI	Primary: PFS Secondary: OS, Response rate, MMSE cognitive function, quality of life, corticosteroid dose, toxicity, time to treatment failure	Arm I: Bevacizumab every 2 wks until disease progression Arm II: Bevacizumab every 2 wks + carboplatin every 4 wks until disease progression
Cediranib	NCT00305656 [36]	Histologically confirmed GBM Contrast-enhancing tumor ≥ 1 cm in longest diameter	Primary: Rate of 6-month PFS Secondary: Response rate, OS, toxicity profile	Arm I: Cediranib once daily on days 1 – 28
	NCT00777153 (REGAL) [37]	Histologically confirmed recurrent GBM Receive one prior chemotherapy with TMZ	Primary: PFS Secondary: OS (from randomization), response rate, progression-free rate at 6 months, steroid-free days	Arm I: Cediranib 30 mg Arm II: Cediranib 20 mg + lomustine Arm III: Lomustine alone
	NCT01310855 (DORIC)	Histologically or cytologically confirmed GBM No other prior treatment for GBM except Gliadel or steroids Recurrent or progressive disease after standard therapy	Primary: PFS (from randomization) Secondary: OS (from randomization), response rate, progression-free rate at 6 months, steroid use	Arm I: Cediranib 30 mg + gefitinib 500 mg Arm II: Cediranib alone
Cilengitide	NCT00093964 (EMD 121974-009) [93]	Recurrent or progressive GBM following surgery or biopsy RT and one previous regimen of systemic chemotherapy Solid contrast-enhancing lesion ∼ 1 cm in any dimension within 2 weeks prior to the first dose of cilengitide	Primary: Rate of 6-month PFS Secondary: Response rate, time to disease progression, survival time, safety, tolerability and pharmacokinetics	Arm I: Cilengitide 500 mg twice weekly Arm II: Cilengitide 2,000 mg twice weekly

GBM: Glioblastoma; kg: Kilograms; m²: Meters squared; mg: Milligrams; MGMT: O(6)-methylguanine-DNA methyltransferase; OS: Overall survival; PFS: Progression-free survival; RT: Radiation therapy; RTOG: Radiation therapy oncology group; TMZ: Temozolomide; wks = Weeks.