Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer
Open Access
- 13 April 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Cancer
- Vol. 11 (1), 134
- https://doi.org/10.1186/1471-2407-11-134
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 - NCT01027221Keywords
This publication has 28 references indexed in Scilit:
- The Efficacy of Radiotherapy Relies upon Induction of Type I Interferon–Dependent Innate and Adaptive ImmunityCancer Research, 2011
- The Tumor-Immune Microenvironment and Response to Radiation TherapyJournal of Mammary Gland Biology and Neoplasia, 2010
- Targeting inflammatory pathways for tumor radiosensitizationBiochemical Pharmacology, 2010
- Organ-, inflammation- and cancer specific transcriptional fingerprints of pancreatic and hepatic stellate cellsMolecular Cancer, 2010
- Chronic Pancreatitis Is Associated With Disease-Specific Regulatory T-Cell ResponsesGastroenterology, 2010
- MicroRNA expression after ionizing radiation in human endothelial cellsRadiation Oncology, 2010
- Antigen-specific Tregs control T cell responses against a limited repertoire of tumor antigens in patients with colorectal carcinomaJCI Insight, 2009
- Combination of Vascular Endothelial Growth Factor Receptor/Platelet-Derived Growth Factor Receptor Inhibition Markedly Improves Radiation Tumor TherapyClinical Cancer Research, 2008
- Pancreatic Stellate Cells: Partners in Crime with Pancreatic Cancer CellsCancer Research, 2008
- Transcriptional network governing the angiogenic switch in human pancreatic cancerProceedings of the National Academy of Sciences of the United States of America, 2007