Metastatic Colorectal Cancer (CRC)Phase 2NCT07286695
Fruquintinib Combined With Trifluridine/Tipiracil Versus Bevacizumab Combined With Trifluridine/Tipiracil for Advanced Metastatic Colorectal Cancer
A Phase 2 study testing Fruquintinib Combined With trifluridine/tipiracil and Bevacizumab combined with trifluridine/tipiracil in people with Metastatic Colorectal Cancer (CRC) and Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
Trial summary
Fruquintinib, as a standard treatment for refractory metastatic colorectal cancer (mCRC), has attracted increasing research efforts to explore its innovative strategies in combination with chemotherapy. Trifluridine/tipiracil plus bevacizumab is also a standard treatment for mCRC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Colorectal Cancer (CRC), Colorectal Cancer
- What is being tested?
- Fruquintinib Combined With trifluridine/tipiracil and Bevacizumab combined with trifluridine/tipiracil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 292 participants
- Where
- 1 siteChina
- Study dates
- 31 Dec 2025to 31 Dec 2029
- Phase
- Phase 2
- 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
- Have a full understanding of this study and voluntarily sign the informed consent form;
- Aged 18-75 years old (including 18 and 75 years old);
- Diagnosed with advanced metastatic colorectal adenocarcinoma by histopathological examination;
- Patients who have previously received first-line oxaliplatin and irinotecan treatment, or have received and failed at least two lines of standard chemotherapy regimens. These standard treatment regimens must include fluoropyrimidine-based drugs, oxaliplatin and irinotecan (with or without bevacizumab or cetuximab). Treatment failure is defined as disease progression occurring during treatment or within 3 months after the last treatment, or intolerable toxic side effects. Each line of treatment must include one or more chemotherapy drugs administered for ≥1 cycle; if recurrence or metastasis occurs during adjuvant/neoadjuvant treatment or within 6 months after completion of adjuvant/neoadjuvant treatment, the adjuvant/neoadjuvant treatment is considered a failure of first-line chemotherapy for advanced disease;
- Have previously received bevacizumab treatment;
- Must have at least one clear measurable lesion that meets the requirements of the Response Evaluation Criteria in Solid Tumors (RECIST 1.1);
Show all 11Show fewer
- ECOG performance status of 0-1;
- Expected survival time ≥12 weeks;
- Within 7 days before enrollment, the function of important organs must meet the following requirements (the use of any blood components and cell growth factors within 14 days before enrollment is not allowed):
- Absolute neutrophil count ≥1.5×10⁹/L; Platelets ≥80×10⁹/L; Hemoglobin ≥8g/dL; Total bilirubin ≤1.5×ULN (upper limit of normal); ALT (alanine aminotransferase) and AST (aspartate aminotransferase) ≤2.5×ULN (for patients with liver metastasis, ≤5×ULN); Serum creatinine ≤1.5×ULN, and estimated glomerular filtration rate ≥50ml/min; International Normalized Ratio (INR) ≤1.5 or activated partial thromboplastin time (APTT) ≤1.5×ULN;
- Good compliance and willingness to cooperate with follow-up.
