Chemotherapy With Cetuximab as Conversion Therapy in RAS/BRAF WT Unresectable Liver Metastasis Right-sided Colon Cancer

Doublet or Triplet Chemotherapy With Cetuximab as Conversion Therapy in RAS/BRAF Wild Type Unresectable Liver Metastasis Right-sided Colon Cancer With Curative Intent：Multi-center, Ambispective Observational Trial

This study was designed as multi-center, ambispective observational trial to evaluate the efficacy and safety of addition of cetuximab to doublet or triplet chemotherapy as conversion therapy in right-sided BRAF/RAS wild-type CRLM with curative intent. The primary endpoint was radical resection rate (R0). The secondary endpoint was response rate, rate of NED, depth of remission, early tumor shrinkage, progression free survival and safety.

Study Overview

• Status: Recruiting
• Conditions: Colon Cancer
• Intervention / Treatment: Drug: Doublet or triplet chemotherapy combined with cetuximab

Detailed Description

Patients with colorectal liver-limited metastases (CLM) represent an exceptional subgroup with regards to the possible benefits of potentially curative multidisciplinary strategies, in which the upfront most active combination regimens are preferred to improve the rate of radical resection (R0) and NED (no evidence of disease). Unfortunately, Data are limited that specifically address the tumor location's impact on conversion therapy. As far as right-sided CRLM are concerned, much lower R0 after conversion therapy could be achieved when compared with left-sided CRLM. Furthermore, great controversies remain about the optimal conversion regimens in right-sided CRLM and the potential roles of anti-EGFR with regards to the different recommendations from NCCN, ESMO and CSCO guidelines. Chemotherapy plus cetuximab have the advantages in terms of response rate, early tumor shrinkage and depth of response, thus it is still of great value to explore the roles of cetuximab plus chemotherapy as conversion strategy in the right-sided RAS/BRAF wild type and MSS CRLM in the real world scenario.

This study was designed as multi-center, ambispective observational trial to evaluate the efficacy and safety of addition of cetuximab to doublet or triplet chemotherapy as conversion therapy in right-sided BRAF/RAS wild-type CRLM with curative intent. The primary endpoint was radical resection rate (R0). The secondary endpoint was response rate, rate of NED, depth of remission, early tumor shrinkage, progression free survival and safety.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Jing Hao, PhD; Phone Number: 18560082857; Email: hedi0084@hotmail.com

Study Locations

• China
  • Shandong
    • Jinan, Shandong, China, 250012
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: xiangling Wang, Dr.; Phone Number: 8653182169841; Email: xlwang71@163.com
      • Principal Investigator: Jing Hao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

RAS/BRAF wild type unresectable liver metastasis right-sided colon cancer

Description

Inclusion Criteria:

• Signed informed consent obtained before any study specific procedures. Subjects must be able to understand and willing to sign a written informed consent;
• Male or female subjects > 18 years < 75 of age;
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 ;
• Life expectancy of more than 3 months;
• Patients with pathologically confirmed metastatic colorectal liver metastases with molecular testing RAS/BRAF wild-type, MSS;
• At least one measurable lesion in liver metastases according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1;
• No previous any systemic anticancer therapy; if received primary tumor surgery and postoperative adjuvant chemotherapy, more than 6 months from the end of the last chemotherapy;
• Liver metastases are initially unresectable, but can have the opportunity to achieve complete resection or NED status with conversion therapy;
• Patients have adequate bone marrow, hepatic and renal function;

Exclusion Criteria:

• Any evidence of extra-hepatic metastases, lymph node (including portal lymph nodes) metastases and primary tumor recurrence.
• The primary tumor cannot be completely resected;
• If the possibility of R0 transformation is achieved, the patient refuses surgery due to non-medical factors.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Doublet or triplet chemotherapy combined with cetuximab

Drug: Doublet or triplet chemotherapy combined with cetuximab; chemotherapy+cetuximab combination therapy，chemotherapy regimens include FOLFOX, FOLFIRI, XELOX, or mFOLFOXIRI. Cetuximab first dose 400 mg/m2, followed by cetuximab 250 mg/m2 every 2 weeks; mFOLFOX6: oxaliplatin 85 mg/m2 (day 1), 5-FU 400 mg/m2 (day 1), LV 400 mg/m2 (day 1), and 5-FU 2400 mg/m2 CIV (46 h) for up to 12 cycles; XELOX (biweekly): oxaliplatin 85 mg/m2 (day 1), capecitabine 1000 mg/m2, bid, d1-10; FOLFIRI: irinotecan 180 mg/m2 (day 1), 5-FU 400 mg/m2 (day 1), LV 400 mg/m2 (day 1), and 5-FU 2400 mg/m2 CIV (46 h), Up to 12 cycles; mFOLFOXIRI: oxaliplatin 85 mg/m2 (day 1), irinotecan 150 mg/m2 (day 1), 5-FU 400 mg/m2 (day 1), LV 400 mg/m2 (day 1) and 5-FU 2400 mg/m2 CIV (46 h).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 resection rate	R0 resection rate upon conversion treatment with chemotherapy plus cetuximab	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Time from date of randomization until the date of first documented progression or date of death from any cause, whichever came first.	2 year
Objective response rate	CR + PR rate according to RECIST	1 year
Reported adverse events	Number of patients with adverse events and severity according to NCI CTC 4.0	1 year
no evidence of disease	the percentage of patients who had a curative liver treatment following protocol treatment	1 year
depth of response	DOR means that the period from the day when either CR or PR is first confirmed until the day of documented PD or the day of death due to all causes, whichever occurs earlier.	1 year
Early Tumor Shrinkage	Early tumor shrinkage assessed by Response rate at week 8	1 year

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2025

Study Registration Dates

• First Submitted: March 6, 2024
• First Submitted That Met QC Criteria: March 13, 2024
• First Posted (Actual): March 20, 2024

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: KYLL-202304-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No