Colorectal NeoplasmsPhase 2BESTNCT07535632
SBRT Followed by PD-1 Inhibitor, Bevacizumab and TAS-102 as Third-Line Therapy for Recurrent/Metastatic Colorectal Cancer
A Phase 2 study testing SBRT, Sintilimab and Bevacizumab in people with Colorectal Neoplasms, run by Shanghai Zhongshan Hospital at 1 site in China.
Trial summary
This phase II trial studies how well stereotactic body radiotherapy (SBRT) followed by a combination of an immune checkpoint inhibitor (sintilimab), bevacizumab, and trifluridine/tipiracil (TAS-102) works as third-line treatment for patients with recurrent or metastatic colorectal cancer (mCRC) that has progressed… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Neoplasms
- What is being tested?
- SBRT, Sintilimab and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2026to 1 Jun 2028
- 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
- Age 18 to 75 years (inclusive).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Histologically or cytologically confirmed colorectal cancer with unresectable metastatic or recurrent lesions.
- Has received at least first- and second-line systemic anti-tumor therapy for metastatic colorectal cancer (chemotherapy regimens may include fluoropyrimidines, oxaliplatin, irinotecan, with or without targeted agents such as bevacizumab or cetuximab) and has progressed after second-line therapy.
- Has evaluable lung or liver metastases amenable to stereotactic body radiotherapy (SBRT).
- Has at least one measurable lesion according to RECIST v1.1.
- Female patients of childbearing potential must have a negative urine or serum pregnancy test within ≤7 days before first dose of study drug. All fertile patients must agree to use highly effective contraception during the study and for ≥120 days after the last dose.
- Willing and able to provide written informed consent.
Who cannot join
- Laboratory abnormalities: absolute neutrophil count <1.5×10⁹/L, platelet count <100×10⁹/L, hemoglobin <9 g/dL; total bilirubin >1.5× upper limit of normal (ULN) (>2.5× ULN for patients with liver metastases); AST/ALT >2.5× ULN (>5× ULN for patients with liver metastases); serum creatinine >1.5× ULN or creatinine clearance <60 mL/min; APTT or PT >1.5× ULN; albumin <30 g/L; clinically significant electrolyte abnormalities. Transfusion or growth factor support within 2 weeks before enrollment to meet eligibility is not permitted.
- Prior evidence of deficient mismatch repair (dMMR), microsatellite instability-high (MSI-H), or BRAF mutation by histology or ctDNA testing.
- Prior immunotherapy (anti-PD-1, anti-PD-L1, anti-CTLA-4, or any cellular immunotherapy).
- Active or history of autoimmune disease that may relapse.
- Requires systemic corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 14 days before first dose of study drug (exceptions allowed for low-dose steroids, topical/inhaled steroids, or short-term prophylaxis).
- History of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung disease, or poorly controlled systemic disease (e.g., diabetes, hypertension).
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- Clinically uncontrolled diarrhea.
- Severe chronic or active infection requiring systemic antimicrobial therapy, including tuberculosis.
- Brain or leptomeningeal metastases.
- Clinically significant pleural effusion, pericardial effusion, or ascites requiring repeated drainage within 2 weeks before first dose.
- Presence of clinically detectable second primary malignancy or other malignancy within the past 5 years (except adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ).
- Poorly controlled diabetes or electrolyte disturbances despite standard medical management.
- Known HIV infection.
- Untreated chronic hepatitis B (HBV DNA >500 IU/mL) or detectable hepatitis C virus (HCV) RNA. Inactive HBsAg carriers, treated and stable hepatitis B (HBV DNA ≤500 IU/mL), and cured hepatitis C are allowed.
- Major surgery within ≤28 days before first dose.
- Prior allogeneic stem cell or organ transplantation.
- Uncontrolled hypertension (systolic ≥140 mmHg or diastolic >90 mmHg on monotherapy).
- Active gastrointestinal diseases (e.g., duodenal ulcer, ulcerative colitis, intestinal obstruction) or history of intestinal perforation/fistula not fully healed after surgery.
