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

Official title

First-line Treatment of MCapOX in Combination with Cetuximab Versus MFOLFOX6 in Combination with Cetuximab for RAS/BRAF Wild-type, MSS, Unresectable Left-Sided Metastatic Colorectal Cancer: a Multicenter, Randomized, Controlled, Phase III Study

Overview

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+ Cetuximab maintenance therapy until disease progression or toxicity is not tolerated or informed consent is withdrawn.

Interventions

• Drug mCapOX plus Cetuximab
  mCapOX plus Cetuximab Induction therapy：Capecitabine 1000mg/m2 po, bid, D1-7 + Oxaliplatin ivgtt 85mg/m2, D1 + Cetuximab ivgtt 500mg/m2, D1; Q2W. Up to 12 cycle, if no progression, enter maintenance therapy. Maintenance therapy: Capecitabine 1000mg/m2 po, bid, D1-7 + Cetuximab ivgtt 500mg/m2, D1; Q2W. Until disease progression or toxicity is not tolerated. Cetuximab can be discontinued alone if not tolerated. Treatment after progression of maintenance therapy: Participants have the option to a
• Drug mFOLFOX6 plus Cetuximab
  mFOLFOX6 plus Cetuximab Induction therapy：Oxaliplatin ivgtt 85mg/m2, D1 + Leucovorin ivgtt 400mg/m2, D1 + Fluorouracil iv bolus 400mg/m2, D1 + Fluorouracil 2400mg/m2 continuous infusion for 46-48h + Cetuximab ivgtt 500mg/m2, D1; Q2W. Up to 12 cycle, if no progression, enter maintenance therapy. Maintenance therapy: Capecitabine 1000mg/m2 po, bid, D1-7 + Cetuximab ivgtt 500mg/m2, D1; Q2W. Until disease progression or toxicity is not tolerated. Cetuximab can be discontinued alone if not tolerated

Primary outcome measures

• Progression free survival (PFS) [Time frame: up to 3 years]

Secondary outcome measures (7)

• Objective Response Rate (ORR) [Time frame: 6 months]
• Disease control rate (DCR) [Time frame: 6 months]
• Time to Failure of Strategy (TFS) [Time frame: up to 3 years]
• Overall Survival (OS) [Time frame: up to 5 years]
• Adverse Event rate [Time frame: up to 3 years]
• Pharmacoeconomic [Time frame: up to 3 years]
• Quality of Life [Time frame: up to 3 years]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• West China Hospital Sichuan University — Chengdu

Identifiers

NCT: NCT06616259 · 20240716

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