SBRT Followed by PD-1 Inhibitor, Bevacizumab and TAS-102 as Third-Line Therapy for Recurrent/Metastatic Colorectal Cancer
- Sponsor
- Shanghai Zhongshan Hospital
- Study ID
- NCT07535632
- Phase
- PHASE2
- Status
- Not Yet Recruiting
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Conditions
Eligibility Criteria
- Sex
- ALL
- Age
- 18 Years - 75 Years
- Healthy Volunteers
- Not accepted
Interventions
- SBRT — RADIATIONSBRT 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.
- Sintilimab — DRUGAnti-PD-1 monoclonal antibody administered at 200 mg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity.
- Bevacizumab — DRUGAnti-VEGF monoclonal antibody administered at 5 mg/kg intravenously every 2 weeks (Q2W) until disease progression or unacceptable toxicity.
- Trifluridine and Tipiracil Tablets — DRUGOral 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) — DRUGInvestigator'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 Details
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.
Key Dates
- First listed
- Apr 17, 2026
- Start date
- Jun 1, 2026
- Status verified
- Apr 2026
- Primary completion
- Jun 1, 2028
- Completion
- Jun 1, 2028
Study Design
- Enrollment
- 58 participants (estimated)
- Allocation
- RANDOMIZED
- Intervention model
- PARALLEL
- Primary purpose
- TREATMENT
Arms
- Experimental: SBRT followed by triple therapyPatients 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.
- Active Comparator: Standard of Care (SOC)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.
Primary Outcome Measure
Progression-Free Survival (PFS) [ Time Frame: Up to 24 months ]
Central Contacts
- Jian Wang, MD+86-21-64041990
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