1920 - TRIANgLE study (JCOG1510): A phase III study of tri-modality combination therapy with induction docetaxel (DOC), cisplatin (CDDP), 5-fluorouracil (FU) (DCF) vs definitive chemoradiotherapy (dCRT) for locally advanced unresectable squamous cell carcinoma (SCC) of the thoracic esophagus

Background

Although standard treatment for locally advanced unresectable esophageal SCC (LAUEC) has been dCRT consisted of CDDP plus FU, treatment outcome is limited. In the phase II trial of induction chemotherapy (Cx) with DCF followed by conversion surgery (CS) or dCRT plus CS for patients (pts) with LAUEC, 39.6% of pts received R0 resection via CS and achieved better 3-year overall survival (OS) of 71.4% with manageable toxicity.

Trial design

Eligibility criteria include as follows; histologically proven SCC, cT4b or cT3 but highly suspicious of cT4b and/or unresectable lymph nodes metastasis (LNM) invading to adjacent organs, no distant metastasis except for supraclavicular LNM, age 20 to 75, and performance status 0-1. Pts are randomized into following two arms stratified by institution, invasion to adjacent organs (definitive versus suspicious) and supraclavicular LNM (yes versus no). Pts in arm A receive dCRT consisted of CDDP (70 mg/m²/day, days 1 and 29) and FU (700 mg/m²/day, days 1-4 and 29-32, civ) with concurrent radiotherapy (60 Gy/30 fr) followed by additional Cx (CDDP [80 mg/m²/day, day 1 and 29] and FU [800 mg/m²/day, days 1-5 and 29-33, civ]). Pts in arm B receive 3 courses of DCF (DOC [70 mg/m², day 1], CDDP [70 mg/m², day 1] and FU [750 mg/m², days 1–5] every 3 weeks) followed by CS if converted to be resectable, or dCRT same as Arm A if not converted to be resectable based on the radiological evaluation. Salvage surgery or endoscopic resection are acceptable in arm A (if residual, progressive, or recurring after dCRT) and in arm B (if converted to be resectable during or after dCRT). Primary endpoint is OS to confirm the superiority of arm B. We assumed 3-year OS with arm A to be 30% and expected a 12% increase for arm B. The planned sample size was calculated as a total of 230 pts (115 pts per arm) with a one-sided alpha of 5%, power of 70%, an accrual period of 4.5 years, and a follow-up period of 3 years. This trial was registered with UMIN-CTR, number UMIN000031165 and started in February 2018.

Clinical trial identification

UMIN000031165.

Legal entity responsible for the study

Japan Clinical Oncology Group: JCOG.

Funding

Japan Agency for Medical Research and Development (AMED).

Editorial Acknowledgement

Disclosure

H. Daiko, H. Ogawa, K. Hori, J. Mizusawa, S. Ozawa, M. Takagi, M. Tanaka, H. Baba, Y. Shirakawa, M. Tsuda, S. Nakagawa, H. Takeuchi, T. Abe, Y. Ito, T. Kadota, H. Fukuda: Japan Agency for Medical Research and Development (AMED), Ministry of Health, Labour and Welfare, Japan H. Hara: Japan Agency for Medical Research and Development (AMED), Ministry of Health, Labour and Welfare, Japan, Astrazeneca, Chugai, Merck Serono, MSD, Ono, Taiho, Takeda, Boehringer, Dainippon Sumitomo, Daiichi sankyo, Lilly, Pfizer, LSK Biopharma, Eisai, Incyte T. Kojima: Japan Agency for Medical Research and Development (AMED), Ministry of Health, Labour and Welfare, Japan, Shionogi, Ono, MSD, Oncolysis BioPharma, Astellas Amgen BioPharma K. Kato: Ono Pharmaceuticals, Merck and Co., Merck Serona, Shionogi Co and Ltd., Japan Agency for Medical Research and Development (AMED), Ministry of Health, Labour and Welfare, Japan Y. Kitagawa: Japan Agency for Medical Research and Development (AMED), Ministry of Health, Labour and Welfare, Japan, Kyowa hakko kirin, Takeda, Yakult honsya, Daiichi-sankyo.