Triple modal treatment comprising with proton beam radiation, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer: a phase I/II study protocol (TT-LAP trial)
Osamu Shimomura,
Masato Endo,
Hirokazu Makishima,
Takeshi Yamada,
Shinji Hashimoto,
Haruko Numajiri,
Yoshihiro Miyazaki,
Manami Doi,
Kinji Furuya,
Kazuhiro Takahashi,
Toshikazu Moriwaki,
Naoyuki Hasegawa,
Yoshiyuki Yamamoto,
Yusuke Niisato,
Mariko Kobayashi,
Masashi Mizumoto,
Kei Nakai,
Takashi Saito,
Sodai Hoshiai,
Tsukasa Saida,
Bryan J. Mathis,
Kensaku Mori,
Takahito Nakajima,
Kiichiro Tsuchiya,
Hideyuki Sakurai,
Tatsuya Oda
Affiliations
Osamu Shimomura
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba
Masato Endo
Department of Gastroenterology, University of Tsukuba
Hirokazu Makishima
Department of Radiation oncology, University of Tsukuba
Takeshi Yamada
Department of Gastroenterology, University of Tsukuba
Shinji Hashimoto
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba
Haruko Numajiri
Department of Radiation oncology, University of Tsukuba
Yoshihiro Miyazaki
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba
Manami Doi
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba
Kinji Furuya
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba
Kazuhiro Takahashi
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba
Toshikazu Moriwaki
Department of Gastroenterology, University of Tsukuba
Naoyuki Hasegawa
Department of Gastroenterology, University of Tsukuba
Yoshiyuki Yamamoto
Department of Gastroenterology, University of Tsukuba
Yusuke Niisato
Department of Gastroenterology, University of Tsukuba
Mariko Kobayashi
Department of Gastroenterology, University of Tsukuba
Masashi Mizumoto
Department of Radiation oncology, University of Tsukuba
Kei Nakai
Department of Radiation oncology, University of Tsukuba
Takashi Saito
Department of Radiation oncology, University of Tsukuba
Sodai Hoshiai
Department of Radiology, University of Tsukuba
Tsukasa Saida
Department of Radiology, University of Tsukuba
Bryan J. Mathis
International Medical Center, University of Tsukuba Hospital
Kensaku Mori
Department of Radiology, University of Tsukuba
Takahito Nakajima
Department of Radiology, University of Tsukuba
Kiichiro Tsuchiya
Department of Gastroenterology, University of Tsukuba
Hideyuki Sakurai
Department of Radiation oncology, University of Tsukuba
Tatsuya Oda
Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba
Abstract Background Locally advanced pancreatic ductal adenocarcinoma (PDAC), accounting for about 30% of PDAC patients, is difficult to cure by radical resection or systemic chemotherapy alone. A multidisciplinary strategy is required and our TT-LAP trial aims to evaluate whether triple-modal treatment with proton beam therapy (PBT), hyperthermia, and gemcitabine plus nab-paclitaxel is a safe and synergistically effective treatment for patients with locally advanced PDAC. Methods This trial is an interventional, open-label, non-randomized, single-center, single-arm phase I/II clinical trial organized and sponsored by the University of Tsukuba. Eligible patients who are diagnosed with locally advanced pancreatic cancer, including both borderline resectable (BR) and unresectable locally advanced (UR-LA) patients, and selected according to the inclusion and exclusion criteria will receive triple-modal treatment consisting of chemotherapy, hyperthermia, and proton beam radiation. Treatment induction will include 2 cycles of chemotherapy (gemcitabine plus nab-paclitaxel), proton beam therapy, and 6 total sessions of hyperthermia therapy. The initial 5 patients will move to phase II after adverse events are verified by a monitoring committee and safety is ensured. The primary endpoint is 2-year survival rate while secondary endpoints include adverse event rate, treatment completion rate, response rate, progression-free survival, overall survival, resection rate, pathologic response rate, and R0 (no pathologic cancer remnants) rate. The target sample size is set at 30 cases. Discussion The TT-LAP trial is the first to evaluate the safety and effectiveness (phases1/2) of triple-modal treatment comprised of proton beam therapy, hyperthermia, and gemcitabine/nab-paclitaxel for locally advanced pancreatic cancer. Ethics and dissemination This protocol was approved by the Tsukuba University Clinical Research Review Board (reference number TCRB22-007). Results will be analyzed after study recruitment and follow-up are completed. Results will be presented at international meetings of interest in pancreatic cancer plus gastrointestinal, hepatobiliary, and pancreatic surgeries and published in peer-reviewed journals. Trial registration Japan Registry of Clinical Trials, jRCTs031220160. Registered 24 th June 2022, https://jrct.niph.go.jp/en-latest-detail/jRCTs031220160 .
