Metastatic Colorectal Cancer (CRC)Phase 2NCT07621497
FOLFOX8 Versus mFOLFOX6 With Bevacizumab or Cetuximab for First-Line Unresectable Metastatic Colorectal Cancer (Phase II)
A Phase 2 study testing Oxaliplatin, 5-Fluorouracil and Levofolinic Acid For Injection in people with Metastatic Colorectal Cancer (CRC), run by Sun Yat-sen University at 3 sites in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer (CRC)
- What is being tested?
- Oxaliplatin, 5-Fluorouracil and Levofolinic Acid For Injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 229 participants
- Where
- 3 sitesChina
- Study dates
- 1 Nov 2026to 1 Jun 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510000
Feng Wang, MD, PhD, +86 020 87343795, wangfeng@sysucc.org.cn
wangzhq@sysucc.org.cn
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, 510120
Heping Li, +86 13710873975, liheping@mail.sysu.edu.cn
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, 201321
Wenhua Li, +86 18017317210, whliiris@hotmail.com
About this study
Official title: A Prospective, Multicenter, Randomized Controlled, Phase II Study to Evaluate the Efficacy and Safety of FOLFOX8 Versus mFOLFOX6 Combined With Bevacizumab or Cetuximab as First-Line Treatment for Unresectable Metastatic Colorectal Cancer
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.
Read the 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.
- Conditions
- Metastatic Colorectal Cancer (CRC)
- Being tested
- Oxaliplatin, 5-Fluorouracil, Levofolinic Acid For Injection, Calcium Folinate, Bevacizumab
- Keywords
- FOLFOX8, Levofolinic Acid For Injection, First-line treatment
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
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.
5-FluorouracilDrug
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.
Levofolinic Acid For InjectionDrug
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.
Calcium FolinateDrug
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.
BevacizumabDrug
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.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Calcium Folinate; Drug: Bevacizumab; Drug: Cetuximab (EGFR inhibitor) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival（PFS）
Defined as the time from randomization to disease progression or death from any cause.
Measured: From date of randomization to disease progression or death, an average of 14 months.
Secondary outcomes (4)
Objective Response Rate（ORR）
Defined as the proportion of subjects achieving complete response or partial response evaluated by investigator based on RECIST 1.1
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From first dose of study treatment to 28 days after last dose, an average of 15 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jun 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 Nov 2029 (estimated)
- Study completion1 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 229 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Feng Wang, Sun Yat-sen University
- Investigators
- Feng Wang, Principal investigator, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07621497
- Sponsor's protocol ID
- HL-ZY-054
- Status last verified
- Oct 2026
- First submitted
- 20 May 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No