Colorectal CancerPhase 2NCT06356584
Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases
A Phase 2 study testing Immunotherapy (Sintilimab), Targeted Therapy Agent (Fruquintinib) and Radiotherapy (SBRT and LDRT) in people with Colorectal Cancer and Immunotherapy, run by Shandong Cancer Hospital and Institute at 1 site in China.
Trial summary
Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer, Immunotherapy, Radiotherapy
- What is being tested?
- Immunotherapy (Sintilimab), Targeted Therapy Agent (Fruquintinib) and Radiotherapy (SBRT and LDRT)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2024to 1 Oct 2026
- 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
- ECOG PS 0-2
- Histologically confirmed colorectal adenocarcinoma with liver metastases (8th edition AJCC)
- MSS/pMMR subtype
- Previously received standard first- and second-line systemic anti-tumor therapy
- At least one measurable lesion as defined by RECIST 1.1 criteria
- Access to tumor samples for biomarker assessment
Show all 10Show fewer
- Expected survival of ≥3 months
- Normal function of major organ systems (within 14 days before enrollment)
- No systemic corticosteroid treatment within 7 days before treatment initiation, excluding physiological corticosteroid replacement therapy.
- Fertile males or females with the potential for pregnancy must use highly effective contraception methods during the trial.
Who cannot join
- Patients diagnosed with malignancies other than colorectal cancer within 3 years prior to enrollment.
- Participating in an interventional clinical study or receiving other investigational drugs or treatments with study devices within the past 4 weeks before enrollment.
- Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs targeting another T cell co-stimulatory or co-inhibitory receptor (e.g., CTLA-4, OX-40, CD137), fruquintinib, etc.
- Received traditional Chinese medicine or immune-modulating drugs with anti-tumor indications within the past 2 weeks before enrollment (excluding local use for controlling pleural effusion).
- Experienced active autoimmune diseases requiring systemic therapy within the past 2 years before enrollment. Replacement therapy is not considered systemic therapy.
- Diagnosed with immune deficiency or received systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of investigational treatment. After consultation with the sponsor, the use of physiological doses of corticosteroids may be approved.
Show all 9Show fewer
- Received liver radiotherapy within the past 2 weeks before enrollment.
- Known presence of central nervous system metastases and/or carcinomatous meningitis.
- Received systemic corticosteroid therapy within 7 days before enrollment.
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, 1 recruiting
- Recruiting
Jinbo Yue
Jinan, Shandong, 250000
Jin Bo Yue, 0531-67626442 ext. 0531-67626442, Len.Xu@hotmail.com
About this study
Official title: Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases: A Randomized, Controlled, Multicenter Phase II Trial
Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.
Read the detailed description
CRC is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. The rationale for this study stems from the intricate interplay between immunotherapy, targeted therapy, and radiotherapy in CRC management. Previous data suggest a negative correlation between liver metastases and immunotherapy efficacy, necessitating a comprehensive approach integrating multiple treatment modalities. Radiotherapy, particularly stereotactic body radiation therapy, has shown promise in controlling liver tumors and modulating the tumor microenvironment, potentially enhancing immunotherapy responses. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.
- Being tested
- Immunotherapy (Sintilimab), Targeted Therapy Agent (Fruquintinib), Radiotherapy (SBRT and LDRT)
- Keywords
- Colorectal cancer, Immunotherapy, Radiotherapy, Targeted therapy, Liver metastasis
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunotherapy (Sintilimab)Drug
Sintilimab
Targeted Therapy Agent (Fruquintinib)Drug
Fruquintinib
Radiotherapy (SBRT and LDRT)Radiation
SBRT and LDRT
| Study group | Role | What they receive |
|---|---|---|
| Immunotherapy, targert therapy, and radiotherapy | Experimental | For liver oligometastases, high-dose stereotactic body radiation therapy (SBRT) irradiation will be administered to all lesions with a dose fractionation pattern of 40-50 Gy/5F, 60-70 Gy/10F, or 65 Gy/13F. For multiple liver metastases, SBRT plus low-dose radiation therapy (LDRT) will be performed to all lesions. One or more suitable lesions (which will be selected by the physician based on proximity to organs at risk) will undergo SBRT with a dose fractionation pattern of 40-50 Gy/5F, 60-70 Gy/10F, or 65 Gy/13F, and the remaining lesions will undergo LDRT at a total dose of 1-10 Gy at 0.5-2.0 Gy/F. Extrahepatic lesions will be not treated with radiotherapy. Targeted therapy and immunotherapy will be administered one week after the end of radiation therapy. A 21-day treatment cycle of sintilimab (200 mg, D1, once every 3 weeks) will be given intravenously on day 1 of each cycle, and fruquintinib will be given on days 1 to 14. Receives: Drug: Immunotherapy (Sintilimab); Drug: Targeted Therapy Agent (Fruquintinib); Radiation: Radiotherapy (SBRT and LDRT) |
| Immunotherapy and targert therapy | Active comparator | A 21-day treatment cycle of sintilimab (200 mg, D1, once every 3 weeks) will be given intravenously on day 1 of each cycle, and fruquintinib will be given on days 1 to 14. Receives: Drug: Immunotherapy (Sintilimab); Drug: Targeted Therapy Agent (Fruquintinib) |
| Targert therapy | Active comparator | Treatment with fruquintinib (5 mg, po, D1-21, once every 4 weeks) will be given on days 1 through 21 in a 28-day treatment cycle. Receives: Drug: Targeted Therapy Agent (Fruquintinib) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free survival (PFS)
Time from initial drug administration to first radiographic disease progression or death (whichever occurs first).
