Colorectal CancerPhase 3NCT07362836
Fruquintinib Versus Bevacizumab Plus Chemotherapy in Second-Line RAS-Mutant Metastatic Colorectal Cancer (FRU-RAS)
A Phase 3 study testing fruquintinib+chemotherapy and bevacizumab+chemotherapy in people with Colorectal Cancer, run by Fudan University.
Trial summary
The goal of this clinical trial is to evaluate the efficacy and safety of fru+chemo as second-line therapy for patients with RAS-Mutant Metastatic Colorectal Cancer, especially when compared with the standard therapy BEV+chemo. The trial aims to provide this kind of patients with a more beneficial therapeutic option. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- fruquintinib+chemotherapy and bevacizumab+chemotherapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 224 participants
- Where
- No sites listed yet
- Study dates
- 31 Jan 2026to 30 Jan 2030
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients voluntarily participate in the study, sign the informed consent form, and have good compliance.
- 18 years ≤ age ≤ 75 years.
- Histologically and/or cytologically confirmed unresectable metastatic colorectal cancer.
- RAS mutant type.
- Previously received chemotherapy based on fluoropyrimidines (5-fluorouracil or capecitabine, etc.), oxaliplatin or irinotecan; previous adjuvant/neoadjuvant therapy is allowed. If recurrence or metastasis occurs during or within 6 months after adjuvant/neoadjuvant therapy, it is considered as the failure of first-line systemic chemotherapy for advanced disease.
- Patients must have at least one measurable lesion (RECIST 1.1).
Show all 10Show fewer
- ECOG performance status 0-1.
- Expected survival ≥ 12 weeks.
- Blood tests (without blood transfusion within 14 days) 1) Absolute neutrophil count ≥ 1.5×10^9/L, platelet count ≥ 100×10^9/L, hemoglobin concentration ≥ 9g/dL; 2) Liver function tests (AST and ALT ≤ 2.5×ULN, bilirubin ≤ 1.5×ULN; if there is liver metastasis, AST and ALT ≤ 5×ULN); 3) Renal function (serum creatinine (Cr) ≤ 1.5×ULN, or creatinine clearance rate (CCr) ≥ 60ml/min); 4) Coagulation, international normalized ratio (INR) ≤ 1.5×ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5×ULN; 5) Thyroid function, thyroid stimulating hormone (TSH) ≤ upper limit of normal (ULN); if abnormal, FT3 and FT4 levels should be examined, and patients with normal FT3 and FT4 levels can be included.
- Women of childbearing age are willing to use medically approved effective contraceptive measures (such as intrauterine devices, contraceptives or condoms) during the study and for 3 months after the last administration of the study drug; for male subjects whose partners are of childbearing age, it is recommended to take effective contraceptive measures during the study and for 3 months after the last administration of the study drug.
Who cannot join
- Enrolled in another clinical study within the 4 weeks prior to enrollment in this study;
- Previously received anti-angiogenic small molecule targeted drug treatment, such as fruquintinib, etc.;
- Symptomatic brain or leptomeningeal metastases (except for those who have undergone local radiotherapy or surgery for brain metastases for more than 6 months and have stable disease control);
- Experienced severe infection within 4 weeks prior to enrollment (e.g., requiring intravenous infusion of antibiotics, antifungal drugs, or antiviral drugs);
- Hypertension that cannot be well controlled with antihypertensive drugs (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
- Had active bleeding or coagulation disorders within 2 months prior to enrollment, had a bleeding tendency or was receiving thrombolytic therapy, and was assessed by the investigator as unsuitable for enrollment;
Show all 14Show fewer
- Had active heart disease within 6 months prior to treatment, including myocardial infarction, severe/unstable angina pectoris. Echocardiography showed left ventricular ejection fraction < 50%, or had poorly controlled arrhythmia;
- Had other malignant tumors within 5 years prior to enrollment or at the same time (except for cured basal cell carcinoma of the skin and cervical carcinoma in situ);
- Known to be allergic to the study drug or any of its excipients;
- Unable to take oral medication or the investigator judged that the subject had a condition that affected drug absorption;
- Pregnant (positive pregnancy test before medication) or breastfeeding women;
- Had active or uncontrolled severe infections 1) Known human immunodeficiency virus (HIV) infection; 2) Known history of clinically significant liver disease, including viral hepatitis [known hepatitis B virus (HBV) carriers must be excluded from active HBV infection, i.e., HBV DNA positive (>1×10^4 copies/mL or >2000 IU/mL); 3) Known hepatitis C virus (HCV) infection and HCV RNA positive (>1×10^3 copies/mL), or other hepatitis, liver cirrhosis;
- Urinalysis indicated proteinuria ≥ 2+, and 24-hour urine protein quantification > 1.0g;
- Other situations judged by the investigator as unsuitable for inclusion in this study.
