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

Phase 2

Completed

• Conditions: Colorectal Cancer Stage IV; Metastasis
• Interventions: Drug: Cetuximab plus FOLFIRI/FOLFOX; Drug: FOLFIRI/FOLFOX/CapeOX

• Registration Number: NCT03031444
• Lead Sponsor: Peking University Cancer Hospital & Institute

Brief Summary

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

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.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-12-04
• Study First Submitted QC: 2017-01-23
• Study First Posted: 2017-01-25
• Primary Completion: 2020-12-30
• Study Completion: 2020-12-30
• Status Verified: 2021-01
• Last Update Submitted: 2021-01-29
• Last Update Posted: 2021-02-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 135

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
chemotherapy plus cetuximab	Cetuximab plus FOLFIRI/FOLFOX	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 \[Oxaliplatin 85 mg/m2 IV over 2 hours, day 1 Leucovorin 400 mg/m2 IV over 2 hours, day 1 5-FU 400 mg/m2 IV bolus on day 1, then 1200 mg/m2/day x 2 days (total 2400 mg/m2 over 46-48 hours) IV continuous infusion Repeat every 2 weeks;Cetuximab 500 mg/m2 IV over 2 hours, day 1, every 2 weeks\]
perioperative chemotherapy alone	FOLFIRI/FOLFOX/CapeOX	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.

Primary Outcome Measures

Name	Time	Method
disease free survival	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	months the patient lived from the date of liver resection to the date of disease recurrence or metastasis

Secondary Outcome Measures

Name	Time	Method
overall survival	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	months the patient lived from the date of liver resection to the date of patient death
objective response rate	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	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.

Trial Locations

Locations (4)

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

West China Hospital, Sichuan University; 🇨🇳 Chengdu, Sichuan, China

First Affiliated Hospital of Kunming Medical University; 🇨🇳 Kunming, Yunnan, China

Zhejiang Cancer Hospital; 🇨🇳 Hangzhou, Zhejiang, China