Short-course radiotherapy then CapeOX and toripalimab, with or without surufatinib, before surgery for high-risk mid-to-low rectal cancer

Efficacy and Safety Comparison of Short-course Radiotherapy Followed by CapeOX Chemotherapy Plus Toripalimab With or Without Concurrent Surufatinib in Neoadjuvant Therapy for Mid-to-low Localized Rectal Cancer of High-risk Criteria

This trial tests whether adding surufatinib to short-course radiotherapy followed by CapeOX chemotherapy plus toripalimab before surgery improves tumor response in adults with high-risk mid-to-low rectal cancer.

Quick facts

• Phase: PHASE2; PHASE3
• Study type: Interventional
• Enrollment: 212 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Hospital of Jilin University (other)
• Drugs / interventions: chemotherapy, radiation, toripalimab, Terizumab, Terriptylimab, surufatinib, Sofantinib, immunotherapy
• Locations: 1 site (Changchun, Jilin)
• Trial ID: NCT07505472 on ClinicalTrials.gov

What this trial studies

The trial compares neoadjuvant short-course radiotherapy followed by four cycles of CapeOX chemotherapy combined with the PD-1 inhibitor toripalimab, delivered either with concurrent surufatinib or without it, in patients with mid-to-low rectal adenocarcinoma and MRI-defined high-risk features. The main goal is to improve pathological complete response rates and to characterize safety in this higher-risk group. Key eligibility includes pMMR/MSS tumors, no distant metastasis, ECOG 0–1, and tumor lower edge within 10 cm of the anal verge. The study is led by The First Hospital of Jilin University and enrolls patients at that site in Changchun, China.

Who should consider this trial

Good fit: Adults 18–75 years old with pathologically confirmed mid-to-low rectal tubular adenocarcinoma, MRI-defined high-risk features (e.g., cT4, cN2, mrMRF+, EMVI+, or lateral lymph node involvement), pMMR/MSS status, no distant metastases, and ECOG 0–1 are the intended participants.

Not a fit: Patients with distant metastatic disease, MSI‑high/dMMR tumors, poor performance status, or uncontrolled viral hepatitis are unlikely to benefit or are excluded from this protocol.

Why it matters

Potential benefit: If successful, the combination could raise rates of complete tumor response before surgery and potentially reduce regional recurrence and distant metastasis in high-risk patients.

How similar studies have performed: Previous trials combining neoadjuvant chemoradiotherapy and immune checkpoint inhibitors have shown promising tumor responses, but adding an anti-angiogenic agent like surufatinib in this high-risk neoadjuvant setting remains less tested.

Eligibility criteria

Inclusion Criteria:

* 1\. Patients and their families are able to understand and willing to participate in this clinical study and sign the informed consent form; 2. Age: 18\~75 years old, male or female; 3. Pathologically confirmed rectal tubular adenocarcinoma; Differentiation into Grade 1-3, i.e., high, intermediate, and low-grade adenocarcinoma; pMMR/MSS phenotype; 4. Medium and low rectal cancer with the lower edge of the tumor located within 10cm from the anal verge; 5. Inclusion of treatment-naïve risk factors: cT4/cN2/mrMRF+/EMVI+ or lateral lymph node involvement.

  6\. No distant metastases; 7. ECOG score 0-1; 8. Hepatitis B surface antigen (HBsAg) (-) and hepatitis B core antibody (HBcAb) (-). If HBsAg (+) or HBcAb (+), hepatitis B virus deoxyribonucleic acid (HBV-DNA) must \< 1000 copies/mL or 200 IU/mL for enrollment; 9. HCV antibody (-); 10. Negative serum or urine pregnancy test for females of childbearing age; 11. Females of childbearing potential or males with potential reproductive partners should agree to use adequate contraception (such as intrauterine devices, birth control pills, or condoms) for the duration of the study and for 120 days after the end of the study; 12. No history of pelvic radiotherapy; 13. No history of surgery or chemotherapy for rectal cancer; 14. Not accompanied by systemic infections requiring antibiotic treatment; 15. Heart, lung, liver, and kidney function can tolerate surgery;

Exclusion Criteria:

* 1\. Recurrent rectal cancer; 2. ECOG score of 2 points or above; 3. Occurrence of cardiovascular and cerebrovascular diseases within 6 months prior to the first dose: cerebrovascular accident/stroke, myocardial infarction, unstable angina, poorly controlled arrhythmias (including QTc interval ≥ 450 ms for males and 470 ms for females≥ (QTc interval is calculated by Fridericia's formula); 4. Presence of NYHA standard grade III.\~IV. cardiac insufficiency or cardiac color ultrasound examination: LVEF (left ventricular ejection fraction) \< 50%; 5. Presence of hypertension (systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥90mmHg) that cannot be controlled by antihypertensive drugs; 6. Urine routine showed that urine protein was ≥++, and 24-hour urine protein was \> 1.0g; 7. History of immunodeficiency, including human immunodeficiency virus (HIV) infection; Other acquired, congenital immunodeficiency diseases; History of organ or bone marrow transplantation; 8. Treatment with a live vaccine within 28 days prior to the first dose, except inactivated viral vaccines for seasonal influenza; 9. Previous and current presence of known active or suspected autoimmune disease (except for patients with hypothyroidism controlled by hormone replacement therapy and type I diabetes mellitus who only require control with insulin replacement therapy); 10. Have active tuberculosis; 11. Patients with previous and current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severe impairment of lung function, etc., which may interfere with the detection and management of suspected drug-related pulmonary toxicity; 12. Previous treatment with other small molecule anti-angiogenic targeted drugs or antibody/drug therapy against immune checkpoints, such as PD-1 inhibitors, PD-L1, CTLA4, etc.; 13. Known history of severe allergy to PD-1 monoclonal antibody active ingredient, TKI inhibitor related components, or any investigational drug excipient; 14. Patients with organ bleeding or bleeding tendency, except for rectal primary tumor bleeding (the investigator needs to assess the bleeding risk); 15. Those who have suffered from malignant tumors in the past; 16. Received other types of anti-tumor or experimental therapy; 17. Pregnant or lactating females; 18. Patients with central nervous system diseases or abnormal mental status, which may affect the patient's participation in this study; 19. Patients with other severe, acute and chronic diseases that may increase the risk of participating in the study and study medication, and are judged by the investigator to be unsuitable for participating in the clinical study;

Where this trial is running

Changchun, Jilin

• the first hospital of Jilin University — Changchun, Jilin, China (RECRUITING)

Study contacts

• Study coordinator: pengyu Chang, Doctor

Conditions: Rectal Cancer, locally advanced rectal cancar, neoadjuvant treatment, short course radiotherapy, Toripalimab, Surufatinib