Who cannot join
- Unable to comply with the study protocol or procedures;
- Previous treatment with TAS-102 or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) (e.g., anlotinib, apatinib, etc.);
- Participation in other drug clinical trials within 4 weeks before enrollment;
- Have received or is currently receiving other systemic anti-tumor treatments within 4 weeks prior to enrollment;
- Patients with currently uncontrolled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg) despite medication;
- Patients with current diseases or conditions that affect drug absorption, or patients unable to take oral medications;
Show all 15Show fewer
- Patients with active gastrointestinal diseases such as active gastric and duodenal ulcers, ulcerative colitis, active bleeding from unresected tumors, or other conditions judged by the investigator to potentially cause gastrointestinal bleeding or perforation;
- History of arterial thrombosis or deep vein thrombosis within 6 months before enrollment;
- Patients with evidence or medical history of significant bleeding tendency within 2 months before enrollment, such as melena, hematemesis, hemoptysis, fecal occult blood test (FOBT) result of ++ or above (for patients with FOBT result of + and existing primary lesions, gastroscopy must be performed to rule out bleeding or ulcers before enrollment);
- History of stroke and/or transient ischemic attack within 12 months before enrollment; presence of cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting within 6 months before enrollment; congestive heart failure of New York Heart Association (NYHA) class >2; ventricular arrhythmias requiring medication; left ventricular ejection fraction (LVEF) <50% (confirmed by echocardiography);
- History of other malignant tumors within the past 5 years, except for fully treated basal cell carcinoma or squamous cell carcinoma of the skin, carcinoma in situ of organs such as the cervix, early non-invasive lung cancer, and non-muscle-invasive bladder cancer;
- Clinically uncontrolled active infections, such as acute pneumonia, active hepatitis B or C (for patients with a history of hepatitis B virus infection, regardless of medication control, hepatitis B virus DNA ≥1×10⁴ copies/mL or >2000 IU/mL);
- Pregnant women (positive pregnancy test before medication administration) or lactating women;
- Urinalysis showing urine protein ≥2+, or 24-hour urine protein quantitation >1.0g;
- Patients deemed unsuitable for enrollment in this study by the investigator.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Cancer Hospital Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, 100000
Aiping Zhou, zhouap1825@126.com
About this study
Official title: A Multicenter, Open-label, Randomized Controlled Study of Fruquintinib Combined With Trifluridine/Tipiracil Versus Bevacizumab Combined With Trifluridine/Tipiracil in the Treatment of Patients With Advanced Metastatic Colorectal Cancer Who Failed Standard Chemotherapy
Fruquintinib, as a standard treatment for refractory metastatic colorectal cancer (mCRC), has attracted increasing research efforts to explore its innovative strategies in combination with chemotherapy. Trifluridine/tipiracil plus bevacizumab is also a standard treatment for mCRC. This study aims to explore the efficacy and safety of fruquintinib combined with trifluridine/tipiracil versus bevacizumab combined with trifluridine/tipiracil in the treatment of patients with advanced metastatic colorectal cancer who failed standard chemotherapy.
Read the detailed description
Phase II study comprises a safety run-in stage, and a randomized treatment stage.
Phase II (safety run-in stage): It aims to evaluate the safety and tolerability of combination therapy-comprising trifluridine/tipiracil and fruquintinib. Trifluridine/tipiracil was administered at a descending dose level starting from 35 mg/m² each time alongside fixed dose of fruquintinib in mCRC patients who have previously received first-line oxaliplatin and irinotecan-based therapy, or have failed at least two lines of standard chemotherapy regimens.
Phase II (randomized treatment stage): Upon determination of the recommend dose of trifluridine/tipiracil based on prior data, a randomized controlled study will be conducted in mCRC patients who have previously received first-line oxaliplatin and irinotecan-based therapy, or have failed at least two lines of standard chemotherapy regimens. Patients will be randomly assigned to two arms: experimental arm: Fruquintinib and trifluridine/tipiracil; active comparator arm: Bevacizumab and trifluridine/tipiracil.
- Being tested
- Fruquintinib Combined With trifluridine/tipiracil, Bevacizumab combined with trifluridine/tipiracil
- 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 Combined With trifluridine/tipiracilDrug
Experimental arm: Fruquintinib: 4mg once daily for 21 days on/7 days off, every 28 days; Trifluridine/tipiracil: taken at a recommended dose (based on the results of the safety run-in phase) each time orally twice a day on days 1-5 and 8-12, every 28 days.
Bevacizumab combined with trifluridine/tipiracilDrug
Active Comparator: Bevacizumab: 5 mg /kg, intravenously on days 1,15, every 28 days; Trifluridine/tipiracil: 35 mg/m²orally twice a day on days 1-5 and 8-12, every 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Fruquintinib and trifluridine/tipiracil | Experimental | Not described Receives: Drug: Fruquintinib Combined With trifluridine/tipiracil |
| Bevacizumab and trifluridine/tipiracil | Active comparator | Not described Receives: Drug: Bevacizumab combined with trifluridine/tipiracil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
Measured: About 3 years
Secondary outcomes (4)
Objective response rate (ORR)
ORR was defined as the percentage of patients with a best overall response of complete response (CR) or partial response (PR) per RECISTv1.1.
