Effect of Neoadjuvant Radiation on Tumor Infiltrating T-cells by Low Dose Radiation in Colorectal Liver Metastases

Study Overview
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Brief Summary
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The efficiency of T cell based immunotherapies is affected by the insufficient migration and activity of tumor specific effector T cells in the tumor. Aim of this phase I/II clinical trial is to evaluate whether a neoadjuvant, low dose radiotherapy can improve T cell connected anti tumor immune response in colorectal liver metastases. The primary endpoint is the number of tumor infiltrating T cells. Furthermore the T cell activity in situ, the number of regulatory T cells and the frequency of tumor reactive T cells in the blood and bone marrow will be examined.

Official Title
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Randomised Controlled Phase I/II Trail to Evaluate the Effect of Neoadjuvant Radiation on Tumor Infiltrating T-cells by Low Dose Radiation Therapy in Resectable Colorectal Liver Metastases Patients

Conditions
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Colorectal Liver Metastases

Intervention / Treatment
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* Radiation: one time radiation
* Radiation: No Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability of subject to understand character and individual consequences of the clinical trial Written informed consent (must be available before enrolment in the trial) Age ≥ 50 years Radiological urgently suspected colorectal liver metastasis Exclusion Criteria: second malignancy Pregnancy and lactation no prior liver radiation liver metastasis must be resectable

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Radiation 0,5Gy<br>Radiation: one time Radiation with an intensity of 0.5 Gy Group A Beginning on a weekday 48 hours before surgery | Radiation: one time radiation<br>* Radiation: one time Radiation with an intensity of 0.5 Gy Group A 2.0 Gy Group B 5 Gy Group C Beginning on a weekday 48 hours before surgery<br>|
| Active Comparator: No radiation<br>Control group with 0Gy radiation | Radiation: No Radiation<br>* Control group with 0Gy<br>|
| Active Comparator: Radiation 2Gy<br>Radiation: one time Radiation with an intensity of 2.0 Gy Group B Beginning on a weekday 48 hours before surgery | Radiation: one time radiation<br>* Radiation: one time Radiation with an intensity of 0.5 Gy Group A 2.0 Gy Group B 5 Gy Group C Beginning on a weekday 48 hours before surgery<br>|
| Active Comparator: Radiation 5Gy<br>Radiation: one time Radiation with an intensity of 5 Gy Group C Beginning on a weekday 48 hours before surgery | Radiation: one time radiation<br>* Radiation: one time Radiation with an intensity of 0.5 Gy Group A 2.0 Gy Group B 5 Gy Group C Beginning on a weekday 48 hours before surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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- tumor activity |  | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine local control and recurrence patterns of colorectal liver metastases in a CT |  | 2 years | 
| To determine the progression-free survival in patients treated with low dose photon beam radiation therapy |  | 2 years | 
| • To determine the surgical morbidity in patients undergoing liver resection who received this protocol treatment |  | 2 years | 
| • To determine 30-day post-operative mortality after liver resection in patients who received this protocol treatment |  | 2 years | 
| • To determine the T-cell activity in the resected liver tissue |  | 2 years | 
| • To determine quality of life according to the EORTC QoL questionnaire after 6 months. |  | 6 months | 
| To determine the number of regulatory T-cells in the resected liver tissue |  | 2 years | 
| To determine the frequencies of tumor-reactive T-cells in the blood and bone marrow of the patients |  | 2 years | 
| To determine quality of life according to the EORTC QoL questionnaire after 12 months. |  | 1 year | 
| To determine the number of patients with adverse events as a measure of safety and tolerability according to CTCAE, Version 4.0 criteria |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T cell, surgery, radiation