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 (CAPCET-III)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Capecitabine; Colorectal Cancer (CRC); Cetuximab
• Intervention / Treatment: Drug: mCapOX plus Cetuximab; Drug: mFOLFOX6 plus Cetuximab

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+ Cetuximab maintenance therapy until disease progression or toxicity is not tolerated or informed consent is withdrawn.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 Type: Interventional
• Enrollment (Estimated): 452
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Yuwen Zhou, M.D.; Phone Number: +86 15328007741; Email: drzhouyuwen@163.com
• Study Contact Backup: Name: Meng Qiu, M.D.; Email: qiumeng@wchscu.cn

Study Locations

• China
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan University
      • Contact: Yuwen Zhou, M.D.; Phone Number: +028 15328007741; Email: drzhouyuwen@163.com
      • Contact: Meng Qiu, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; mCapOX (Capecitabine+Oxaliplatin) plus Cetuximab	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 accept reintroducing the first-line induction chemotherapy regimen (mCapOx or mFOLFOX6 in combination with cetuximab) or accept second-line therapy.
Active Comparator: Arm B; mFOLFOX6 (Fluorouracil+Leucovorin+Oxaliplatin) plus Cetuximab	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. Treatment after progression of maintenance therapy: Participants have the option to accept reintroducing the first-line induction chemotherapy regimen (mCapOx or mFOLFOX6 in combination with cetuximab) or accept second-line therapy.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	Defined as the proportion of participants acquired Complete response (CR) or Partial response (PR) during treatment. Based on RECIST 1.1.	6 months
Disease control rate (DCR)	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.	6 months
Time to Failure of Strategy (TFS)	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	up to 3 years
Overall Survival (OS)	Defined as the period from randomization to death from any cause	up to 5 years
Adverse Event rate	The rate of adverse event after treatment	up to 3 years
Pharmacoeconomic	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.	up to 3 years
Quality of Life	Assessment of quality of life through the Quality of Life Questionnaire (QLQ)	up to 3 years

Collaborators and Investigators

• Sponsor: Meng Qiu

Study record dates

Study Major Dates

• Study Start (Estimated): September 26, 2024
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: September 17, 2024
• First Submitted That Met QC Criteria: September 24, 2024
• First Posted (Actual): September 27, 2024

Study Record Updates

• Last Update Posted (Actual): September 27, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: CAPCET-III
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: 20240716

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No