About this study
Official title: Fruquintinib Versus Bevacizumab Plus Chemotherapy as Second-Line Therapy for Patients With RAS-Mutant Metastatic Colorectal Cancer (FRU-RAS): A Multicenter Randomized Controlled Trial
The goal of this clinical trial is to evaluate the efficacy and safety of fru+chemo as second-line therapy for patients with RAS-Mutant Metastatic Colorectal Cancer, especially when compared with the standard therapy BEV+chemo.
The trial aims to provide this kind of patients with a more beneficial therapeutic option.
Eligible patients were randomly assigned to the experimental group or the control group at a ratio of 1:1, Experimental group: Patients received fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), Control group: Patients received bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen),
Read the detailed description
Eligible patients were randomly assigned to the experimental group or the control group at a ratio of 1:1, stratified by bevacizumab treatment history (yes vs no), and metastatic sites (≤2 vs >2).
Experimental group: Patients received fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), with the choice of oxaliplatin-based or irinotecan-based chemotherapy regimen depending on the previous chemotherapy regimen (chemotherapy switch): fruquintinib: 4mg, qd po, d1-21, q4w; FOLFIRI regimen: irinotecan 180mg/m2 intravenous infusion for 30-90min on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. mFOLFOX6 regimen: oxaliplatin 85mg/m2 intravenous infusion for 2h on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle.
Control group: Patients received bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), with the choice of oxaliplatin-based or irinotecan-based chemotherapy regimen depending on the previous chemotherapy regimen (chemotherapy switch): bevacizumab: 5mg/kg, ivgtt, d1, 15, q4w; FOLFIRI regimen: irinotecan 180mg/m2 intravenous infusion for 30-90min on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. mFOLFOX6 regimen: oxaliplatin 85mg/m2 intravenous infusion for 2h on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle.
During the combination treatment period, the tumor response was evaluated by imaging every 8 weeks. After at least 6 cycles of continuous administration, the following evaluations were made: ① If the patient met the conditions for conversion therapy, radical local treatments such as surgical resection or radiofrequency ablation could be performed. Patients in the fruquintinib group needed to discontinue the drug for about 2 weeks before surgery, while those in the bevacizumab group needed to discontinue for about 6 weeks. ② Patients who achieved disease control entered the maintenance treatment stage and received fruquintinib combined with chemotherapy or bevacizumab combined with chemotherapy, with the chemotherapy regimen determined by the doctor. The treatment continued until disease progression, intolerable toxicity, or withdrawal of informed consent occurred. During the maintenance treatment period, the tumor response was evaluated by imaging every 8 weeks. Safety observation indicators included adverse events, changes in laboratory indicators, vital signs, and electrocardiogram changes. The subsequent tumor treatment and survival follow-up after progression were recorded.
- Conditions
- Colorectal Cancer
- Being tested
- fruquintinib+chemotherapy, bevacizumab+chemotherapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fruquintinib+chemotherapyDrug
fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)
bevacizumab+chemotherapyDrug
bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen)
| Study group | Role | What they receive |
|---|---|---|
| fruquintinib+chemotherapy | Experimental | fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen) Receives: Drug: fruquintinib+chemotherapy |
| bevacizumab+chemotherapy | Active comparator | bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen) Receives: Drug: bevacizumab+chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival
Progression-Free Survival (PFS) is a time-to-event outcome commonly used as a primary or secondary endpoint in oncology clinical trials. It quantifies the duration a patient lives without disease progression or death, providing an early indicator of treatment efficacy.
Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Secondary outcomes (3)
Objective Response Rate
ORR (Objective Response Rate) refers to the proportion of patients in a clinical trial whose tumor burden is reduced by a predefined amount, specifically achieving either a Complete Response (CR) or Partial Response (PR), as assessed by the investigator based on RECIST (Response Evaluation Criteria in Solid Tumors) criteria.
Measured: ORR will be assessed up to Week 24 after randomization
Disease Control Rate
Disease Control Rate (DCR) is defined as the percentage of patients whose disease responds to treatment (i.e., achieves Complete Response (CR) or Partial Response (PR)) or remains stable (Stable Disease, SD) over a defined period of time. It reflects the proportion of patients who experience tumor shrinkage or disease stabilization without progression.
Measured: DCR will be assessed up to Week 24 after randomization.
Overall Survival
Overall Survival (OS) is the most definitive and direct measure of clinical benefit in cancer trials. It is defined as the time from randomization (or start of treatment) to death from any cause. This endpoint captures the ultimate outcome of interest: whether a patient is alive.
Measured: From date of randomization until the date of death from any cause, assessed up to 60 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2026
- Study start31 Jan 2026 (estimated)
- Primary completion30 Dec 2028 (estimated)
- Study completion30 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Fudan 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 224 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fudan University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ye Xu, Fudan University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07362836
- Sponsor's protocol ID
- HMPL-013-FLAG-C140
- Status last verified
- Jan 2026
- First submitted
- 4 Jan 2026
- Last updated
- 23 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fruquintinib Versus Bevacizumab Plus Chemotherapy as Second-Line Therapy for Patients With RAS-Mutant Metastatic Colorectal Cancer (FRU-RAS): A Multicenter Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT07362836
- Acronym / sponsor ID
- HMPL-013-FLAG-C140
- Conditions
- Colorectal Cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 224 participants (estimated)
- Lead sponsor
- Fudan UniversityUniversity, hospital or other
- Study start
- 31 Jan 2026 (estimated)
- Primary completion
- 30 Dec 2028 (estimated)
- Study completion
- 30 Jan 2030 (estimated)
- First posted
- 23 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate the efficacy and safety of fru+chemo as second-line therapy for patients with RAS-Mutant Metastatic Colorectal Cancer, especially when compared with the standard therapy BEV+chemo.
The trial aims to provide this kind of patients with a more beneficial therapeutic option.
Eligible patients were randomly assigned to the experimental group or the control group at a ratio of 1:1, Experimental group: Patients received fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), Control group: Patients received bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen),
Detailed description
Eligible patients were randomly assigned to the experimental group or the control group at a ratio of 1:1, stratified by bevacizumab treatment history (yes vs no), and metastatic sites (≤2 vs >2).
Experimental group: Patients received fruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), with the choice of oxaliplatin-based or irinotecan-based chemotherapy regimen depending on the previous chemotherapy regimen (chemotherapy switch): fruquintinib: 4mg, qd po, d1-21, q4w; FOLFIRI regimen: irinotecan 180mg/m2 intravenous infusion for 30-90min on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. mFOLFOX6 regimen: oxaliplatin 85mg/m2 intravenous infusion for 2h on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle.
Control group: Patients received bevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen), with the choice of oxaliplatin-based or irinotecan-based chemotherapy regimen depending on the previous chemotherapy regimen (chemotherapy switch): bevacizumab: 5mg/kg, ivgtt, d1, 15, q4w; FOLFIRI regimen: irinotecan 180mg/m2 intravenous infusion for 30-90min on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle. mFOLFOX6 regimen: oxaliplatin 85mg/m2 intravenous infusion for 2h on days 1 and 15; LV 400mg/m2 intravenous infusion for 2h on days 1 and 15; 5-FU 400mg/m2 intravenous push on days 1 and 15, followed by 1200mg/(m2∙d) × 2d continuous intravenous infusion (total 2400mg/m2, infusion 46-48h); every 4 weeks as a treatment cycle.
