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

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

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.

Study Overview

• Status: Unknown
• Conditions: Colorectal Liver Metastases
• Intervention / Treatment: Radiation: one time radiation; Radiation: No Radiation

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Germany
  • Heidelberg, Germany, 69120
    • Recruiting
    • University of Heidelberg
    • Contact: Juergen Weitz; Phone Number: +49 6221 56 6250; Email: juergen.weitz@med.uni-heidelberg.de
    • Contact: Christoph Reissfelder; Phone Number: +49 6221 56 6250; Email: christoph.reissfelder@med.uni-heidelberg.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Radiation 0,5Gy; 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; 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
Active Comparator: No radiation; Control group with 0Gy radiation	Radiation: No Radiation; Control group with 0Gy
Active Comparator: Radiation 2Gy; 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; 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
Active Comparator: Radiation 5Gy; Radiation: one time Radiation with an intensity of 5 Gy Group C Beginning on a weekday 48 hours before surgery	Radiation: one time radiation; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Heidelberg University

Publications and helpful links

General Publications

• Reissfelder C, Timke C, Schmitz-Winnenthal H, Rahbari NN, Koch M, Klug F, Roeder F, Edler L, Debus J, Buchler MW, Beckhove P, Huber PE, Weitz J. A randomized controlled trial to investigate the influence of low dose radiotherapy on immune stimulatory effects in liver metastases of colorectal cancer. BMC Cancer. 2011 Sep 30;11:419. doi: 10.1186/1471-2407-11-419.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Anticipated): March 1, 2012
• Study Completion (Anticipated): March 1, 2012

Study Registration Dates

• First Submitted: August 20, 2010
• First Submitted That Met QC Criteria: August 30, 2010
• First Posted (Estimate): August 31, 2010

Study Record Updates

• Last Update Posted (Estimate): October 22, 2010
• Last Update Submitted That Met QC Criteria: October 21, 2010
• Last Verified: October 1, 2010

More Information

Terms related to this study

• Keywords: surgery; radiation; T cell
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Liver Diseases; Neoplastic Processes; Neoplasm Metastasis; Liver Neoplasms
• Other Study ID Numbers: S081/2008