Durvalumab with or without tremelimumab combined with particle therapy for advanced hepatocellular carcinoma with macrovascular invasion: protocol for the DEPARTURE phase Ib trial
Masato Nakamura,
Takayuki Kondo,
Yohei Kawasaki,
Hideki Hanaoka,
Naoya Kato,
Sadahisa Ogasawara,
Keisuke Koroki,
Hirokazu Makishima,
Masaru Wakatsuki,
Asahi Takahashi,
Sae Yumita,
Miyuki Nakagawa,
Takamasa Ishino,
Keita Ogawa,
Kisako Fujiwara,
Terunao Iwanaga,
Takafumi Sakuma,
Naoto Fujita,
Ryuta Kojima,
Hiroaki Kanzaki,
Kazufumi Kobayashi,
Soichiro Kiyono,
Naoya Kanogawa,
Tomoko Saito,
Ryo Nakagawa,
Shingo Nakamoto,
Ryosuke Muroyama,
Tetsuhiro Chiba,
Yoshihito Ozawa,
Tomoya Kurokawa,
Hiroshi Tsuji
Affiliations
Masato Nakamura
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Takayuki Kondo
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Yohei Kawasaki
Biostatistics Section, Clinical Research Centre, Chiba University Hospital, Chiba, Japan
Hideki Hanaoka
5 Clinical Research Center, Chiba University Hospital, Chiba, Japan
Naoya Kato
3 Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan
Sadahisa Ogasawara
Translational Research and Development Center, Chiba University Hospital, Chiba, Japan
Keisuke Koroki
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Hirokazu Makishima
Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba, Japan
Masaru Wakatsuki
National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan
Asahi Takahashi
Clinical Research Center, Chiba University Hospital, Chiba, Japan
Sae Yumita
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Miyuki Nakagawa
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Takamasa Ishino
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Keita Ogawa
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Kisako Fujiwara
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Terunao Iwanaga
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Takafumi Sakuma
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Naoto Fujita
Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic bomb Survivors Hospital, Hiroshima, Japan
Ryuta Kojima
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Hiroaki Kanzaki
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Kazufumi Kobayashi
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Soichiro Kiyono
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Naoya Kanogawa
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Tomoko Saito
2Institute of Immunology Co., Ltd., Tokyo, Japan
Ryo Nakagawa
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Shingo Nakamoto
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Ryosuke Muroyama
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Tetsuhiro Chiba
Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan
Yoshihito Ozawa
Biostatistics Section, Clinical Research Center, Chiba University Hospital, Chiba, Chiba, Japan
Tomoya Kurokawa
Clinical Research Center, Chiba University Hospital, Chiba, Japan
Hiroshi Tsuji
1 Department of Neurology, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
Introduction Advanced hepatocellular carcinoma (HCC) with macrovascular invasion (MVI) has the worst prognosis among all phenotypes. This trial aims to evaluate whether treatment with durvalumab, alone or in combination with tremelimumab, plus particle therapy is a safe and synergistically effective treatment in patients with advanced HCC and MVI.Methods and analysis This phase Ib, multicentre (two sites in Japan), open-label, single-arm, investigator-initiated clinical trial will assess durvalumab monotherapy in combination with particle therapy (cohort A) and that of durvalumab plus tremelimumab in combination with particle therapy (cohort B) for patients with advanced HCC with MVI. Cohort A will receive 1500 mg durvalumab every 4 weeks. Cohort B will receive 1500 mg durvalumab every 4 weeks in principle and 300 mg tremelimumab only on day 1 of the first cycle. Carbon-ion radiotherapy will be administered after day 8 of the first cycle. The primary endpoints are rates of any and severe adverse events, including dose-limiting toxicities (DLTs); secondary endpoints are overall survival, 6-month survival, objective response, 6-month progression-free survival and time to progression. Patients are initially enrolled into cohort A. If cohort A treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), the trial proceeds to enrol more patients into cohort B. Similarly, if cohort B treatment is confirmed to be tolerated (ie, no DLT in three patients or one DLT in six patients), a total of 15 patients will be enrolled into cohort B.Ethics and dissemination This study was approved by the ethics committees of the two participating institutions (Chiba University Hospital and National Institutes for Quantum (approval number: 2020040) and Radiological Science and Technology, QST Hospital (approval number: C20-001)). Participants will be required to provide written informed consent. Trial results will be reported in a peer-reviewed journal publication.Trial registration number jRCT2031210046.
