Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives

Table 5 Ongoing clinical trials

Study name/phase	Size/stage/primary tumor location/histology	Intervention	Primary endpoint
NCT02730546/Phase Ib/II suspended	68 patients/IB-IIIB/GEJ cardia/adenocarcinoma	E: carboplatin, paclitaxel + radiation or 5-FU, oxaliplatin, leucovorin + pembrolizumab → surgery	pCR and 1-yr PFS rate
PROCEED/phase II/NCT03064490recruiting	38 patients/locally advanced stomach GEJ esophagus/adenocarcinoma	E: carboplatin, paclitaxel + 45 Gy radiation + pembrolizumab → surgery → pembrolizumab	pCR
NCT03257163/phase II recruiting	40 patients/IB-IIIC/gastric adenocarcinoma MSI or EBV positive	E: pembrolizumab → surgery → pembrolizumab + capecitabine + radiation	3-yr RFS rate
NCT03776487/phase I/II recruiting	30 patients/0-IVA/stomach GEJ/adenocarcinoma	E: oxaliplatin, 5-FU + nivolumab, ipilimumab + radiation → surgery → nivolumab	Tolerability
NCT00857246/phase II/completed	30 patients/T3N0, T4, TanyN1-3, M0/stomach GEJ	E: induction cisplatin, irinotecan + cetuximab → surgery → cetuximab + 5-FU/LV + 37.5 Gy radiation	RR
NCT01183559/phase I/completed	9 patients/potentially resectable/esophagus GEJ stomach	E: vandetanib + carboplatin, paclitaxel + 5-FU + 45 Gy radiation → surgery	Maximum tolerated dose: 200 mg vandetanib
NCT04162665/recruiting	36 patients/T1-T2N1, T3Nany/stomach AEG3/adenocarcinoma	E: MRI guided 25 Gy radiation + oxaliplatin, capecitabine	pCR
NCT04308837/phase II recruiting	29 patients/uT3-4NanyM0/stomach	E: laparoscopic hyperthermic intraperitoneal chemotherapy → carboplatin, paclitaxel + IM radiation T>6M → gastrectomy D2 → oxaliplatin, 5-FU/LV	pCR
CRITICS-II/phase II/NCT02931890/recruiting[83]	207 patients/IB-IIIC/resectable/stomach GEJ/adenocarcinoma	E1: docetaxel, oxaliplatin, capecitabine OR E2: induction docetaxel, oxaliplatin, capecitabine → carboplatin, paclitaxel + 45 Gy radiation OR E3: carboplatin, paclitaxel + 45 Gy radiation AND gastrectomy (all arms)	1-yr EFS rate
Neo-CRAG/phase III	620 patients/cT3N2/N3M0, cT4aN + M0, cT4bNanyM0/gastric adenocarcinoma	E: oxaliplatin, capecitabine + 45 Gy radiation OR C: oxaliplatin, capecitabine AND gastrectomy D2 → oxaliplatin, capecitabine (both arms)	3-yr DFS rate
PREACT/phase III	682 patients/IIB (T3N1 only)-IIIC (excluding T2N3)/stomach GEJ (excluding AEG1)/adenocarcinoma	E: S-1, oxaliplatin + 45 Gy radiation OR C: S-1, oxaliplatin AND gastrectomy D2 → S-1, oxaliplatin (both arms)	3-yr DFS rate
ITACA S-2/phase III/NCT01989858/ terminated	1180 patients/T3-4N0M0, TanyN + M0/stomach/adenocarcinoma	E1: epirubicin, oxaliplatin, capecitabine (EOX) or epirubicin, cisplatin, 5-FU (ECF) → gastrectomy → EOX or ECF OR C1: gastrectomy → EOX or ECF E2: EOX or ECF → gastrectomy → EOX or ECF → capecitabine or 5-FU + 45 Gy radiation OR C2: gastrectomy → EOX or ECF → capecitabine or 5-FU + 45 Gy	5-yr OS rate
Enriched-CRT 2017/phase III/NCT03680261/not yet recruiting	556 patients/pT2-4aN1-3M0 LVI+/stomach GEJ/adenocarcinoma	Gastrectomy D1/D2 (both arms) AND E: oxaliplatin, capecitabine or S-1 + 45 Gy radiation OR C: oxaliplatin, capecitabine or S-1	3-yr OS rate
TOPGEAR/phase III[61]	620 patients/IB (T1N1 only)-IIIC/resectable stomach GEJ/adenocarcinoma	E: induction EOX or ECF or epirubicin, cisplatin, capecitabine (ECX) or docetaxel, oxaliplatin, 5-FU/LV (FLOT) → 5-FU or capecitabine + 45 Gy radiation OR C: induction EOX or ECF or ECX or FLOT AND gastrectomy D1+ → EOX or ECF or ECX or FLOT (all arms)	5-yr OS rate

mOS: Median overall survival; mDFS: Median disease-free survival; mPFS: Median progression-free survival; E: Experimental; C: Control; HR: Hazard ratio; 5-FU: 5-fluorouracil; LV: Leucovorin; Gy: Gray; S-1: Tegafur/gimeracil/oteracil; pCR: Pathologic complete response; GEJ: Gastroesophageal junction; CRT: Chemoradiation; AEG: Adenocarcinomas of the esophagogastric junction; EOX: Epirubicin, oxaliplatin, capecitabine; ECF: Epirubicin, cisplatin, 5-fluorouracil; ECX: Epirubicin, cisplatin, capecitabine; FLOT: Docetaxel, oxaliplatin, 5-fluorouracil/leucovorin.