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

NCT06616259 | Not Yet Recruiting Phase 3

• 1 other identifier: 20240716
• Study Type: interventional
• Target: 452
• Locations: 1 country
• Sites: 1

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.

Conditions

Colorectal Cancer (CRC); Capecitabine; Cetuximab

Keywords

CAPCET-III

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Objective Response Rate (ORR)

  6 months

• Disease control rate (DCR)

  6 months

• Time to Failure of Strategy (TFS)

  up to 3 years

• Overall Survival (OS)

  up to 5 years

• Adverse Event rate

  up to 3 years

Study Arms (2)

Arm A

EXPERIMENTAL

mCapOX (Capecitabine+Oxaliplatin) plus Cetuximab

Drug: mCapOX plus Cetuximab

Arm B

ACTIVE COMPARATOR

mFOLFOX6 (Fluorouracil+Leucovorin+Oxaliplatin) plus Cetuximab

Drug: mFOLFOX6 plus Cetuximab

Interventions

mCapOX plus Cetuximab DRUG

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.

Arm A

mFOLFOX6 plus Cetuximab DRUG

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.

Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Meng Qiu: lead

Study Sites (1)

West China Hospital Sichuan University

Chengdu, Sichuan, 610041, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Cetuximab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Yuwen Zhou, M.D.

CONTACT

+86 15328007741; drzhouyuwen@163.com

Meng Qiu, M.D.

CONTACT

qiumeng@wchscu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: September 27, 2024
• Study Start: September 26, 2024
• Primary Completion (Estimated): September 30, 2028
• Study Completion (Estimated): September 30, 2029
• Last Updated: September 27, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)