Short-course radiation followed by liposomal irinotecan, oxaliplatin, capecitabine and sintilimab before surgery for high-risk rectal cancer

Short-Course Radiotherapy Followed by Liposomal Irinotecan, Oxaliplatin, Capecitabine, and Sintilimab as Total Neoadjuvant Therapy in High-Risk Locally Advanced Rectal Cancer: A Single-Arm, Single-Center, Exploratory Study

This treatment plan tests whether a short course of radiation followed by six cycles of liposomal irinotecan, oxaliplatin, capecitabine and the immunotherapy drug sintilimab before surgery can shrink tumors and let some people with newly diagnosed high-risk, locally advanced rectal cancer avoid immediate surgery.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, Sintilimab, radiation
• Locations: 1 site (Wuhan)
• Trial ID: NCT07474103 on ClinicalTrials.gov

What this trial studies

This single-center exploratory study enrolls adults with newly diagnosed high-risk, mid-to-low locally advanced rectal adenocarcinoma that is mismatch repair proficient (MSS/pMMR). All participants receive short-course radiotherapy (25 Gy in 5 fractions) over one week, followed by six cycles of combination chemotherapy (liposomal irinotecan, oxaliplatin, capecitabine) with the PD-1 inhibitor sintilimab. Researchers will monitor tumor response, safety, and the potential to adopt a 'watch-and-wait' nonoperative management approach for patients who achieve a complete clinical response. Eligibility requires no prior antitumor therapy and at least one measurable lesion per RECIST v1.1; outcomes will include response rates and treatment-related adverse events.

Who should consider this trial

Good fit: Ideal candidates are adults 18–75 with newly diagnosed, high-risk mid-low locally advanced rectal adenocarcinoma that is pMMR/MSS, have at least one measurable lesion, no prior antitumor therapy, and can tolerate combined radiotherapy and systemic treatment.

Not a fit: Patients with mismatch repair–deficient/MSI-high tumors, metastatic disease, significant comorbidities that preclude chemo/radiation, prior treatment for this cancer, or low-risk early tumors are unlikely to benefit.

Why it matters

Potential benefit: If successful, the regimen could increase tumor shrinkage before surgery and increase the chance that some patients can safely avoid immediate surgery through a watch-and-wait approach.

How similar studies have performed: Total neoadjuvant therapy and short-course radiotherapy have shown promise in improving response rates for rectal cancer, but adding liposomal irinotecan with a PD-1 inhibitor in pMMR disease is relatively novel and not yet proven.

Eligibility criteria

Inclusion Criteria:

* Voluntary Participation: Subjects voluntarily participate in the study, sign the informed consent form, and have good compliance.
* Age and Gender: Age between 18 and 75 years, any gender.
* Pathological Diagnosis: Histologically or cytologically confirmed rectal adenocarcinoma; confirmed mismatch repair proficient (pMMR) or microsatellite stable (MSS) by genetic testing or immunohistochemistry.
* Disease Stage: Assessed as high-risk, mid-low (distance from the anal verge ≤10 cm) locally advanced rectal cancer by colonoscopy, digital rectal exam, or MRI. High-risk definition: Meeting at least one of the following: cT4, extramural vascular invasion (EMVI), tumor deposits, involvement of the mesorectal fascia or intersphincteric plane.
* Prior Treatment: No prior anti-tumor therapy for this rectal cancer (including surgery, radiotherapy, chemotherapy, immunotherapy, or targeted therapy).
* Measurable Lesion: At least one measurable lesion according to RECIST v1.1 criteria.
* Tumor Tissue Sample: Must provide tumor tissue samples for biomarker analysis.
* Adequate Organ Function (within 7 days before the first dose): 1) Hematological: Hemoglobin ≥90 g/L; White Blood Cell count ≥3.0 x 10⁹/L; Absolute Neutrophil Count ≥1.5 x 10⁹/L; Platelets ≥100 x 10⁹/L. 2) Hepatic: Total Bilirubin \<1.5 x ULN; AST and ALT ≤2.5 x ULN; Albumin ≥30 g/L. 3) Renal: Serum Creatinine ≤1.5 x ULN OR Creatinine Clearance ≥50 mL/min. 4) Coagulation: INR ≤1.5 x ULN (or ≤3 x ULN if on stable anticoagulant therapy); PTT or aPTT ≤1.5 x ULN (or ≤3 x ULN if on stable anticoagulant therapy).
* Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
* Life Expectancy: Expected survival time ≥3 months.
* Good organ function.
* Contraception: Subjects of childbearing potential must agree to use effective contraception during the treatment period and for 6 months after the last dose.

Exclusion Criteria:

* Other Malignancies: Diagnosis of another malignancy within 5 years prior to the first dose, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ, localized prostate cancer, or papillary thyroid cancer, etc.
* Allergy: Known or suspected allergy to the study drugs or any of their excipients.
* Pregnancy and Lactation: Pregnant or lactating women, or women planning to become pregnant during the study or within 6 months after the last dose.
* Central Nervous System Disease: Known active epilepsy, active central nervous system (CNS) metastases, spinal cord compression, carcinomatous meningitis, or leptomeningeal disease.
* Significant Cardiovascular Disease: Clinically significant uncontrolled cardiovascular disease.
* History of Allergic Disease: History of allergic diathesis, asthma, or atopic dermatitis.
* Pleural Effusion/Ascites: Presence of significant pleural effusion or ascites.
* Active Autoimmune Disease: Active autoimmune disease requiring systemic treatment within 2 years prior to the first dose (replacement therapy is allowed).
* Immunosuppressant Use: Use of systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressants within 2 weeks prior to enrollment.
* Interstitial Lung Disease: History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or evidence of active pneumonia on screening chest CT scan.
* Transplantation History: History of allogeneic organ transplantation or hematopoietic stem cell transplantation.
* Active Infection: Positive HIV test result; Active Hepatitis B (HBV DNA ≥10⁴ copies/mL); Active Hepatitis C (HCV RNA ≥10³ copies/mL); Active Tuberculosis.
* Gastrointestinal Risk: History of bowel obstruction within 28 days prior to the first study dose; High risk of gastrointestinal perforation.
* Recent Major Surgery: Major surgical procedure within 4 weeks prior to enrollment.
* Other Exclusionary Conditions: Any other acute or chronic disease, mental disorder, or laboratory abnormality that, in the investigator's judgment, may increase the risk associated with study participation or drug administration, or interfere with the interpretation of study results.

Where this trial is running

Wuhan

• Hongli Liu — Wuhan, China (Recruiting)

Study contacts

• Principal investigator: Hongli Liu, Professor — Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
• Study coordinator: Hongli Liu, Professor

Conditions Rectal Cancer, Adenocarcinoma; total neoadjuvant therapy; Short-Course Radiotherapy; Liposomal Irinotecan; rectal cancer