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)

BMC Cancer. 2023 Jul 4;23(1):624. doi: 10.1186/s12885-023-11110-y.


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, .

Keywords: Clinical trial; Hyperthermia; Locally advanced pancreatic cancer; Multidisciplinary treatment; Proton beam therapy.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Albumins
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Gemcitabine
  • Humans
  • Hyperthermia, Induced*
  • Paclitaxel / therapeutic use
  • Pancreatic Neoplasms* / pathology
  • Protons


  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Gemcitabine
  • Paclitaxel
  • Protons