During the combination treatment period, the tumor response was evaluated by imaging every 8 weeks. After at least 6 cycles of continuous administration, the following evaluations were made: ① If the patient met the conditions for conversion therapy, radical local treatments such as surgical resection or radiofrequency ablation could be performed. Patients in the fruquintinib group needed to discontinue the drug for about 2 weeks before surgery, while those in the bevacizumab group needed to discontinue for about 6 weeks. ② Patients who achieved disease control entered the maintenance treatment stage and received fruquintinib combined with chemotherapy or bevacizumab combined with chemotherapy, with the chemotherapy regimen determined by the doctor. The treatment continued until disease progression, intolerable toxicity, or withdrawal of informed consent occurred. During the maintenance treatment period, the tumor response was evaluated by imaging every 8 weeks. Safety observation indicators included adverse events, changes in laboratory indicators, vital signs, and electrocardiogram changes. The subsequent tumor treatment and survival follow-up after progression were recorded.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| fruquintinib+chemotherapy | Experimental | Drug: fruquintinib+chemotherapyfruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen) |
| bevacizumab+chemotherapy | Active comparator | Drug: bevacizumab+chemotherapybevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients voluntarily participate in the study, sign the informed consent form, and have good compliance.
- 18 years ≤ age ≤ 75 years.
- Histologically and/or cytologically confirmed unresectable metastatic colorectal cancer.
- RAS mutant type.
- Previously received chemotherapy based on fluoropyrimidines (5-fluorouracil or capecitabine, etc.), oxaliplatin or irinotecan; previous adjuvant/neoadjuvant therapy is allowed. If recurrence or metastasis occurs during or within 6 months after adjuvant/neoadjuvant therapy, it is considered as the failure of first-line systemic chemotherapy for advanced disease.
Key exclusion criteria (14 listed)
- Enrolled in another clinical study within the 4 weeks prior to enrollment in this study;
- Previously received anti-angiogenic small molecule targeted drug treatment, such as fruquintinib, etc.;
- Symptomatic brain or leptomeningeal metastases (except for those who have undergone local radiotherapy or surgery for brain metastases for more than 6 months and have stable disease control);
- Experienced severe infection within 4 weeks prior to enrollment (e.g., requiring intravenous infusion of antibiotics, antifungal drugs, or antiviral drugs);
- Hypertension that cannot be well controlled with antihypertensive drugs (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fruquintinib+chemotherapyfruquintinib combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen) | Drug | fruquintinib+chemotherapy |
| bevacizumab+chemotherapybevacizumab combined with chemotherapy (mFOLFOX6 or FOLFIRI regimen) | Drug | bevacizumab+chemotherapy |
Primary outcome
Progression-Free Survival
Time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months
Progression-Free Survival (PFS) is a time-to-event outcome commonly used as a primary or secondary endpoint in oncology clinical trials. It quantifies the duration a patient lives without disease progression or death, providing an early indicator of treatment efficacy.
3 secondary outcomes
Objective Response Rate
Time frame: ORR will be assessed up to Week 24 after randomization
Disease Control Rate
Time frame: DCR will be assessed up to Week 24 after randomization.
Overall Survival
Time frame: From date of randomization until the date of death from any cause, assessed up to 60 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2026.
Related trials for Colorectal Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Active, not recruiting
Streamlined Geriatric and Oncological Evaluation Based On IC Technology
Breast Cancer, Comorbidities and Coexisting Conditions
RecruitingObservational study
Pre- and On-treatment Multi-omics Profiling of Locally Advanced Rectal Cancer
Rectal Neoplasms
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 2
Tislelizumab in People With Colorectal Cancer
Colorectal Cancer
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fruquintinib+chemotherapy and bevacizumab+chemotherapy in people with Colorectal Cancer, run by Fudan University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (time frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2026.