Treatment strategies for oesophagogastric junction adenocarcinoma have not been standardized despite its poor prognosis due to differences in the incidence rates between Western countries and Asia. This randomized Phase II/III trial was initiated in June 2023 to determine which neoadjuvant chemotherapy regimen, docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel, is a more promising treatment in Phase II and confirm the superiority of neoadjuvant chemotherapy with docetaxel, oxaliplatin and S-1 or fluorouracil, oxaliplatin and docetaxel followed by surgery and postoperative chemotherapy over upfront surgery and postoperative chemotherapy in terms of overall survival in patients with Clinical Stage III or IVA oesophagogastric junction adenocarcinoma in Phase III. A total of 460 patients, including 150 patients in Phase II and 310 patients in Phase III, are planned to be enrolled from 85 hospitals in Japan over 5 years. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230182 (https://jrct.niph.go.jp/latest-detail/jRCTs031230182).

Although the efficacy of postoperative therapy with nivolumab after preoperative chemoradiotherapy for locally advanced oesophageal cancer has been proven in Western countries, the survival benefits of postoperative therapy after preoperative chemotherapy with docetaxel, cisplatin and 5-FU or cisplatin plus 5-FU as the Japanese standard therapy remain controversial. This randomized Phase III trial was designed to confirm the superiority of postoperative therapy with nivolumab over observation alone and S-1 over observation alone in patients with locally advanced oesophageal squamous cell carcinoma with no pathological complete response after preoperative chemotherapy followed by curative esophagectomy. A total of 450 patients will be enrolled from 56 hospitals in Japan over 5.5 years. The primary endpoint is relapse-free survival, and the secondary endpoints are disease-free survival, overall survival, adverse events and incremental cost-effectiveness ratio. This trial has been registered in the Japan Registry of Clinical Trials as jRCTs031230219 (https://jrct.niph.go.jp/latest-detail/jRCTs031230219).

The standard approach for stage IV gastric cancer is palliative chemotherapy. However, despite the advancements in various chemotherapy regimens, the prognosis remains poor, highlighting the urgent need to develop more effective treatment strategies. The controversy persists regarding the integration of a local therapy including surgery in the management of unresectable stage IV gastric cancer. This randomized phase III trial aims to confirm the additional benefit of conversion surgery following palliative chemotherapy compared with palliative chemotherapy alone with respect to overall survival in patients initially diagnosed with unresectable clinical stage IVB or pathological stage IV gastric cancer after a remarkable response to chemotherapy. This study plans to enroll 126 patients from 63 institutions in Japan for 5 years, and it has been registered in the Japan Registry of Clinical Trials as jRCTs031240340 (https://jrct.niph.go.jp/latest-detail/jRCTs031240340).

The need for prophylactic supraclavicular lymph node dissection during esophagectomy with radical lymphadenectomy remains controversial. A randomized phase III trial was launched in August 2022 to confirm the non-inferiority of esophagectomy with D2 lymphadenectomy except for supraclavicular lymph node dissection to standard D2 lymphadenectomy in terms of overall survival for patients with resectable upper or middle thoracic esophageal cancer. This study will enroll 480 patients from 54 Japanese institutions over 5 years. The primary endpoint includes overall survival, and the secondary endpoints include relapse-free survival, perioperative and late complication incidences, supraclavicular lymph node recurrence, salvage cervical treatment incidence, synchronous cervical and abdominal procedure proportion, operation time and the number of operating surgeons. This trial has been registered at the Japan Registry of Clinical Trials under study number jRCT1030220248.

Patients with peripheral T-cell lymphoma demonstrated a poor prognosis after obtaining a complete response with induction treatment compared to those with B-cell lymphoma. Once it relapsed, curative treatment is frequently limited to invasive treatments with significant treatment-related mortality, including allogeneic stem cell transplantation. The limitations of these treatment choices indicate the necessity for developing optimal consolidation therapies to prevent relapse. This multicenter randomized phase III trial aims to confirm the superiority of the high-dose therapy with autologous stem cell transplantation over observation alone in terms of progression-free survival for patients with newly diagnosed peripheral T-cell lymphoma who achieved complete metabolic response after induction therapy. A total of 140 patients from 52 hospitals will be enrolled in Japan over 5.5 years. This trial is registered in the Japan Registry of Clinical Trials as jRCTs031240169 (https://jrct.niph.go.jp/latest-detail/jRCTs031240169).