Consolidative Radiotherapy for Colorectal Cancer Liver Metastases Receiving Surgery or Radiofrequency Ablation

Study Overview
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Brief Summary
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This study is a randomized phase II trial to evaluate the efficacy of adjuvant consolidative radiotherapy in colorectal cancer liver metastasis (CRLM) patients after chemotherapy combined with surgical resection or radiofrequency ablation of liver lesions.

Detailed Description
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Liver metastases are detected in 40-50% of patients diagnosed with colorectal cancer. Local treatments like surgical resection or radiofrequency ablation result in 5-year survival of 35%. However, relapse still occurs in 70% of patients. Stereotactic body radiotherapy (SBRT) has emerged as a valid treatment not only to provide excellent symptom palliation, but also is effective in local control of metastatic lesions and improves survival. The potential efficacy of SBRT as adjuvant radiotherapy in CRLM patients after surgical resection or radiofrequency ablation is still unknown.

Official Title
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Consolidative Radiotherapy for Colorectal Cancer Liver Metastases Receiving Surgery or Radiofrequency Ablation

Conditions
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Radiotherapy, Colorectal Cancer, Liver Metastases

Intervention / Treatment
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* Radiation: adjuvant SBRT
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Biopsy proven unresectable metastatic colorectal cancer (CRC) Primary resection of colorectal cancer (CRC) Age≥18 years Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Absence of evidence of extra-hepatic diseases 1 to 3 liver metastases with an individual maximum diameter of up to 5 cm Metastatic liver lesions receiving R0 or R1 resection or radiofrequency ablation with visible tumor bed Aspartate aminotransferase, alanine aminotransferase & alkaline phosphates must be ≤ 2.5 times of the upper limit of normal. Total bilirubin must be within the limit of normal. Patients should have adequate bone marrow function as defined by peripheral granulocyte count of ≥1500/mm3. Patients must provide verbal and written informed consent to participate in the study. Absence of any severe pulmonary or cardiac diseases Exclusion Criteria: Patients with either untreated brain metastases or brain metastases treated within the past three months are ineligible Patients who are pregnant Patients with severe organ dysfunction History of liver radiotherapy Unwillingness to participate or inability to comply with the protocol for the duration of the study Participation in any investigational drug study within 3 months preceding the start of study treatment Patients not suitable to take part in clinical trials judged by researches

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Parallel Assignment
Interventional Model Description: adjuvant radiotherapy:SBRT chemotherapy:mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: chemoradiotherapy<br>radiotherapy: adjuvant SBRT of liver lesions; chemotherapy: mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment | Radiation: adjuvant SBRT<br>* adjuvant SBRT of liver lesions<br>* Other names: radiotherapy;Drug: Chemotherapy<br>* mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment<br>* Other names: neoadjuvant chemotherapy and adjuvant chemotherapy;|
| Active Comparator: chemotherapy<br>chemotherapy: mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment | Drug: Chemotherapy<br>* mFolfox6/ CAPEOX/ Folfiri±cetuximab or bevacizumab, 2 months for neoadjuvant treatment and 4 months for adjuvant treatment<br>* Other names: neoadjuvant chemotherapy and adjuvant chemotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease free survival | Evaluate the effect of consolidative SBRT of liver lesions versus observation on disease free survival | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | To evaluate overall survival after consolidative SBRT in comparison to observation alone | 5 years | 
| Intrahepatic disease free survival | To evaluate Intrahepatic disease free survival after consolidative SBRT in comparison to observation alone | 2 years | 
| Toxicities | Acute toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v3.0 criteria during and up to 3 months after radiotherapy. Late toxicity was graded using the Radiation Therapy Oncology Group (RTOG)/European Organisation for the Research and Treatment of Cancer (EORTC) criteria. | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, Colorectal Cancer, Liver Metastases