- History of arterial or deep vein thrombosis within 6 months before enrollment, or bleeding tendency/bleeding history within 2 months before enrollment regardless of severity.
- Stroke or transient ischemic attack within 12 months before enrollment; non-healing skin wound, surgical site, trauma, severe mucosal ulcer, or fracture; acute myocardial infarction, severe/unstable angina, or coronary artery bypass graft within 6 months; New York Heart Association (NYHA) class ≥2 heart failure.
- Severe hypersensitivity to other monoclonal antibodies, trifluridine/tipiracil, or any excipient.
- Received systemic chemotherapy within 28 days before first dose, or immunotherapy/hormonal therapy/targeted therapy/investigational therapy within 14 days or 5 half-lives (whichever is shorter).
- Received Chinese herbal medicine or proprietary Chinese medicine for cancer control within 14 days before first dose.
- Toxicities from prior anticancer therapy not recovered to baseline or stable level (except alopecia, neuropathy, and specific laboratory abnormalities deemed not a safety risk).
- Received live vaccine within 4 weeks before first dose.
- Any clinical or laboratory abnormality or compliance issue that, in the investigator's judgment, makes the patient unsuitable for the study.
- Severe psychological or mental abnormalities.
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
Zhongshan Hospital, Fudan University
Shanghai, Shanghai Municipality, 200032
Jian Wang, MD, +86-21-64041990, wang.jian3@zs-hospital.sh.cn
Xian Zhang, MD, +86-21-64041990, zhang.xian2@zs-hospital.sh.cn
About this study
Official title: A Phase II Clinical Study on the Efficacy of Stereotactic Body Radiation Therapy Sequential Combined With Bevacizumab and Trifluridine/Tipiracil in the Treatment of Recurrent Metastatic Colorectal Cancer(BEST)
This phase II trial studies how well stereotactic body radiotherapy (SBRT) followed by a combination of an immune checkpoint inhibitor (sintilimab), bevacizumab, and trifluridine/tipiracil (TAS-102) works as third-line treatment for patients with recurrent or metastatic colorectal cancer (mCRC) that has progressed after at least two prior lines of systemic therapy.
The study will enroll 58 participants at Zhongshan Hospital, Fudan University. Participants will be randomly assigned (1:1) to either the experimental group or the control group. Those in the experimental group will receive SBRT to lung or liver metastases, followed one week later by sintilimab (200 mg every 2 weeks), bevacizumab (5 mg/kg every 2 weeks), and TAS-102 (35 mg/m² twice daily on days 1-5 every 2 weeks). Those in the control group will receive the investigator's choice of standard third-line therapy (such as TAS-102 alone or with bevacizumab, regorafenib, or fruquintinib).
Read more
The main purpose is to see whether the new combination extends the time without the cancer growing or spreading (progression-free survival, PFS). Other goals include measuring overall survival, tumor response rates, local control of treated tumors, abscopal (out-of-field) effects, safety, quality of life, and exploring biomarkers that might predict treatment response.
The study is expected to take 24 months to complete (12 months for enrollment and 12 months for follow-up). Results will help determine if adding SBRT and immunotherapy to standard chemotherapy and anti-angiogenic therapy is a beneficial option for patients with refractory mCRC.
Read the detailed description
Background and Rationale Colorectal cancer (CRC) is the third most common malignancy worldwide. Approximately 40-50% of patients develop metastatic disease (mCRC). For patients who progress after first- and second-line systemic therapy (including fluoropyrimidines, oxaliplatin, irinotecan, and anti-VEGF or anti-EGFR antibodies where indicated), third-line treatment options remain limited. Currently approved agents such as regorafenib, fruquintinib, and trifluridine/tipiracil (TAS-102) provide modest benefit, with median progression-free survival (PFS) of approximately 2-3 months and objective response rates below 5%. Moreover, the vast majority (90-95%) of mCRC patients have microsatellite stable (MSS) or proficient mismatch repair (pMMR) tumors, which are largely unresponsive to immune checkpoint inhibitor monotherapy.
