LOTCOL Study: Local Treatment of Colo-rectal Liver Met

Study Overview
=================
Brief Summary
-----------------
In this study the investigators will include colo-rectal cancer (CRC) patients starting last line of standard palliative chemotherapy. Eligible patients include patients with KRAS mutation starting line or KRAS wild type starting line treatment. Standard treatment today for these patients is chemotherapy only and median overall survival (OS) is about 10 months. The hypothesis is that local treatment in addition to systemic treatment will increase time to progression, progression free survival and overall survival compared to patients who receive systemic chemotherapy only. The investigators experience with local treatment of liver metastases in CRC patients is that side-effects of treatment in general are minor, although gastric bleeding have been observed after stereotactic body radiation therapy.

Official Title
-----------------
A Randomized Study With Palliative Chemotherapy With or Without Local Treatment of Liver Metastases in Patients With Colo-rectal Cancer

Conditions
-----------------
Metastatic Colo-rectal Cancer

Intervention / Treatment
-----------------
* Procedure: Radiofrequency ablation, microwave, radiation therapy
* Drug: Standard Chemotherapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologically verified adenocarcinoma of colon or rectum Ambulatory with an ECOG performance status 0-2 At least 18 years of age Non-resectable liver metastases Progressive disease on or within 4 months after 1.line chemotherapy for KRAS mutant or after 2.line chemotherapy in KRAS wild type patients 1-4 liver metastases with largest diameter of up to 6 cm on CT-scan Up to 20 lesions in liver with no more than 4 lesions larger than 4 cm The patients will start 2./3. line chemotherapy (KRAS mutant/KRAS wt) Laboratory values as the following: ANC ³ 1.5 x 109/L Platelets ³ 100 x 109/L Hb ³ 9g/dL Creatinine £ 2x upper limit of normal Bilirubin < 2.0x the upper limit of normal ASAT and ALAT £ 5x the upper limit of normal Albumin levels > 30 g/L INR<1.3 Signed informed consent and expected cooperation of the patients for the treatment and follow up must be obtained and documented according to ICH GCP, and national/local regulations Exclusion Criteria: Previous treatment with 2. or 3. line chemotherapy (KRAS mutant/KRAS wt) History of prior metastatic disease the last 3 years History of CNS or bone metastases Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia Largest liver mets >6 cm, more than 4 liver lesions >4 cm Pulmonary mets>3 cm Lymph node mets >2.5 cm Chemotherapy/radiation therapy or major surgery within the last 4 weeks before start of treatment Any reason why, in the opinion of the investigator, the patient should not participate.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cheomotherapy and local treatment<br>Standard chemotherapy + local treatment | Procedure: Radiofrequency ablation, microwave, radiation therapy<br>* Radiofrequency ablation Microwave ablation Radiation therapy<br>|
| Placebo Comparator: Cheomotherapy<br>Standard chemotherapy | Drug: Standard Chemotherapy<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival from time of randomization |  | 6 months |