Clinical trial NCT01191632: Effect of Neoadjuvant Radiation on Tumor Infiltrating T-cells by Low Dose Radiation in Colorectal Liver Metastases
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Colorectal Liver Metastases
Keywords: T cell
surgery
radiation
Lead sponsor: Heidelberg University
Sponsor class: OTHER
First posted: 2010-08-31
Enrollment: 40
Sex: ALL
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 2 years
Secondary outcomes:
measure: To determine local control and recurrence patterns of colorectal liver metastases in a CT
timeFrame: 2 years
measure: To determine the progression-free survival in patients treated with low dose photon beam radiation therapy
timeFrame: 2 years
measure: • To determine the surgical morbidity in patients undergoing liver resection who received this protocol treatment
timeFrame: 2 years
measure: • To determine 30-day post-operative mortality after liver resection in patients who received this protocol treatment
timeFrame: 2 years
measure: • To determine the T-cell activity in the resected liver tissue
timeFrame: 2 years
measure: • To determine quality of life according to the EORTC QoL questionnaire after 6 months.
timeFrame: 6 months
measure: To determine the number of regulatory T-cells in the resected liver tissue
timeFrame: 2 years
measure: To determine the frequencies of tumor-reactive T-cells in the blood and bone marrow of the patients
timeFrame: 2 years
measure: To determine quality of life according to the EORTC QoL questionnaire after 12 months.
timeFrame: 1 year
measure: To determine the number of patients with adverse events as a measure of safety and tolerability according to CTCAE, Version 4.0 criteria
timeFrame: 2 years
Other outcomes:
Locations:
city: Heidelberg
country: Germany
facility: University of Heidelberg
Study officials:
References:
citation: 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.