Shattering the castle walls: Anti-stromal therapy for pancreatic cancer

Table 1 Summary of existing studies evaluating the efficacy of anti-stromal agents in the treatment of metastatic pancreatic cancer

Agent	Target	Treatment arm (s)	Type of study	National clinical trial number	Status	Results
Paricalcitol	Vitamin D metabolic pathway	Gemcitabine and nab-paclitaxel plus paricalcitol or placebo	Phase I/II	NCT03520790	Recruiting
		Nab-paclitaxel, cisplatin and gemcitabine plus paricalcitol	Phase II	NCT03415854	Recruiting
		Nivolimumab1, nab-paclitaxel, cisplatin, and gemcitabine plus paricalcitol	Phase II	NCT02754726	Recruiting
		Pembrolizumab1 plus paricalcitol or placebo	Phase II	NCT03331562	Recruiting
All trans retinoic acid	Pancreatic stellate cells	Gemcitabine and nab-paclitaxel plus all trans retinoic acid	Phase I	NCT03307148	Recruiting
Vismodegib	Hedgehog signaling	Gemcitabine plus vismodegib or placebo	Phase I/II	NCT0106422	Completed	Vismodegib did not improve ORR, PFS and OS
IPI-926	Hedgehog signaling	FOLFIRINOX plus IPI-926	Phase I	NCT01383538	Completed	The combination treatment was safe but IP-926 was not beneficial
		Gemcitabine plus IPI-926 or placebo	Phase I/II	NCT01130142	Completed	The combination treatment was well tolerated, and showed promising activity
PEGPH20	Hyaluronic acid	Gemcitabine and nab-paclitaxel plus PEGPH20 vs chemotherapy alone	Phase II	NCT01839487	Completed	PEGPH20 significantly improved PFS, especially in patients having tumors with high-level hyaluronic acid
		Gemcitabine and nab-paclitaxel plus PEGPH20 or placebo2	Phase III	NCT02715804	Recruiting
		Modified FOLFIRINOX plus PEGPH20 vs chemotherapy alone	Phase I/II	NCT01959139	Closed	PEGPH20 was found to have a detrimental effect on OS

¹Nivolimumab and Pembrolizumab: PD-1-targeted T-cell checkpoint inhibitors;

²This study included only patients whose tumors had high levels of hyaluronic acid. ORR: Overall response rate; PFS: Progression-free survival; OS: Overall survival; FOLFIRINOX: 5-fluorouracil, irinotecan and, oxaliplatin.