Study protocol for a multi-institutional randomized phase III study comparing combined everolimus plus lanreotide therapy and everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic neuroendocrine tumors; Japan Clinical Oncology Group Study JCOG1901 (STARTER-NET study).

Everolimus is recognized as one of the standard drugs for the treatment of unresectable or recurrent gastroenteropancreatic neuroendocrine tumors (NET). However, recent evidence has suggested that addition of somatostatin analogs to everolimus may yield better survival outcomes as compared to everolimus alone. In April 2020, we have initiated a randomized phase III trial in Japan, to confirm the superiority of combined everolimus plus lanreotide therapy over everolimus monotherapy in patients with unresectable or recurrent gastroenteropancreatic NETs with poor prognostic factors (Ki-67 labeling index: LI 5%-20% or Ki-67 LI < 5% with diffuse liver metastases). We plan to enroll a total of 250 patients from 76 institutions over an accrual period of 5 years. The primary endpoint is progression-free survival. The key secondary endpoint is overall survival, with response rate, disease control rate, and proportion of patients with adverse events as the other secondary endpoints. This trial is registered with the Japan Registry of Clinical Trials as jRCT1031200023 [https://jrct.niph.go.jp/en-latest-detail/jRCT1031200023].

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Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest Dr. Shimoyama reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; Dr. Hijioka reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; personal fees from Pfizer, personal fees from Novartis, personal fees from Teijin Pharma, personal fees from Nobel Pharma, personal fees from AstraZeneca, personal fees from Otsuka Pharma, personal fees from Fujifilm Toyama Chemical Co. outside the submitted work; Dr. Mizuno reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; grants and personal fees from Taiho Pharmaceutical, grants from AstraZeneca, grants from NanoCarrier, grants from Eisai, grants and personal fees from MSD, grants from Dainippon Sumitomo Pharma, grants from ASLAN Pharmaceuticals, grants from Incyte, grants and personal fees from Yakult Honsha, grants from ONO Pharmaceutical, grants and personal fees from Novartis, personal fees from Teijin Pharma, outside the submitted work; Dr. Ogawa reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; Dr. Kataoka reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; Dr. Katayama reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; personal fees from Johnson & Johnson, outside the submitted work; Dr. Machida reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; grants and personal fees from MSD K.K., personal fees from ONO Pharmaceutical Co., Ltd., personal fees from Taiho Pharmaceutical Co., Ltd., personal fees from Bristol-Myers Squibb K.K., personal fees from Daiichi Sankyo Co., Ltd., personal fees from Yakult Honsha Co., Ltd., personal fees from Eli Lilly Japan K.K., personal fees from Teijin Pharma Ltd., outside the submitted work; Dr. Honma reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; grants and personal fees from Merck Biopharma, grants and personal fees from Novartis Pharma, grants and personal fees from Teijin Pharma, grants and personal fees from Chugai Pharma, grants from Taiho Pharma, personal fees from Ono Pharma, personal fees from Bristol Meyers Squibb, outside the submitted work; Dr. Boku reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; grants and personal fees from Ono, grants and personal fees from Taiho, personal fees from Bristol-Myers Squibb, grants from Takeda, outside the submitted work; Dr. Hamaguchi reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; grants and personal fees from Taiho, grants from Eisai, grants and personal fees from Chugai, grants and personal fees from Ono, personal fees from Merck, personal fees from Takeda, personal fees from Novartis, personal fees from Yakult, personal fees from Sanofi, personal fees from Bristol Meyers, personal fees from Bayer, personal fees from Fuji film, personal fees from Nippon Kayaku, personal fees from Daiichi Sankyo, outside the submitted work; Dr. Fukuda reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; Dr. Terashima reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; personal fees from Taiho, personal fees from Chugai, personal fees from Ono, personal fees from BMS, personal fees from Yakult, personal fees from Takeda, personal fees from Eli Lilly, personal fees from Pfizer, personal fees from Daiichi Sankyo, outside the submitted work; Dr. Kanemitsu reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; personal fees from Johnson & Johnson K.K., personal fees from Chugai Pharmaceutical Co., Ltd., personal fees from Kaken Pharmaceutical Co., Ltd, personal fees from Covidien Japan Inc, personal fees from Taiho Pharmaceutical Co., Ltd, personal fees from Intuitive Surgical, Inc., personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Taiho Pharmaceutical Co., Ltd, outside the submitted work; Dr. Furuse reports grants from Ministry of Health, Labour and Welfare, Japan, during the conduct of the study; grants and personal fees from Ono Pharmaceutical, grants and personal fees from MSD, grants and personal fees from Sumitomo Dainippon, grants from J-Pharma, grants and personal fees from Yakult Honsha, grants from AstraZeneca, grants and personal fees from Daiichi Sankyo, grants and personal fees from Eisai, grants from Bayer, grants and personal fees from Pfizer, grants from NanoCarrier, grants and personal fees from Kyowa Hakko Kirin, grants from Taiho Pharmaceutical, grants and personal fees from Chugai Pharma, grants and personal fees from Sanofi, grants and personal fees from Takeda, grants and personal fees from Mochida Pharmaceutical, grants from Astellas Pharma, grants and personal fees from Eli Lilly Japan, personal fees from Bayer Yakuhin, personal fees from Taiho Pharmaceutical, personal fees from Novartis, personal fees from Teijin Pharma, personal fees from Shionogi, personal fees from EA pharma, personal fees from Nihon Servier, personal fees from Fujifilm Toyama Chemical Co., personal fees from Nobel pharma, personal fees from Sawai Pharmaceutical, personal fees from Merck Serono, personal fees from Nippon Kayaku, personal fees from Shire, outside the submitted work.