Table 1.

Summary of clinical trials modulating the tumor microenvironment and metabolic reprogramming in PCa patients.

Drug	Targeted Pathway	Phase/Patient Number	Intervention	Subject Population	Results	Refs
PEGPH20	HA	Phase 1b/II n = 138	mFOLFIRINOX	Metastatic PCa	Grade 3 to 4 toxicity and worsened OS	NCT01959139 [127]
PEGPH20	HA	Phase III n = 494	Gem + nab-PTX	Metastatic PCa	Grade 3 to 4 toxicity and worsened OS	NCT02715804 [128]
Vismodegib	Hedgehog pathway	Phase Ib/II n = 106	Gem	Metastatic PCa	Does not improve overall response rate, PFS, or OS	NCT01064622 [129]
Vismodegib	Hedgehog pathway	Phase II n = 71	Gem + nab-PTX	Metastatic PCa	Does not improve overall response rate, PFS, or OS	NCT01088815 [130]
Bevacizumab	VEGF pathway	Phase III n = 535	Gem	Advanced PCa	Does not improve OS	NCT00088894 [131]
Bevacizumab	VEGF pathway	Phase III n = 607	Gem + erlotinib	Metastatic PCa	Does not improve OS, improved PFS	NCT01214720 [132]
Axitinib	VEGF pathway	Phase III n = 632	Gem	Advanced PCa	Does not improve OS, improved PFS	NCT00471146 [133]
Sorefenib	VEGF, PDGF and RAF pathway	Phase III n = 102	Gem	Advanced PCa	Does not improve overall response rate, PFS, or OS	NCT00541021 [134]
HCQ	Autophagy	Phase II/n = 98	Gem + nab-PTX	Preoperative PCa	Greater tumor response, improved serum biomarker response, and immune activity	NCT01978184 [135]
HCQ	Autophagy	Phase II/n = 112	Gem + nab-PTX	Metastatic PCa	Greater pathological tumor response, but not OS	NCT01506973 [136]

Gem: Gemcitabine; nab-PTX: Nab-paclitaxel; HCQ: Hydroxychloroquine; OS: Overall survival; PFS: Progression-free survival.