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

Sponsor

Heidelberg University (Other)

Overall Status

Unknown status

CT.gov ID

NCT01191632

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colorectal Liver Metastases	Radiation: one time radiation Radiation: No Radiation	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Mar 1, 2010

Anticipated Primary Completion Date :

Mar 1, 2012

Anticipated Study Completion Date :

Mar 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Heidelberg	Heidelberg		Germany	69120

Sponsors and Collaborators

Heidelberg University

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

, ,

ClinicalTrials.gov Identifier:

NCT01191632

Other Study ID Numbers:

S081/2008

First Posted:

Aug 31, 2010

Last Update Posted:

Oct 22, 2010

Last Verified:

Oct 1, 2010

Keywords provided by , ,

T cell

surgery

radiation

Additional relevant MeSH terms:

Neoplasm Metastasis

Liver Neoplasms

Study Results

No Results Posted as of Oct 22, 2010