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

NCT ID: NCT06322147

Last Updated: 2024-03-20

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 50 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2025-12-30

Brief Summary

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.

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.

Conditions

Colon Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

Doublet or triplet chemotherapy combined with cetuximab

Doublet or triplet chemotherapy combined with cetuximab

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Qilu Hospital of Shandong University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Qilu hospital of Shandong University

Jinan, Shandong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Jing Hao, PhD

Role: CONTACT

hedi0084@hotmail.com

18560082857

Facility Contacts

xiangling Wang, Dr.

Role: primary

xlwang71@163.com

8653182169841

Other Identifiers

KYLL-202304-31

Identifier Type: -

Identifier Source: org_study_id