FOLFOX8 Versus mFOLFOX6 With Bevacizumab or Cetuximab for First-Line Unresectable Metastatic Colorectal Cancer (Phase II)

NCT07621497 | Not Yet Recruiting Phase 2

• 1 other identifier: HL-ZY-054
• Study Type: interventional
• Target: 229
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, multicenter, randomized controlled, phase II study. It is expected to enroll 229 patients and aims to evaluate the efficacy and safety of FOLFOX8 versus mFOLFOX6 combined with bevacizumab or cetuximab as first-line treatment for unresectable metastatic colorectal cancer. The primary objective is to assess progression-free survival (PFS) of the patients. Secondary objectives include assessment of objective response rate (ORR), overall survival (OS), safety, and other outcomes.

Conditions

Metastatic Colorectal Cancer (CRC)

Keywords

FOLFOX8; Levofolinic Acid For Injection; First-line treatment

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival（PFS）

  Defined as the time from randomization to disease progression or death from any cause.

  From date of randomization to disease progression or death, an average of 14 months.

Secondary Outcomes (4)

• Objective Response Rate（ORR）

  From randomization until disease progression or death, an average of 14 months.

• Overall Survival (OS)

  From randomization until death, an average of 30 months.

• Impact of Treatment Regimen on Infusion Time

  Measured from cycle 1 until treatment discontinuation，an average of 14 months

• Incidence of Adverse Events（AEs）

  From first dose of study treatment to 28 days after last dose, an average of 15 months.

Study Arms (2)

FOLFOX8

EXPERIMENTAL

Patients receive oxaliplatin, 5-FU bolus, and a concurrent infusion of Levofolinic Acid For Injection mixed with 5-FU, repeated every 2 weeks for up to 12 cycles. From cycle 2 onward, bevacizumab or cetuximab is added based on RAS mutation status and tumor location. After 12 cycles, patients without disease progression enter maintenance therapy with concurrent infusion of Levofolinic Acid For Injection mixed with 5-FU (without oxaliplatin) plus continued targeted therapy , repeated every 2 weeks until disease progression or unacceptable toxicity.

Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Levofolinic Acid For Injection; Drug: Bevacizumab; Drug: Cetuximab (EGFR inhibitor)

mFOLFOX6

ACTIVE COMPARATOR

Patients receive oxaliplatin, calcium folinate, 5-FU bolus, and 5-FU continuous infusion, repeated every 2 weeks for up to 12 cycles. From cycle 2 onward, bevacizumab or cetuximab is added based on RAS mutation status and tumor location. After 12 cycles, patients without disease progression enter maintenance therapy with calcium folinate, 5-FU bolus, and 5-FU continuous infusion (without oxaliplatin) plus continued targeted therapy , repeated every 2 weeks until disease progression or unacceptable toxicity.

Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Calcium Folinate; Drug: Bevacizumab; Drug: Cetuximab (EGFR inhibitor)

Interventions

Oxaliplatin DRUG

85 mg/m² intravenously over 2 hours on Day 1, every 2 weeks for up to 12 cycles. For patients without disease progression after 12 cycles, oxaliplatin is discontinued and not used in maintenance.

FOLFOX8; mFOLFOX6

5-Fluorouracil DRUG

400 mg/m² intravenous bolus on Day 1, followed by 2400 mg/m² administered as a continuous intravenous infusion over 46-48 hours. Cycle repeats every 2 weeks for up to 12 cycles. Patients without disease progression then enter maintenance with the same 5-FU regimen every 2 weeks until disease progression or unacceptable toxicity.

FOLFOX8; mFOLFOX6

Levofolinic Acid For Injection DRUG

200 mg/m² mixed with 5-FU 2400 mg/m² as a continuous intravenous infusion over 46-48 hours on Day 1 (concurrent infusion). Cycle repeats every 2 weeks for up to 12 cycles. Patients without disease progression then enter maintenance with the same mixture every 2 weeks until disease progression or unacceptable toxicity.

FOLFOX8

Calcium Folinate DRUG

400 mg/m² intravenously over 2 hours on Day 1, administered sequentially before 5-FU. Cycle repeats every 2 weeks for up to 12 cycles. Patients without disease progression then enter maintenance with the same dose and schedule of calcium folinate (without oxaliplatin) every 2 weeks until disease progression or unacceptable toxicity.

mFOLFOX6

Bevacizumab DRUG

5 mg/kg intravenously on Day 1 every 2 weeks, starting from Cycle 2 (after genetic testing results are available). Continue through induction and maintenance until disease progression or unacceptable toxicity.

FOLFOX8; mFOLFOX6

Cetuximab (EGFR inhibitor) DRUG

500 mg/m² intravenously over more than 2 hours on Day 1 every 2 weeks, starting from Cycle 2 (after genetic testing results are available). Continue through induction and maintenance until disease progression or unacceptable toxicity.

FOLFOX8; mFOLFOX6

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years, male or female.
• ECOG performance status 0-2.
• Histologically or cytologically confirmed unresectable metastatic colorectal cancer with no prior treatment for unresectable or metastatic disease.
• Adequate organ function: Hb ≥ 70 g/L; WBC ≥ 3.0×10⁹/L; NEUT ≥ 1.5×10⁹/L; PLT ≥ 75×10⁹/L; AST and ALT ≤ 3× ULN; sCr ≤ 2× ULN; TBIL ≤ 2× ULN.
• Expected survival \> 3 months.

You may not qualify if:

• Known allergy to the study drug(s) and/or their excipients.
• Contraindications to chemotherapy.
• Patients with MSI-H or dMMR colorectal cancer.
• Patients with BRAF mutation.
• Pregnant or breastfeeding women.
• History of any second malignancy within 2 years prior to randomization, except for cured localized tumors such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, cervical carcinoma in situ, or breast carcinoma in situ, which are allowed for enrollment.
• Patients with systemic medical or psychiatric disorders that make them unsuitable for chemotherapy.
• Patients deemed unsuitable for enrollment in this study by the investigator's judgment.
• Participation in another clinical trial of an investigational drug within 4 weeks prior to randomization.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Fluorouracil; Leucovorin; Injections; Bevacizumab; 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)

Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Drug Administration Routes; Drug Therapy; Therapeutics; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Feng Wang

  Sun Yat-Sen University Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Feng Wang

CONTACT

+86 020 87343795; wangfeng@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician, Department Director

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: June 2, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): June 1, 2030
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)