Perioperative Chemotherapy Plus Cetuximab Versus Chemotherapy Alone for High Risk Resectable Colorectal Liver Metastasis

Study Overview
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Brief Summary
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This study was designed to analyze the prognosis and recurrence predictive factors of high risk patients (Clinical Risk Score≥3) of resectable colorectal liver metastasis. The efficacy of perioperative chemotherapy plus cetuximab and chemotherapy alone was compared for these patients.

Detailed Description
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Resection could prolong the survival of colorectal liver metastasis patients, however,the curative resection rate was still low and more than 2/3 of the patients would experience tumor recurrence.This study was designed to formulate a more accurate and individual evaluation system via the multivariate analysis. Up to now, there was no data to demonstrate the addition of cetuximab to perioperative chemotherapy could decrease recurrence and prolong survival for RAS wild-type, high risk(Clinical Risk Score≥3) resectable colorectal liver metastasis patients. This study was also designed to elucidate this question and to observe the objective response rate(ORR) and the safety data of the regime.

Official Title
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A Multicenter Study of Prognosis and the Efficacy Comparison of Perioperative Chemotherapy Plus Cetuximab Versus Chemotherapy Alone for High Risk Patients(Clinical Risk Score≥3) of Resectable Colorectal Liver Metastasis

Conditions
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Colorectal Cancer Stage IV, Metastasis

Intervention / Treatment
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* Drug: Cetuximab plus FOLFIRI/FOLFOX
* Drug: FOLFIRI/FOLFOX/CapeOX


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: good performance status pathologic diagnosis of colorectal cancer Rat sarcoma viral oncogene homolog(RAS) wild-type radiologic confirmation the resectability of liver metastases enough future liver remnant Clinical Risk Score≥3 treatment naive extra-hepatic metastases could be resected completely, if exist Exclusion Criteria: poor performance status, could not tolerate chemotherapy or operation other malignancy history or synchronously extra-hepatic metastases could not be resected completely, if exist received other treatment previously

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: chemotherapy plus cetuximab<br>Cetuximab plus FOLFIRI/FOLFOX:FOLFIRI plus cetuximab [Irinotecan 180 mg/m2 IV over 30-90 minutes, day 1;Leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion, day 1;5-fluoruracil(5-FU) 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion.Repeat every 2 weeks.Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks] or FOLFOX plus Cetuximab [Oxaliplatin 85 mg/m2 IV over 2 hours, day 1 Leucovorin 400 mg/m2 IV over 2 hours, day 1 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion Repeat every 2 weeks;Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks] | Drug: Cetuximab plus FOLFIRI/FOLFOX<br>* cetuximab was added into the routine perioperative chemotherapy(FOLFIRI/FOLFOX) to evaluate its safety and efficacy<br>* Other names: C225;|
| Active Comparator: perioperative chemotherapy alone<br>FOLFIRI/FOLFOX/CapeOX:routine perioperative chemotherapy including FOLFIRI[Irinotecan 180 mg/m2 IV over 30-90 minutes, day 1 Leucovorin 400 mg/m2 IV infusion to match duration of irinotecan infusion, day 1 5-FU 400 mg/m2 IV bolus day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) continuous infusion Repeat every 2 weeks] or FOLFOX[Oxaliplatin 85 mg/m2 IV over 2 hours, day 1;Leucovorin 400 mg/m2 IV over 2 hours, day 1 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion Repeat every 2 weeks] or CapeOX[Oxaliplatin 130 mg/m2 IV over 2 hours, day 1 Capecitabine 850-1000mg/m2 twice daily PO for 14 days Repeat every 3 weeks] was adopted in this control arm. | Drug: FOLFIRI/FOLFOX/CapeOX<br>* to evaluate its safety and efficacy of routine perioperative chemotherapy(FOLFIRI/FOLFOX/CapeOX)<br>* Other names: XELOX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| disease free survival | months the patient lived from the date of liver resection to the date of disease recurrence or metastasis | From date of hepatectomy until the date of first documented recurrence or metastasis or date of death from any cause, whichever came first, assessed up to 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall survival | months the patient lived from the date of liver resection to the date of patient death | From date of hepatectomy until the date of first documented death from any cause or the last follow-up if no death happened, assessed up to 60 months | 
| objective response rate | percent of the number of patients who showed partial response(PR) or complete response(CR) who received preoperative chemotherapy to the number of all the patients enrolled. | from the date of the first chemotherapy until the date two weeks after the completion of the last preoperative chemotherapy, assessed up to 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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colorectal liver metastasis, preoperative, chemotherapy, targeted therapy