First-line Treatment of MCapOX + Cetuximab Vs. MFOLFOX6 + Cetuximab for RAS/BRAF Wild-type, MSS, Unresectable Left-Sided MCRC: a Multicenter, Randomized, Controlled, Phase III Study

Phase 3

Not yet recruiting

• Conditions: Colorectal Cancer (CRC); Capecitabine; Cetuximab
• Interventions: Drug: mCapOX plus Cetuximab; Drug: mFOLFOX6 plus Cetuximab

• Registration Number: NCT06616259
• Lead Sponsor: Meng Qiu

Brief Summary

This multicenter, randomized, controlled, phase III study is conducted to evaluate the efficacy and safety of first line mCapOX plus Cetuximab versus mFOLFOX6 plus Cetuximab for RAS/BRAF wild-type, MSS, Unresectable Left-Sided mCRC.

Detailed Description

Study participants who meet the enrollment criteria will be randomly assigned in a 1:1 ratio to either the mCapOX + cetuximab or mFOLFOX6 + cetuximab treatment groups, and those who have achieved control of their disease (Complete response \[CR\] + Partial response \[PR\] + Stable disease \[SD\]) after a maximum of 12 cycles of first-line induction therapy in both groups will continue to receive Capecitabine or Capecitabine + Cetuximab maintenance therapy until disease progression or toxicity is not tolerated or informed consent is withdrawn.

Study Timeline

• Status Verified: 2024-09
• Study First Submitted: 2024-09-17
• Study First Submitted QC: 2024-09-24
• Last Update Submitted: 2024-09-24
• Study Start: 2024-09-26
• Study First Posted: 2024-09-27
• Last Update Posted: 2024-09-27
• Primary Completion: 2028-09-30
• Study Completion: 2029-09-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 452

Inclusion Criteria

• Able to provide written informed consent and can understand and comply with the requirements of the study.
• Men and women ≥ 18 years of age.
• Patients with histologically or cytologically confirmed RAS and BRAF wild-type, MSS/pMMR, metastatic left-sided colorectal adenocarcinoma.
• Presence of at least one evaluable lesion, as defined in RECIST Version 1.1.
• With an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• No palliative first-line chemotherapy, targeted, immunotherapy, or prior platinum-based adjuvant chemotherapy, relapse more than 12 months from the end of adjuvant chemotherapy.
• According to the imaging findings and surgical assessment of initial unresectable, synchronous metastatic colorectal cancer, no serious complications of the primary tumor (obstruction, perforation, massive hemorrhage that cannot be treated in internal medicine, etc.) .
• Requirements for lab indicators: neutrophils ≥ 1.5 × 10^9/L, platelets ≥ 75 × 10^9/L, hemoglobin ≥ 8 g/dL; total bilirubin ≤ 1.5 × upper limit of normal (UNL); ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 × UNL (≤ 5 × UNL if liver metastases); alkaline phosphatase ≤ 2.5 × UNL (≤ 5 × UNL if liver metastases, ≤ 10 × UNL if bone metastases); LDH < 1500 U/L; creatinine clearance (calculated according to Cockcroft and Gault formula) > 50 mL/min or serum creatinine ≤ 1.5 × UNL.

Exclusion Criteria

• Patients with mCRC who were initially resectable with R0 resection or radiofrequency or SBRT were excluded.
• Patients diagnosed with MSI-H or dMMR by PCR or immunohistochemistry
• Hypersensitivity to any therapeutic agent.
• Patients who received adjuvant chemotherapy containing oxaliplatin and fluorouracil within 12 months before entering the study.
• Patients who have failed one or more palliative chemotherapy regimens.
• Patients with uncontrolled hepatitis B virus.
• Peripheral neuropathy ≥ CTC grade 2.
• Neurological or psychiatric disorders affecting cognitive performance.
• Patients with central nervous system metastasis could not be controlled with radiotherapy.
• Previous enteritis, chronic diarrhea, or recurrent bowel obstruction; uncontrolled bleeding from internal medicine; bowel perforation.
• Uncontrolled concomitant diseases within 6 months before the study, including unstable angina, acute myocardial infarction, cerebrovascular accident, etc.
• Pregnant or lactating patients, or those of childbearing potential who do not take adequate contraceptive measures.
• History of other malignancies, but no disease-free survival longer than 5 years.
• Patients concurrently receiving other anti-tumor treatment or participating in other interventional clinical trials.
• Patients who are unable to comply with this study for psychological, family or social reasons.
• Patients with other serious diseases that the investigator considers not suitable.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	mCapOX plus Cetuximab	mCapOX (Capecitabine+Oxaliplatin) plus Cetuximab
Arm B	mFOLFOX6 plus Cetuximab	mFOLFOX6 (Fluorouracil+Leucovorin+Oxaliplatin) plus Cetuximab

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS)	up to 3 years	Progression free survival is defined as the period from randomization to disease progress or death. Includes first-line induction therapy and maintenance therapy.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR)	6 months	Defined as the proportion of participants acquired Complete response (CR) or Partial response (PR) during treatment. Based on RECIST 1.1.
Disease control rate (DCR)	6 months	Defined as the proportion of patients who acquired Complete response (CR), Partial response (PR), or Stable disease (SD) during treatment. Based on RECIST 1.1.
Time to Failure of Strategy (TFS)	up to 3 years	Defined as the time from the date of randomization to \[secondary disease progression after reintroduction of first-line induction chemotherapy following maintenance therapy disease progression\] or \[all-cause death\].; If participants progressed on maintenance therapy after first-line induction chemotherapy without reintroduction of first-line induction chemotherapy or progressed during first-line induction chemotherapy, TFS equals PFS
Overall Survival (OS)	up to 5 years	Defined as the period from randomization to death from any cause
Adverse Event rate	up to 3 years	The rate of adverse event after treatment
Pharmacoeconomic	up to 3 years	Including CERs (Cost-Effectiveness Ratios) and ICERs (Incremental Cost-Effectiveness Ratios).; CERs：Defined as the ratio of the total costs of a medical intervention to the health benefits gained from that intervention.; ICERs：Defined as the ratio of the difference in costs between two alternative interventions（Arm A and Arm B） to the difference in their effectiveness.
Quality of Life	up to 3 years	Assessment of quality of life through the Quality of Life Questionnaire (QLQ)

Trial Locations

Locations (1)

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