Measured: About 3 years
Disease control rate (DCR)
DCR was defined as the percentage of patients with a best overall response of confirmed complete or partial response, or stable disease (CR+ PR + SD) per RECISTv1.1.
Measured: About 3 years
Overall survival (OS)
OS was defined as the time from the date of randomization to the date of death due to any cause.
Measured: About 3 years
Adverse Events (AE)
Adverse Events (AE) as assessed by CTCAE v5.0, including serious adverse events (SAEs)
Measured: About 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2025
- Study start31 Dec 2025 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- More trials run by Cancer Institute and Hospital, Chinese Academy of Medical SciencesThe 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
- 292 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, AIPING ZHOU, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- Investigators
- Aiping Zhou, Principal investigator, Cancer Institute and Hospital, Chinese Academy of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07286695
- Sponsor's protocol ID
- HMPL-013-FLAG-C138
- Status last verified
- Jan 2026
- First submitted
- 3 Dec 2025
- Last updated
- 21 Jan 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD shared with other researchers will include the study protocol.
Publications
Nukatsuka M, Fujioka A, Nagase H, Tanaka G, Hayashi H. Evaluation of a Novel Combination Therapy, Based on Trifluridine/Tipiracil and Fruquintinib, against Colorectal Cancer. Chemotherapy. 2023;68(2):102-110. doi: 10.1159/000528867. Epub 2023 Jan 9.
PubMed 36623495Zou J, Wang Y, Xu J, Li J, Wang T, Zhang Y, Bai Y. A Retrospective Study of Trifluridine/Tipiracil with Fruquintinib in Patients with Chemorefractory Metastatic Colorectal Cancer. J Clin Med. 2023 Dec 21;13(1):57. doi: 10.3390/jcm13010057.
PubMed 38202064
Study at a glance
From the registry record, last updated by the sponsor on 21 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-label, Randomized Controlled Study of Fruquintinib Combined With Trifluridine/Tipiracil Versus Bevacizumab Combined With Trifluridine/Tipiracil in the Treatment of Patients With Advanced Metastatic Colorectal Cancer Who Failed Standard Chemotherapy
- ClinicalTrials.gov ID
- NCT07286695
- Acronym / sponsor ID
- HMPL-013-FLAG-C138
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 292 participants (estimated)
- Lead sponsor
- Cancer Institute and Hospital, Chinese Academy of Medical SciencesUniversity, hospital or other
- Study start
- 31 Dec 2025 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2029 (estimated)
- First posted
- 16 Dec 2025 (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.
Fruquintinib, as a standard treatment for refractory metastatic colorectal cancer (mCRC), has attracted increasing research efforts to explore its innovative strategies in combination with chemotherapy. Trifluridine/tipiracil plus bevacizumab is also a standard treatment for mCRC. This study aims to explore the efficacy and safety of fruquintinib combined with trifluridine/tipiracil versus bevacizumab combined with trifluridine/tipiracil in the treatment of patients with advanced metastatic colorectal cancer who failed standard chemotherapy.
Detailed description
Phase II study comprises a safety run-in stage, and a randomized treatment stage.
Phase II (safety run-in stage): It aims to evaluate the safety and tolerability of combination therapy-comprising trifluridine/tipiracil and fruquintinib. Trifluridine/tipiracil was administered at a descending dose level starting from 35 mg/m² each time alongside fixed dose of fruquintinib in mCRC patients who have previously received first-line oxaliplatin and irinotecan-based therapy, or have failed at least two lines of standard chemotherapy regimens.