Preclinical and emerging clinical evidence suggests that stereotactic body radiotherapy (SBRT) can induce immunogenic cell death, remodel the tumor immune microenvironment, and synergize with immune checkpoint inhibitors. Additionally, bevacizumab (anti-VEGF) has immunomodulatory effects, including reducing regulatory T cells and M2-type tumor-associated macrophages, and promoting dendritic cell maturation. The phase III SUNLIGHT trial demonstrated that adding bevacizumab to TAS-102 significantly improved overall survival (10.8 vs. 7.5 months) and PFS (5.6 vs. 2.4 months) in refractory mCRC. Therefore, combining SBRT with PD-1 inhibitor, bevacizumab, and TAS-102 may further enhance antitumor immunity and improve clinical outcomes in MSS/pMMR mCRC patients.
Study Design This is a prospective, single-center, randomized, open-label, phase II trial. A total of 58 eligible patients will be randomized 1:1 to either the experimental arm or the control arm. Randomization will be performed using a computer-generated random sequence. No blinding is applied.
Interventions
- Experimental arm: Patients will first receive SBRT to metastatic lung or liver lesions. SBRT is delivered using image-guided radiotherapy. The fractionation schedule is tailored to tumor location, with a biologically effective dose (BED) ≥94 Gy, completed within 1-2 weeks. One week after completion of SBRT, patients start systemic therapy: sintilimab (200 mg intravenously every 2 weeks), bevacizumab (5 mg/kg intravenously every 2 weeks), and TAS-102 (35 mg/m² orally twice daily on days 1-5 of each 14-day cycle). Treatment continues until disease progression, unacceptable toxicity, patient withdrawal, or other protocol-specified discontinuation criteria.
- Control arm: Patients receive investigator's choice of standard-of-care third-line therapy for mCRC, which may include TAS-102 monotherapy, TAS-102 plus bevacizumab, regorafenib, or fruquintinib, according to local clinical practice and Chinese Society of Clinical Oncology (CSCO) guidelines.
Study Duration Enrollment period: 12 months. Total study duration: 24 months (12 months enrollment + 12 months follow-up).
Sample Size Justification Based on historical data, the control arm is expected to have a median PFS of 3 months. The experimental arm is expected to improve median PFS to 7 months. With a two-sided alpha of 0.05 and power of 80%, and accounting for 10% dropout, a total of 58 patients (29 per arm) is required.
Outcome Measures
Primary outcome measure:
- Progression-free survival (PFS), defined as time from randomization to first documented radiographic disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
Secondary outcome measures:
- Overall survival (OS): time from randomization to death from any cause.
- Objective response rate (ORR): proportion of patients achieving complete response (CR) or partial response (PR) per RECIST v1.1.
- Local control rate (irradiated lesions) at 1 year.
- Abscopal response rate (non-irradiated lesions) at 1 year.
- Incidence and severity of adverse events graded according to CTCAE v5.0.
- Quality of life assessed by EORTC QLQ-C30 questionnaire.
Exploratory outcome measures:
- Biomarker analysis, including but not limited to circulating tumor DNA (ctDNA)/molecular residual disease (MRD), PD-L1 expression, tumor mutational burden (TMB), metabolites, and gut microbiota, to explore associations with disease status, radiotherapy resistance, and immunotherapy response.
Statistical Analysis Primary efficacy analysis will be performed on the full analysis set (FAS, intention-to-treat principle), with per-protocol analysis as supportive. PFS and OS will be estimated using the Kaplan-Meier method, and comparisons between arms will be performed using the log-rank test. Hazard ratios and 95% confidence intervals will be calculated using a Cox proportional hazards model. Sensitivity analysis using interval-censored Cox models will be conducted to account for potential bias from irregular imaging assessments. ORR will be compared using Pearson's chi-square test or Fisher's exact test. All statistical tests will be two-sided, with a significance level of 0.05. Statistical analyses will be performed using R software (version 4.1.1 or higher).
