Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer

BMC Cancer

Study Protocol

Christoph Reissfelder¹  Moritz Koch¹  Christine Tjaden¹  Jens Werner¹  Markus W Buechler¹  Hubertus Schmitz Winnenthal¹  Jürgen Weitz¹  Nathalie Rochet²  Falk FF Roeder²  Carmen Timke²  Peter E Huber²  Juergen Debus²  Andreas Bonertz³  Felix Klug³  Philipp Beckhove³ 

[1] Department of General, Visceral and Transplantation Surgery, University Hospital Center Heidelberg, Germany;Department of Radiation Oncology, German Cancer Research Center and University Hospital Center, Heidelberg, Germany;Translational Immunology Unit, German Cancer Research Center, Heidelberg, Germany;

关键词: pancreatic cancer;    immune therapy;    low dose radiation;    T-cells;   

DOI  :  10.1186/1471-2407-11-134

 received in 2011-02-24, accepted in 2011-04-13,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe efficiencies of T cell based immunotherapies are affected by insufficient migration and activation of tumor specific effector T cells in the tumor. Accumulating evidence exists on the ability of ionizing radiation to modify the tumor microenvironment and generate inflammation. The aim of this phase I/II clinical trial is to evaluate whether low dose single fraction radiotherapy can improve T cell associated antitumor immune response in patients with pancreatic cancer.Methods/DesignThis trial has been designed as an investigator initiated; prospective randomised, 4-armed, controlled Phase I/II trial. Patients who are candidates for resection of pancreatic cancer will be randomized into 4 arms. A total of 40 patients will be enrolled. The patients receive 0 Gy, 0.5 Gy, 2 Gy or 5 Gy radiation precisely targeted to their pancreatic carcinoma. Radiation will be delivered by external beam radiotherapy using a 6 MV Linac with IMRT technique 48 h prior to the surgical resection. The primary objective is the determination of an active local external beam radiation dose, leading to tumor infiltrating T cells as a surrogate parameter for antitumor activity. Secondary objectives include local tumor control and recurrence patterns, survival, radiogenic treatment toxicity and postoperative morbidity and mortality, as well as quality of life. Further, frequencies of tumor reactive T cells in blood and bone marrow as well as whole blood cell transcriptomics and plasma-proteomics will be correlated with clinical outcome. An interim analysis will be performed after the enrolment of 20 patients for safety reasons. The evaluation of the primary endpoint will start four weeks after the last patient's enrolment.DiscussionThis trial will answer the question whether a low dose radiotherapy localized to the pancreatic tumor only can increase the number of tumor infiltrating T cells and thus potentially enhance the antitumor immune response. The study will also investigate the prognostic and predictive value of radiation-induced T cell activity along with transcriptomic and proteomic data with respect to clinical outcome.Trial registrationClinicalTrials.gov - NCT01027221

【 授权许可】

Unknown   
© Timke et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.