Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer
<p>Abstract</p> <p>Background</p> <p>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 t...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2011-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | http://www.biomedcentral.com/1471-2407/11/134 |
| _version_ | 1818807705462112256 |
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| author | Debus Juergen Buechler Markus W Tjaden Christine Koch Moritz Rochet Nathalie Reissfelder Christoph Bonertz Andreas Roeder Falk FF Klug Felix Winnenthal Hubertus Timke Carmen Werner Jens Beckhove Philipp Weitz Jürgen Huber Peter E |
| author_facet | Debus Juergen Buechler Markus W Tjaden Christine Koch Moritz Rochet Nathalie Reissfelder Christoph Bonertz Andreas Roeder Falk FF Klug Felix Winnenthal Hubertus Timke Carmen Werner Jens Beckhove Philipp Weitz Jürgen Huber Peter E |
| author_sort | Debus Juergen |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods/Design</p> <p>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.</p> <p>Discussion</p> <p>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.</p> <p>Trial registration</p> <p>ClinicalTrials.gov - <a href="http://www.clinicaltrials.gov/ct2/show/NCT01027221">NCT01027221</a></p> |
| first_indexed | 2024-12-18T19:29:55Z |
| format | Article |
| id | doaj.art-48c2411738b8416aab0ed2227f9d3487 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-18T19:29:55Z |
| publishDate | 2011-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-48c2411738b8416aab0ed2227f9d34872022-12-21T20:55:45ZengBMCBMC Cancer1471-24072011-04-0111113410.1186/1471-2407-11-134Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancerDebus JuergenBuechler Markus WTjaden ChristineKoch MoritzRochet NathalieReissfelder ChristophBonertz AndreasRoeder Falk FFKlug FelixWinnenthal HubertusTimke CarmenWerner JensBeckhove PhilippWeitz JürgenHuber Peter E<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods/Design</p> <p>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.</p> <p>Discussion</p> <p>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.</p> <p>Trial registration</p> <p>ClinicalTrials.gov - <a href="http://www.clinicaltrials.gov/ct2/show/NCT01027221">NCT01027221</a></p>http://www.biomedcentral.com/1471-2407/11/134pancreatic cancerimmune therapylow dose radiationT-cells |
| spellingShingle | Debus Juergen Buechler Markus W Tjaden Christine Koch Moritz Rochet Nathalie Reissfelder Christoph Bonertz Andreas Roeder Falk FF Klug Felix Winnenthal Hubertus Timke Carmen Werner Jens Beckhove Philipp Weitz Jürgen Huber Peter E Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer BMC Cancer pancreatic cancer immune therapy low dose radiation T-cells |
| title | Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer |
| title_full | Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer |
| title_fullStr | Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer |
| title_full_unstemmed | Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer |
| title_short | Randomized controlled phase I/II study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer |
| title_sort | randomized controlled phase i ii study to investigate immune stimulatory effects by low dose radiotherapy in primarily operable pancreatic cancer |
| topic | pancreatic cancer immune therapy low dose radiation T-cells |
| url | http://www.biomedcentral.com/1471-2407/11/134 |
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