Measured: 1 year
Secondary outcomes (4)
Overall response rate (ORR)
The proportion of subjects achieving complete response (CR) and partial response (PR) among the total subjects; includes assessment of both irradiated and non-irradiated lesions.
Measured: 1 year
Disease control rate (DCR)
The proportion of subjects achieving complete response (CR), partial response (PR), and stable disease (SD) among the total subjects.
Measured: 1 year
Overall survival (OS)
Time from initial drug administration to death of the subject for any reason.
Measured: 3 year
The incidence and grade of adverse events
Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death.
Measured: 2 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2024
- Study start1 Apr 2024
- Primary completion1 Oct 2026 (estimated)
- Study completion1 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- 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
- 62 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shandong Cancer Hospital and Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jinbo Yue, Shandong Cancer Hospital and Institute
- Investigators
- Jin Bo Yue, Principal investigator, Shandong Cancer Hospital and Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06356584
- Sponsor's protocol ID
- SDZLEC2024-078-01
- Status last verified
- Mar 2026
- First submitted
- 5 Apr 2024
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ma Z, Zhu K, Shi F, Feng R, Jiang S, Dou X, Liu J, Niu Z, Yue J. Sintilimab plus fruquintinib with or without radiotherapy for third-line treatment of colorectal cancer with liver metastases: study protocol for a randomized controlled, multicenter phase II trial. Front Immunol. 2026 May 12;17:1622828. doi: 10.3389/fimmu.2026.1622828. eCollection 2026.
PubMed 42206059
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases: A Randomized, Controlled, Multicenter Phase II Trial
- ClinicalTrials.gov ID
- NCT06356584
- Acronym / sponsor ID
- SDZLEC2024-078-01
- Keywords
- Colorectal cancer, Immunotherapy, Radiotherapy, Targeted therapy, Liver metastasis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 62 participants (estimated)
- Lead sponsor
- Shandong Cancer Hospital and InstituteUniversity, hospital or other
- Study start
- 1 Apr 2024 (actual)
- Primary completion
- 1 Oct 2026 (estimated)
- Study completion
- 1 Oct 2026 (estimated)
- First posted
- 10 Apr 2024 (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.
Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.