Safety Monitoring Adverse events will be collected from the time of informed consent until 30 days after the last dose of study treatment (or 90 days for serious adverse events considered related to study treatment). Safety will be assessed by the principal investigator and reported to the ethics committee according to Chinese regulations. No independent data monitoring committee (DMC) is established for this phase II trial; oversight is provided by the sponsor (Zhongshan Hospital) and the institutional ethics committee.
Ethics and Dissemination This study is approved by the Ethics Committee of Zhongshan Hospital, Fudan University (approval number and date to be inserted). The study will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice, and Chinese regulations. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.
- Conditions
- Colorectal Neoplasms
- Being tested
- SBRT, Sintilimab, Bevacizumab, Trifluridine and Tipiracil Tablets, Standard of Care (Investigator Selected)
- Keywords
- Colorectal Cancer, SBRT, PD-1 inhibitor, Bevacizumab, TAS-102
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
SBRT followed by triple therapy Stereotactic body radiotherapy (SBRT) delivered to metastatic lung or liver lesions using image-guided techniques. Biologically effective dose (BED) ≥94 Gy, completed within 1-2 weeks.
SintilimabDrug
Anti-PD-1 monoclonal antibody administered at 200 mg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity.
BevacizumabDrug
Anti-VEGF monoclonal antibody administered at 5 mg/kg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity.
Trifluridine and Tipiracil TabletsDrug
Oral combination of trifluridine (a thymidine-based nucleoside analog) and tipiracil (a thymidine phosphorylase inhibitor). Given at 35 mg/m² twice daily on days 1-5 of each 14-day cycle until disease progression or unacceptable toxicity.
Standard of Care (Investigator Selected)Drug
Investigator's choice of standard third-line therapy for metastatic colorectal cancer per Chinese Society of Clinical Oncology (CSCO) guidelines. Options may include trifluridine/tipiracil (TAS-102) monotherapy, TAS-102 plus bevacizumab, regorafenib, or fruquintinib. Administered until disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| SBRT followed by triple therapy | Experimental | Patients receive stereotactic body radiotherapy (SBRT) to metastatic lung or liver lesions with a biologically effective dose (BED) ≥94 Gy, completed within 1-2 weeks. One week after SBRT, patients receive sintilimab 200 mg intravenously (IV) every 2 weeks (Q2W), bevacizumab 5 mg/kg IV Q2W, and trifluridine/tipiracil (TAS-102) 35 mg/m² orally twice daily on days 1-5 of each 14-day cycle. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria. Receives: Radiation: SBRT; Drug: Sintilimab; Drug: Bevacizumab; Drug: Trifluridine and Tipiracil Tablets |
| Standard of Care (SOC) | Active comparator | Patients receive investigator's choice of standard-of-care third-line therapy for metastatic colorectal cancer, which may include trifluridine/tipiracil (TAS-102) monotherapy, TAS-102 plus bevacizumab, regorafenib, or fruquintinib, administered according to local clinical practice and Chinese Society of Clinical Oncology (CSCO) guidelines. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria. Receives: Drug: Standard of Care (Investigator Selected) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS)
Time from randomization to first documented radiographic disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
Measured: Up to 24 months
Secondary outcomes (1)
Overall Survival (OS)
Time from randomization to death from any cause.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Apr 2026
- Study start1 Jun 2026 (estimated)
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Shanghai Zhongshan HospitalThe 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
- 58 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Zhongshan Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07535632
- Sponsor's protocol ID
- KY2026100
- Acronym
- BEST
- Status last verified
- Apr 2026
- First submitted
- 10 Apr 2026
- Last updated
- 17 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share IPD due to the exploratory phase II design and lack of a pre-established data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Study on the Efficacy of Stereotactic Body Radiation Therapy Sequential Combined With Bevacizumab and Trifluridine/Tipiracil in the Treatment of Recurrent Metastatic Colorectal Cancer(BEST)
- ClinicalTrials.gov ID
- NCT07535632
- Acronym / sponsor ID
- BEST / KY2026100
- Conditions
- Colorectal Neoplasms
- Keywords
- Colorectal Cancer, SBRT, PD-1 inhibitor, Bevacizumab, TAS-102
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 58 participants (estimated)
- Lead sponsor
- Shanghai Zhongshan HospitalUniversity, hospital or other
- Collaborators
- Innovent Biologics (Suzhou) Co. Ltd.
