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.
Levofolinic Acid For Injection is the first approved class 2.1 sodium levoleucovorin formulation in China. It contains only the active l-isomer of levoleucovorin, with an equivalent dose half that of leucovorin. As a sodium salt, it has higher solubility, is compatible with 5-FU, and allows concurrent infusion. The FOLFOX8 regimen is based on mFOLFOX6 and takes advantage of the sodium salt formulation of Levofolinic Acid For Injection by changing the traditional sequential infusion of 5-FU and calcium levoleucovorin to concurrent infusion of Levofolinic Acid For Injection and 5-FU, thereby prolonging the duration of synergistic action and enhancing overall efficacy. It is expected to further delay disease progression in patients with colorectal cancer. This study is a prospective, multicenter, randomized controlled phase II trial. A total of 229 patients will be enrolled and randomly assigned to the experimental group (FOLFOX8) or the control group (mFOLFOX6). Targeted therapy (bevacizumab or cetuximab) will be selected based on the patient's RAS mutation status and tumor location. Treatment will be administered every two weeks. Before and after each treatment cycle, patients will undergo routine clinical examinations including blood tests. A maximum of 12 cycles will be given, and patients without disease progression will enter the maintenance phase. Tumor assessments will be performed every 8 weeks after the start of treatment (based on RECIST V1.1 criteria), and concomitant medications and adverse events will be recorded. The primary endpoint of this study is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), overall survival (OS), safety, and the impact of the treatment regimen on infusion time.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
229
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.
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.
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.
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.
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.
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.
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
Progression-Free Survival（PFS）
Defined as the time from randomization to disease progression or death from any cause.
Time frame: From date of randomization to disease progression or death, an average of 14 months.
Objective Response Rate（ORR）
Defined as the proportion of subjects achieving complete response or partial response evaluated by investigator based on RECIST 1.1
Time frame: From randomization until disease progression or death, an average of 14 months.
Overall Survival (OS)
Defined as the time from randomization to death from any cause.
Time frame: From randomization until death, an average of 30 months.
Impact of Treatment Regimen on Infusion Time
Total time required for intravenous infusion of leucovorin/Levofolinic Acid For Injection and 5-FU per cycle.
Time frame: Measured from cycle 1 until treatment discontinuation，an average of 14 months
Incidence of Adverse Events（AEs）
The incidence, severity, and causality of treatment-emergent adverse events (TEAEs) will be assessed according to CTCAE v5.0.
Time frame: From first dose of study treatment to 28 days after last dose, an average of 15 months.
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