Detailed description
CRC is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. The rationale for this study stems from the intricate interplay between immunotherapy, targeted therapy, and radiotherapy in CRC management. Previous data suggest a negative correlation between liver metastases and immunotherapy efficacy, necessitating a comprehensive approach integrating multiple treatment modalities. Radiotherapy, particularly stereotactic body radiation therapy, has shown promise in controlling liver tumors and modulating the tumor microenvironment, potentially enhancing immunotherapy responses. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy, targert therapy, and radiotherapy | Experimental | Drug: Immunotherapy (Sintilimab), Drug: Targeted Therapy Agent (Fruquintinib), Radiation: Radiotherapy (SBRT and LDRT)For liver oligometastases, high-dose stereotactic body radiation therapy (SBRT) irradiation will be administered to all lesions with a dose fractionation pattern of 40-50 Gy/5F, 60-70 Gy/10F, or 65 Gy/13F. For multiple liver metastases, SBRT plus low-dose radiation therapy (LDRT) will be performed to all lesions. One or more suitable lesions (which will be selected by the physician based on proximity to organs at risk) will undergo SBRT with a dose fractionation pattern of 40-50 Gy/5F, 60-70 Gy/10F, or 65 Gy/13F, and the remaining lesions will undergo LDRT at a total dose of 1-10 Gy at 0.5-2.0 Gy/F. Extrahepatic lesions will be not treated with radiotherapy. Targeted therapy and immunotherapy will be administered one week after the end of radiation therapy. A 21-day treatment cycle of sintilimab (200 mg, D1, once every 3 weeks) will be given intravenously on day 1 of each cycle, and fruquintinib will be given on days 1 to 14. |
| Immunotherapy and targert therapy | Active comparator | Drug: Immunotherapy (Sintilimab), Drug: Targeted Therapy Agent (Fruquintinib)A 21-day treatment cycle of sintilimab (200 mg, D1, once every 3 weeks) will be given intravenously on day 1 of each cycle, and fruquintinib will be given on days 1 to 14. |
| Targert therapy | Active comparator | Drug: Targeted Therapy Agent (Fruquintinib)Treatment with fruquintinib (5 mg, po, D1-21, once every 4 weeks) will be given on days 1 through 21 in a 28-day treatment cycle. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- ECOG PS 0-2
- Histologically confirmed colorectal adenocarcinoma with liver metastases (8th edition AJCC)
- MSS/pMMR subtype
- Previously received standard first- and second-line systemic anti-tumor therapy
- At least one measurable lesion as defined by RECIST 1.1 criteria
Key exclusion criteria (9 listed)
- Patients diagnosed with malignancies other than colorectal cancer within 3 years prior to enrollment.
- Participating in an interventional clinical study or receiving other investigational drugs or treatments with study devices within the past 4 weeks before enrollment.
- Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs targeting another T cell co-stimulatory or co-inhibitory receptor (e.g., CTLA-4, OX-40, CD137), fruquintinib, etc.
- Received traditional Chinese medicine or immune-modulating drugs with anti-tumor indications within the past 2 weeks before enrollment (excluding local use for controlling pleural effusion).
- Experienced active autoimmune diseases requiring systemic therapy within the past 2 years before enrollment. Replacement therapy is not considered systemic therapy.
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 |
|---|---|---|
| Immunotherapy (Sintilimab)Sintilimab | Drug | Immunotherapy and targert therapy, Immunotherapy, targert therapy, and radiotherapy |
| Targeted Therapy Agent (Fruquintinib)Fruquintinib | Drug | Immunotherapy and targert therapy, Immunotherapy, targert therapy, and radiotherapy, Targert therapy |
| Radiotherapy (SBRT and LDRT)SBRT and LDRT | Radiation | Immunotherapy, targert therapy, and radiotherapy |
Primary outcome
Progression-free survival (PFS)
Time frame: 1 year
Time from initial drug administration to first radiographic disease progression or death (whichever occurs first).
4 secondary outcomes
Overall response rate (ORR)
Time frame: 1 year
Disease control rate (DCR)
Time frame: 1 year
Overall survival (OS)
Time frame: 3 year
The incidence and grade of adverse events
Time frame: 2 year
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 28 Apr 2026.
- Derived from this study: PubMed 42206059Ma Z, Zhu K, Shi F, Feng R, Jiang S, Dou X, Liu J, Niu Z, Yue J. Sintilimab plus fruquintinib with or without radiotherapy for third-line treatment of colorectal cancer with liver metastases: study protocol for a randomized controlled, multicenter phase II trial. Front Immunol. 2026 May 12;17:1622828. doi: 10.3389/fimmu.2026.1622828. eCollection 2026.
- Individual participant dataSharing planned: No
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.
Jin Bo Yue principal investigator
Shandong Cancer Hospital and Institute
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 Immunotherapy (Sintilimab), Targeted Therapy Agent (Fruquintinib) and Radiotherapy (SBRT and LDRT) in people with Colorectal Cancer and Immunotherapy, run by Shandong Cancer Hospital and Institute 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 10 inclusion and 9 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: looking for participants now, as of the sponsor's last update on 28 Apr 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 Jin Bo Yue, dorctor (0531-67626442 ext. 0531-67626442, Len.Xu@hotmail.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: 1 year). 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 NCT06356584, which also lists 1 linked publication.
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 28 Apr 2026.