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 17 Apr 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.
This phase II trial studies how well stereotactic body radiotherapy (SBRT) followed by a combination of an immune checkpoint inhibitor (sintilimab), bevacizumab, and trifluridine/tipiracil (TAS-102) works as third-line treatment for patients with recurrent or metastatic colorectal cancer (mCRC) that has progressed after at least two prior lines of systemic therapy.
The study will enroll 58 participants at Zhongshan Hospital, Fudan University. Participants will be randomly assigned (1:1) to either the experimental group or the control group. Those in the experimental group will receive SBRT to lung or liver metastases, followed one week later by sintilimab (200 mg every 2 weeks), bevacizumab (5 mg/kg every 2 weeks), and TAS-102 (35 mg/m² twice daily on days 1-5 every 2 weeks). Those in the control group will receive the investigator's choice of standard third-line therapy (such as TAS-102 alone or with bevacizumab, regorafenib, or fruquintinib).
The main purpose is to see whether the new combination extends the time without the cancer growing or spreading (progression-free survival, PFS). Other goals include measuring overall survival, tumor response rates, local control of treated tumors, abscopal (out-of-field) effects, safety, quality of life, and exploring biomarkers that might predict treatment response.
The study is expected to take 24 months to complete (12 months for enrollment and 12 months for follow-up). Results will help determine if adding SBRT and immunotherapy to standard chemotherapy and anti-angiogenic therapy is a beneficial option for patients with refractory mCRC.
Detailed description
Background and Rationale Colorectal cancer (CRC) is the third most common malignancy worldwide. Approximately 40-50% of patients develop metastatic disease (mCRC). For patients who progress after first- and second-line systemic therapy (including fluoropyrimidines, oxaliplatin, irinotecan, and anti-VEGF or anti-EGFR antibodies where indicated), third-line treatment options remain limited. Currently approved agents such as regorafenib, fruquintinib, and trifluridine/tipiracil (TAS-102) provide modest benefit, with median progression-free survival (PFS) of approximately 2-3 months and objective response rates below 5%. Moreover, the vast majority (90-95%) of mCRC patients have microsatellite stable (MSS) or proficient mismatch repair (pMMR) tumors, which are largely unresponsive to immune checkpoint inhibitor monotherapy.
Preclinical and emerging clinical evidence suggests that stereotactic body radiotherapy (SBRT) can induce immunogenic cell death, remodel the tumor immune microenvironment, and synergize with immune checkpoint inhibitors. Additionally, bevacizumab (anti-VEGF) has immunomodulatory effects, including reducing regulatory T cells and M2-type tumor-associated macrophages, and promoting dendritic cell maturation. The phase III SUNLIGHT trial demonstrated that adding bevacizumab to TAS-102 significantly improved overall survival (10.8 vs. 7.5 months) and PFS (5.6 vs. 2.4 months) in refractory mCRC. Therefore, combining SBRT with PD-1 inhibitor, bevacizumab, and TAS-102 may further enhance antitumor immunity and improve clinical outcomes in MSS/pMMR mCRC patients.
Study Design This is a prospective, single-center, randomized, open-label, phase II trial. A total of 58 eligible patients will be randomized 1:1 to either the experimental arm or the control arm. Randomization will be performed using a computer-generated random sequence. No blinding is applied.
Interventions
- Experimental arm: Patients will first receive SBRT to metastatic lung or liver lesions. SBRT is delivered using image-guided radiotherapy. The fractionation schedule is tailored to tumor location, with a biologically effective dose (BED) ≥94 Gy, completed within 1-2 weeks. One week after completion of SBRT, patients start systemic therapy: sintilimab (200 mg intravenously every 2 weeks), bevacizumab (5 mg/kg intravenously every 2 weeks), and TAS-102 (35 mg/m² orally twice daily on days 1-5 of each 14-day cycle). Treatment continues until disease progression, unacceptable toxicity, patient withdrawal, or other protocol-specified discontinuation criteria.
