Low Dose Radiation to Improve T-Cell Infiltration in Pancreatic Cancer

Study Overview
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Brief Summary
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Principal purpose of the study is the determination of an active local external beam radiotherapy dose leading to a maximum number of tumor infiltrating T-cells.

Official Title
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Randomised Phase I/II Trial in Order to Evaluate the Effect of Neoadjuvant Radiation on Tumor Infiltrating T-cells by Neoadjuvant Low-Dose-Radiation Therapy in Primarily Resectable Pancreatic Cancer

Conditions
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Primarily Resectable Pancreatic Cancer

Intervention / Treatment
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* Radiation: neoadjuvant photon radiation
* Radiation: neoadjuvant photon radiation
* Radiation: neoadjuvant photon radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Radiological diagnosis of resectable pancreatic carcinoma is required prior to treatment. Potentially resectable is defined as no extrapancreatic disease, no evidence (on CT) of involvement of the celiac axis or superior mesenteric artery, no evidence (on CT or MRI) of occlusion of the superior mesenteric vein or superior mesenteric-portal venous confluence. No evidence of metastatic disease as determined by chest CT scan, abdominal CT scan (or MRI) 18 years of age or older American Society of Anesthesiologists (ASA)- Performance status of 1 to 3 Women of child bearing potential must practice adequate contraception and refrain from breast feeding. Female patients must have a negative pregnancy test within 7 days of treatment Informed consent Exclusion Criteria: Locally irresectable pancreatic cancer distant metastases medically unfit for surgery Pregnant or lactating women prior chemotherapy or radiation treatment Other serious uncontrolled medical conditions that the investigator feels might compromise study participation Unwillingness to participate or inability to comply with the protocol for the duration of the study Major surgery, excluding laparoscopy, within 4 weeks of the start of study treatment, without complete recovery Participation in other interventional trials

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 0<br>primarily resectable pancreatic cancer patients | |
| Active Comparator: 0,5 Gy<br>neoadjuvant Radiation of 0,5 Gy two days before resection | Radiation: neoadjuvant photon radiation<br>* single fraction, four dimensions (4D) planned, image guided, Radiation at a dose of 0,5 Gy in Intensity modulated radiotherapy (IMRT)-technique 2 days before resection<br>|
| Active Comparator: 2 Gy<br>neoadjuvant Radiation of 2 Gy 2 days before resection | Radiation: neoadjuvant photon radiation<br>* single fraction, 4D-planned, image guided, 2 Gy Radiation to the tumor with a safety margin, in IMRT-technique 2 days before resection<br>|
| Active Comparator: 5 Gy<br>neoadjuvant Radiation of 5 Gy 2 days before resection | Radiation: neoadjuvant photon radiation<br>* single fraction, 4D-planned, image guided, 5 Gy Radiation to the tumor with a safety margin, in IMRT-technique 2 days before resection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Principal purpose of the study is the determination of an active local external beam radiotherapy dose leading to a maximal number of tumor infiltrating T-cells. The total T-cell activity serves as primary surrogate parameters for anti- tumoral activity | Principal purpose of the study is the determination of an active local external beam radiotherapy dose leading to a maximal number of tumor infiltrating T-cells. The total T-cell activity serves as primary surrogate parameters for anti- tumoral activity | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| local control and recurrence patterns of pancreatic cancer relative to a standard as seen in historical controls | local control and recurrence patterns of pancreatic cancer relative to a standard as seen in historical controls | 5 years | 
| surgical morbidity in patients undergoing pancreatic resection who received this protocol treatment | surgical morbidity in patients undergoing pancreatic resection who received this protocol treatment | 1 year | 
| frequencies of tumor-reactive T-cells in blood and bone marrow | frequencies of tumor-reactive T-cells in blood and bone marrow | 2 years | 
| expression of migration-relevant adhesion molecules on tumor endothelial cells | expression of migration-relevant adhesion molecules on tumor endothelial cells | 2 years | 
| expression of proinflammatory cytokines and activation-dependent, immune-associated transcriptionally factors in tumors and blood | expression of proinflammatory cytokines and activation-dependent, immune-associated transcriptionally factors in tumors and blood | 2 years | 
| quality of life according to the EORTC QoL questionnaire after 6, 12, 18 and 24 months | quality of life according to the EORTC QoL questionnaire after 6, 12, 18 and 24 months | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Low Dose Radiation, pancreatic cancer, Immunostimulation