Durvalumab with or without tremelimumab combined with particle therapy for advanced hepatocellular carcinoma with macrovascular invasion: protocol for the DEPARTURE phase Ib trial.

Autor:	Ogasawara S; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan ogasawaras@chiba-u.jp.; Translational Research and Development Center, Chiba University Hospital, Chiba, Japan., Koroki K; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Makishima H; Department of Radiation Oncology, University of Tsukuba Hospital, Tsukuba, Japan., Wakatsuki M; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Takahashi A; Clinical Research Center, Chiba University Hospital, Chiba, Japan., Yumita S; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Nakagawa M; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Ishino T; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Ogawa K; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Fujiwara K; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Iwanaga T; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Sakuma T; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Fujita N; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Kojima R; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Kanzaki H; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Kobayashi K; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.; Translational Research and Development Center, Chiba University Hospital, Chiba, Japan., Kiyono S; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Nakamura M; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Kanogawa N; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Saito T; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Kondo T; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Nakagawa R; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Nakamoto S; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Muroyama R; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Chiba T; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan., Ozawa Y; Clinical Research Center, Chiba University Hospital, Chiba, Japan., Kawasaki Y; Clinical Research Center, Chiba University Hospital, Chiba, Japan., Kurokawa T; Clinical Research Center, Chiba University Hospital, Chiba, Japan., Hanaoka H; Clinical Research Center, Chiba University Hospital, Chiba, Japan., Tsuji H; National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan., Kato N; Department of Gastroenterology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Jazyk:	angličtina
Zdroj:	BMJ open [BMJ Open] 2022 Apr 08; Vol. 12 (4), pp. e059779. Date of Electronic Publication: 2022 Apr 08.
DOI:	10.1136/bmjopen-2021-059779
Abstrakt:	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. Competing Interests: Competing interests: SO has received honoraria from Bayer, Eisai, Eli Lilly and Chugai Pharma and research funding from Bayer, Eisai, Eli Lilly and AstraZeneca. NK has received honoraria from Bayer, Eisai, Eli Lilly and Chugai Pharma and research funding from Bayer, Eisai and Eli Lilly. (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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