Metastatic Colorectal Cancer (CRC)
Conditions
Keywords
FOLFOX8, Levofolinic Acid For Injection, First-line treatment
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.
Detailed description
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.
Interventions
DRUGOxaliplatin
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.
DRUG5-Fluorouracil
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.
DRUGLevofolinic Acid For Injection
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.
DRUGCalcium Folinate
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.
DRUGBevacizumab
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.
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years, male or female. 2. ECOG performance status 0-2. 3. Histologically or cytologically confirmed unresectable metastatic colorectal cancer with no prior treatment for unresectable or metastatic disease. 4. 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. 5. Expected survival \> 3 months.
Exclusion criteria
1. Known allergy to the study drug(s) and/or their excipients. 2. Contraindications to chemotherapy. 3. Patients with MSI-H or dMMR colorectal cancer. 4. Patients with BRAF mutation. 5. Pregnant or breastfeeding women. 6. 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. 7. Patients with systemic medical or psychiatric disorders that make them unsuitable for chemotherapy. 8. Patients deemed unsuitable for enrollment in this study by the investigator's judgment. 9. Participation in another clinical trial of an investigational drug within 4 weeks prior to randomization.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival（PFS） | From date of randomization to disease progression or death, an average of 14 months. | Defined as the time from randomization to disease progression or death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate（ORR） | From randomization until disease progression or death, an average of 14 months. | Defined as the proportion of subjects achieving complete response or partial response evaluated by investigator based on RECIST 1.1 |
| Overall Survival (OS) | From randomization until death, an average of 30 months. | Defined as the time from randomization to death from any cause. |
| Impact of Treatment Regimen on Infusion Time | Measured from cycle 1 until treatment discontinuation，an average of 14 months | Total time required for intravenous infusion of leucovorin/Levofolinic Acid For Injection and 5-FU per cycle. |
| Incidence of Adverse Events（AEs） | From first dose of study treatment to 28 days after last dose, an average of 15 months. | The incidence, severity, and causality of treatment-emergent adverse events (TEAEs) will be assessed according to CTCAE v5.0. |
Countries
China
Contacts
CONTACTFeng Wang
PRINCIPAL_INVESTIGATORFeng Wang
Sun Yat-Sen University Cancer Center
Outcome results
None listed