- Control arm: Patients receive investigator's choice of standard-of-care third-line therapy for mCRC, which may include TAS-102 monotherapy, TAS-102 plus bevacizumab, regorafenib, or fruquintinib, according to local clinical practice and Chinese Society of Clinical Oncology (CSCO) guidelines.
Study Duration Enrollment period: 12 months. Total study duration: 24 months (12 months enrollment + 12 months follow-up).
Sample Size Justification Based on historical data, the control arm is expected to have a median PFS of 3 months. The experimental arm is expected to improve median PFS to 7 months. With a two-sided alpha of 0.05 and power of 80%, and accounting for 10% dropout, a total of 58 patients (29 per arm) is required.
Outcome Measures
Primary outcome measure:
- Progression-free survival (PFS), defined as time from randomization to first documented radiographic disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
Secondary outcome measures:
- Overall survival (OS): time from randomization to death from any cause.
- Objective response rate (ORR): proportion of patients achieving complete response (CR) or partial response (PR) per RECIST v1.1.
- Local control rate (irradiated lesions) at 1 year.
- Abscopal response rate (non-irradiated lesions) at 1 year.
- Incidence and severity of adverse events graded according to CTCAE v5.0.
- Quality of life assessed by EORTC QLQ-C30 questionnaire.
Exploratory outcome measures:
- Biomarker analysis, including but not limited to circulating tumor DNA (ctDNA)/molecular residual disease (MRD), PD-L1 expression, tumor mutational burden (TMB), metabolites, and gut microbiota, to explore associations with disease status, radiotherapy resistance, and immunotherapy response.
Statistical Analysis Primary efficacy analysis will be performed on the full analysis set (FAS, intention-to-treat principle), with per-protocol analysis as supportive. PFS and OS will be estimated using the Kaplan-Meier method, and comparisons between arms will be performed using the log-rank test. Hazard ratios and 95% confidence intervals will be calculated using a Cox proportional hazards model. Sensitivity analysis using interval-censored Cox models will be conducted to account for potential bias from irregular imaging assessments. ORR will be compared using Pearson's chi-square test or Fisher's exact test. All statistical tests will be two-sided, with a significance level of 0.05. Statistical analyses will be performed using R software (version 4.1.1 or higher).
Safety Monitoring Adverse events will be collected from the time of informed consent until 30 days after the last dose of study treatment (or 90 days for serious adverse events considered related to study treatment). Safety will be assessed by the principal investigator and reported to the ethics committee according to Chinese regulations. No independent data monitoring committee (DMC) is established for this phase II trial; oversight is provided by the sponsor (Zhongshan Hospital) and the institutional ethics committee.
Ethics and Dissemination This study is approved by the Ethics Committee of Zhongshan Hospital, Fudan University (approval number and date to be inserted). The study will be conducted in accordance with the Declaration of Helsinki, Good Clinical Practice, and Chinese regulations. Written informed consent will be obtained from all participants. Results will be disseminated through peer-reviewed publications and presentations at scientific conferences.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| SBRT followed by triple therapy | Experimental | Radiation: SBRT, Drug: Sintilimab, Drug: Bevacizumab, Drug: Trifluridine and Tipiracil TabletsPatients receive stereotactic body radiotherapy (SBRT) to metastatic lung or liver lesions with a biologically effective dose (BED) ≥94 Gy, completed within 1-2 weeks. One week after SBRT, patients receive sintilimab 200 mg intravenously (IV) every 2 weeks (Q2W), bevacizumab 5 mg/kg IV Q2W, and trifluridine/tipiracil (TAS-102) 35 mg/m² orally twice daily on days 1-5 of each 14-day cycle. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria. |
| Standard of Care (SOC) | Active comparator | Drug: Standard of Care (Investigator Selected)Patients receive investigator's choice of standard-of-care third-line therapy for metastatic colorectal cancer, which may include trifluridine/tipiracil (TAS-102) monotherapy, TAS-102 plus bevacizumab, regorafenib, or fruquintinib, administered according to local clinical practice and Chinese Society of Clinical Oncology (CSCO) guidelines. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-specified discontinuation criteria. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Age 18 to 75 years (inclusive).