Phase II (randomized treatment stage): Upon determination of the recommend dose of trifluridine/tipiracil based on prior data, a randomized controlled study will be conducted in mCRC patients who have previously received first-line oxaliplatin and irinotecan-based therapy, or have failed at least two lines of standard chemotherapy regimens. Patients will be randomly assigned to two arms: experimental arm: Fruquintinib and trifluridine/tipiracil; active comparator arm: Bevacizumab and trifluridine/tipiracil.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fruquintinib and trifluridine/tipiracil | Experimental | Drug: Fruquintinib Combined With trifluridine/tipiracil |
| Bevacizumab and trifluridine/tipiracil | Active comparator | Drug: Bevacizumab combined with trifluridine/tipiracil |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Have a full understanding of this study and voluntarily sign the informed consent form;
- Aged 18-75 years old (including 18 and 75 years old);
- Diagnosed with advanced metastatic colorectal adenocarcinoma by histopathological examination;
- Patients who have previously received first-line oxaliplatin and irinotecan treatment, or have received and failed at least two lines of standard chemotherapy regimens. These standard treatment regimens must include fluoropyrimidine-based drugs, oxaliplatin and irinotecan (with or without bevacizumab or cetuximab). Treatment failure is defined as disease progression occurring during treatment or within 3 months after the last treatment, or intolerable toxic side effects. Each line of treatment must include one or more chemotherapy drugs administered for ≥1 cycle; if recurrence or metastasis occurs during adjuvant/neoadjuvant treatment or within 6 months after completion of adjuvant/neoadjuvant treatment, the adjuvant/neoadjuvant treatment is considered a failure of first-line chemotherapy for advanced disease;
- Have previously received bevacizumab treatment;
Key exclusion criteria (15 listed)
- Unable to comply with the study protocol or procedures;
- Previous treatment with TAS-102 or vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) (e.g., anlotinib, apatinib, etc.);
- Participation in other drug clinical trials within 4 weeks before enrollment;
- Have received or is currently receiving other systemic anti-tumor treatments within 4 weeks prior to enrollment;
- Patients with currently uncontrolled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg) despite medication;
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 Combined With trifluridine/tipiracilExperimental arm: Fruquintinib: 4mg once daily for 21 days on/7 days off, every 28 days; Trifluridine/tipiracil: taken at a recommended dose (based on the results of the safety run-in phase) each time orally twice a day on days 1-5 and 8-12, every 28 days. | Drug | Fruquintinib and trifluridine/tipiracil |
| Bevacizumab combined with trifluridine/tipiracilActive Comparator: Bevacizumab: 5 mg /kg, intravenously on days 1,15, every 28 days; Trifluridine/tipiracil: 35 mg/m²orally twice a day on days 1-5 and 8-12, every 28 days. | Drug | Bevacizumab and trifluridine/tipiracil |
Primary outcome
Progression-free survival (PFS)
Time frame: About 3 years
PFS was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first.
4 secondary outcomes
Objective response rate (ORR)
Time frame: About 3 years
Disease control rate (DCR)
Time frame: About 3 years
Overall survival (OS)
Time frame: About 3 years
Adverse Events (AE)
Time frame: About 3 years
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 21 Jan 2026.
- Results publication: PubMed 36623495Nukatsuka M, Fujioka A, Nagase H, Tanaka G, Hayashi H. Evaluation of a Novel Combination Therapy, Based on Trifluridine/Tipiracil and Fruquintinib, against Colorectal Cancer. Chemotherapy. 2023;68(2):102-110. doi: 10.1159/000528867. Epub 2023 Jan 9.
- Results publication: PubMed 38202064Zou J, Wang Y, Xu J, Li J, Wang T, Zhang Y, Bai Y. A Retrospective Study of Trifluridine/Tipiracil with Fruquintinib in Patients with Chemorefractory Metastatic Colorectal Cancer. J Clin Med. 2023 Dec 21;13(1):57. doi: 10.3390/jcm13010057.
- Individual participant dataSharing planned: Yes. IPD shared with other researchers will include the study protocol.
Related trials for Metastatic Colorectal Cancer (CRC)
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
RecruitingPhase 1
A Study Evaluating the Safety and Efficacy of Targeted Therapies in Subpopulations of Patients With Metastatic Colorectal Cancer (INTRINSIC)
Metastatic Colorectal Cancer
Not yet recruitingPhase 2
SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
RecruitingPhase 1
A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
Not yet recruitingPhase 1/2
A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
CRC
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.
Aiping Zhou principal investigator
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fruquintinib Combined With trifluridine/tipiracil and Bevacizumab combined with trifluridine/tipiracil in people with Metastatic Colorectal Cancer (CRC) and Colorectal Cancer, run by Cancer Institute and Hospital, Chinese Academy of Medical Sciences at 1 site in China.
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 11 inclusion and 15 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 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Aiping Zhou (010-67781331, zhouap1825@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free survival (PFS) (time frame: About 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07286695, which also lists 2 linked publications.
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 21 Jan 2026.