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Open Access Study protocol

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

Carmen Timke1, Hubertus Schmitz Winnenthal2, Felix Klug3, Falk FF Roeder1, Andreas Bonertz3, Christoph Reissfelder2, Nathalie Rochet1, Moritz Koch2, Christine Tjaden2, Markus W Buechler2, Juergen Debus1, Jens Werner2, Philipp Beckhove3, Jürgen Weitz2 and Peter E Huber1*

Author Affiliations

1 Department of Radiation Oncology, German Cancer Research Center and University Hospital Center, Heidelberg, Germany

2 Department of General, Visceral and Transplantation Surgery, University Hospital Center Heidelberg, Germany

3 Translational Immunology Unit, German Cancer Research Center, Heidelberg, Germany

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BMC Cancer 2011, 11:134  doi:10.1186/1471-2407-11-134

Published: 13 April 2011

Abstract

Background

The 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/Design

This 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.

Discussion

This 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 registration

ClinicalTrials.gov - NCT01027221

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