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
- Histologically or cytologically confirmed colorectal cancer with unresectable metastatic or recurrent lesions.
- Has received at least first- and second-line systemic anti-tumor therapy for metastatic colorectal cancer (chemotherapy regimens may include fluoropyrimidines, oxaliplatin, irinotecan, with or without targeted agents such as bevacizumab or cetuximab) and has progressed after second-line therapy.
- Has evaluable lung or liver metastases amenable to stereotactic body radiotherapy (SBRT).
Key exclusion criteria (27 listed)
- Laboratory abnormalities: absolute neutrophil count <1.5×10⁹/L, platelet count <100×10⁹/L, hemoglobin <9 g/dL; total bilirubin >1.5× upper limit of normal (ULN) (>2.5× ULN for patients with liver metastases); AST/ALT >2.5× ULN (>5× ULN for patients with liver metastases); serum creatinine >1.5× ULN or creatinine clearance <60 mL/min; APTT or PT >1.5× ULN; albumin <30 g/L; clinically significant electrolyte abnormalities. Transfusion or growth factor support within 2 weeks before enrollment to meet eligibility is not permitted.
- Prior evidence of deficient mismatch repair (dMMR), microsatellite instability-high (MSI-H), or BRAF mutation by histology or ctDNA testing.
- Prior immunotherapy (anti-PD-1, anti-PD-L1, anti-CTLA-4, or any cellular immunotherapy).
- Active or history of autoimmune disease that may relapse.
- Requires systemic corticosteroids (>10 mg/day prednisone equivalent) or other immunosuppressive drugs within 14 days before first dose of study drug (exceptions allowed for low-dose steroids, topical/inhaled steroids, or short-term prophylaxis).
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 |
|---|---|---|
| SBRTSBRT followed by triple therapy Stereotactic body radiotherapy (SBRT) delivered to metastatic lung or liver lesions using image-guided techniques. Biologically effective dose (BED) ≥94 Gy, completed within 1-2 weeks. | Radiation | SBRT followed by triple therapy |
| SintilimabAnti-PD-1 monoclonal antibody administered at 200 mg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity. | Drug | SBRT followed by triple therapy |
| BevacizumabAnti-VEGF monoclonal antibody administered at 5 mg/kg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity. | Drug | SBRT followed by triple therapy |
| Trifluridine and Tipiracil TabletsOral combination of trifluridine (a thymidine-based nucleoside analog) and tipiracil (a thymidine phosphorylase inhibitor). Given at 35 mg/m² twice daily on days 1-5 of each 14-day cycle until disease progression or unacceptable toxicity. | Drug | SBRT followed by triple therapy |
| Standard of Care (Investigator Selected)Investigator's choice of standard third-line therapy for metastatic colorectal cancer per Chinese Society of Clinical Oncology (CSCO) guidelines. Options may include trifluridine/tipiracil (TAS-102) monotherapy, TAS-102 plus bevacizumab, regorafenib, or fruquintinib. Administered until disease progression or unacceptable toxicity. | Drug | Standard of Care (SOC) |
Primary outcome
Progression-Free Survival (PFS)
Time frame: Up to 24 months
Time from randomization to first documented radiographic disease progression per RECIST v1.1 or death from any cause, whichever occurs first.
1 secondary outcome
Overall Survival (OS)
Time frame: Up to 36 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 17 Apr 2026.
- Individual participant dataSharing planned: No. No plan to share IPD due to the exploratory phase II design and lack of a pre-established data sharing agreement.
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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.
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 SBRT, Sintilimab and Bevacizumab in people with Colorectal Neoplasms, run by Shanghai Zhongshan Hospital 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 8 inclusion and 27 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 17 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 Jian Wang, MD (+86-21-64041990, wang.jian3@zs-hospital.sh.cn), 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: Up to 24 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 17 Apr 2026.