Table 3.
The list of clinical trials of VEGF/VEGFR targeting therapeutic targets/agents in GBM patients
| Agent/inhibitor | Angiogenic targets | Phase | Tumor type | Combination | Reference |
|---|---|---|---|---|---|
| Aflibercept | VEGF-A/B, PIGF | I | rGBM, newly diagnosed GBM, MG | With TMZ and XRT | http://www.clinicaltrials.gov |
| Bevacizumab | VEGF-A | I/II/III | rGBM | With various combinations | [135, 136, 180] |
| AEE788 | VEGFR1-R2 | I/II | rGBM | http://www.clinicaltrials.gov | |
| EGFR | I/II | rGBM | With Everolimus | http://www.clinicaltrials.gov | |
| Cediranib | VEGFR1 to R3 | I/II | Newly diagnosed GBM | With TMZ and XRT | [163] |
| PDGFR-β, c-Kit | III | rGBM | Versus Lomustine (randomized trial) | http://www.clinicaltrials.gov | |
| Pazopanib (GW786034) | VEGFR1-R3 | II | rGBM | http://www.clinicaltrials.gov | |
| PDGFR-β, c-Kit | II | rGBM | With Lapanitib | http://www.clinicaltrials.gov | |
| I | rGBM | With Lapanitib | http://www.clinicaltrials.gov | ||
| Sorafenib | VEGFR2-R3 | I/II | rGBM, newly diagnosed GBM | With Erlotinib | http://www.clinicaltrials.gov |
| BRAF, PDGFR-β, c-Kit, Ras, p38α | I/II | rGBM, newly diagnosed GBM | With Erlotinib, Tipifarnib, or Temsirolimus | http://www.clinicaltrials.gov | |
| I/II | rGBM | With Temsirolimus | http://www.clinicaltrials.gov | ||
| Sunitinib | VEGFR2, PDGFR-β | I | rGBM, rMG | With Irinotecan | http://www.clinicaltrials.gov |
| Flt-3, c-Kit | II | rMG | http://www.clinicaltrials.gov | ||
| Vandetanib (ZD6474, Zactima®) | VEGFR2, EGFR | I/II | Newly diagnosed GBM | With TMZ and XRT | http://www.clinicaltrials.gov |
| RET | I | rMG | With Imatinib and Hydroxyurea | http://www.clinicaltrials.gov | |
| Vatalanib (PTK787) | VEGFR1-R3 | I | Newly diagnosed GBM | With TMZ and XRT | [181] |
| PDGFR-β and c-Kit | I/II | Newly diagnosed GBM | With TMZ and XRT with or without Vatalanib (randomized trial) | http://www.clinicaltrials.gov | |
| Dastinib | PDGFR-β, Src, BCR-ABL, | I | rMG | With Erlotinib | http://www.clinicaltrials.gov |
| c-Kit, EphA2 | II | rGBM | http://www.clinicaltrials.gov | ||
| Imatinib | PDGFR-β, BCR-ABL, c-Kit | I | rMG | With Everolimus and Hydroxyurea | http://www.clinicaltrials.gov |
| Tandutinib (MLN518) | PDGFR-β, c-Kit, Flt-3 | I/II | rGBM | http://www.clinicaltrials.gov | |
| II | rMG | With Bevacizumab | http://www.clinicaltrials.gov | ||
| Panzem® (2ME2) | HIF-1A | II | rGBM | With TMZ schedule | http://www.clinicaltrials.gov |
| II | rGBM | http://www.clinicaltrials.gov | |||
| Metronomic TMZ | Endothelial progenitor cells, endothelial cells | II | Newly diagnosed GBM |
With gliadel wafer, TMZ, and XRT With Retinoic acid (TMZ with Retinoic acid) |
http://www.clinicaltrials.gov |
| Celecoxib | COX-2 | II | GBM with XRT | With Celecoxib, Thalidomide, and Isotretinoin | http://www.clinicaltrials.gov |
| II | rMG | Capecitabine, 6-thioguanine with TMZ or Lomustine | http://www.clinicaltrials.gov | ||
| Cilengitide | Integrins ανβ3 and ανβ5 | I/II | Newly diagnosed GBM | With TMZ and XRT | http://www.clinicaltrials.gov |
| III | Newly diagnosed GBM | With TMZ and XRT | http://www.clinicaltrials.gov | ||
| I/II | rMG | With monotherapy (several clinical trials) | http://www.clinicaltrials.gov |
COX-2 cyclo-oxygenase-2, EGFR epithelial growth factor receptor, EIAEDs enzyme-inducing anti-epileptic drug, VEGF vascular endothelial growth factor, VEGFR vascular endothelial growth factor receptor, PDGFR platelet endothelial growth factor receptor, HIF1A hypoxia-inducible growth factor 1 alpha, PIGF placental growth factor, rGBM recurrent GBM, rMG recurrent malignant glioma, XRT radiation therapy