SBRT Followed by PD-1 Inhibitor, Bevacizumab and TAS-102 as Third-Line Therapy for Recurrent/Metastatic Colorectal Cancer

NCT07535632 | Not Yet Recruiting Phase 2

• 1 other identifier: KY2026100
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Colorectal Neoplasms

Keywords

Colorectal Cancer, SBRT, PD-1 inhibitor, Bevacizumab, TAS-102

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 24 months

Secondary Outcomes (1)

• Overall Survival (OS)

  Up to 36 months

Study Arms (2)

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.

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.

Drug: Standard of Care (Investigator Selected)

Interventions

SBRT RADIATION

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.

SBRT followed by triple therapy

Sintilimab DRUG

Anti-PD-1 monoclonal antibody administered at 200 mg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity.

SBRT followed by triple therapy

Bevacizumab DRUG

Anti-VEGF monoclonal antibody administered at 5 mg/kg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity.

SBRT followed by triple therapy

Trifluridine and Tipiracil Tablets DRUG

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.

SBRT followed by triple therapy

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.

Standard of Care (SOC)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Innovent Biologics (Suzhou) Co. Ltd.: collaborator

Study Sites (1)

Zhongshan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

sintilimab; Bevacizumab; Trifluridine; tipiracil; Standard of Care

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Central Study Contacts

Jian Wang, MD

CONTACT

+86-21-64041990; wang.jian3@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: April 17, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)