Neoadjuvant short-course radiotherapy with IL-2 followed by CAPOX plus PD-1 antibody (sintilimab) and IL-2 for locally advanced rectal cancer

A Single-Center, Single-Arm Study of Neoadjuvant Short-Course Radiotherapy With IL-2 Followed by Sequential Immunotherapy With CAPOX Combined With PD-1 Antibody and IL-2 for Locally Advanced Rectal Cancer

This trial will test whether a short course of radiotherapy with IL-2 followed by CAPOX chemotherapy combined with the PD-1 antibody sintilimab and IL-2 helps people with locally advanced rectal cancer shrink tumors and improve outcomes before surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (other)
• Drugs / interventions: Immunotherapy, chemotherapy
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT06577194 on ClinicalTrials.gov

What this trial studies

This single-center, single-arm Phase 2 study gives patients with locally advanced rectal adenocarcinoma short-course pelvic radiotherapy with concurrent interleukin-2 (IL-2), followed by sequential CAPOX chemotherapy combined with the PD-1 antibody sintilimab and additional IL-2. The protocol aims to enhance tumor immune infiltration and increase pathologic response and sphincter-preservation rates while avoiding the toxicity of full total neoadjuvant therapy. Eligible patients are adults 18–70 with non-metastatic T3-4 or node-positive rectal adenocarcinoma, ECOG 0–1, and adequate organ function; key exclusions include metastatic disease, prior systemic colorectal cancer therapy, active autoimmune disease, and significant interstitial lung disease. Outcomes include safety, pathologic response and surgical resection metrics, with imaging and biomarker sampling to explore immune effects.

Who should consider this trial

Good fit: Ideal candidates are adults 18–70 with newly diagnosed, non-metastatic locally advanced rectal adenocarcinoma (T3-4 or node-positive), ECOG 0–1, and adequate blood, liver and kidney function.

Not a fit: Patients with metastatic (stage IV) disease, prior systemic treatment for colorectal cancer, active autoimmune disease, or significant interstitial lung disease are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, this approach could increase tumor shrinkage before surgery and raise rates of organ (sphincter) preservation and longer-term disease control.

How similar studies have performed: While PD-1 antibodies are effective in MSI-H colorectal cancer, most rectal cancers are microsatellite-stable and have shown limited single-agent immunotherapy responses; combining radiotherapy and immunotherapy is a promising but not yet proven strategy in larger studies.

Eligibility criteria

Inclusion Criteria:

* Males and females aged between 18 and 70 years;
* ECOG (Eastern Cooperative Oncology Group) performance status score of 0 or 1;
* Tumor tissue samples obtained and histologically confirmed as rectal adenocarcinoma;
* Adequate hematological, liver, and kidney functions: neutrophil count ≥ 1.5×10\^9/L; platelet count ≥ 75×10\^9/L; serum total bilirubin ≤ 1.5× upper limit of normal (UNL); aspartate aminotransferase ≤ 2.5× UNL; alanine aminotransferase ≤ 2.5× UNL; serum creatinine ≤ 1.5× UNL.

Exclusion Criteria:

* Metastatic disease (Stage IV);
* Recurrent rectal cancer;
* Concurrent active bleeding, perforation, or other complex situations that cannot be addressed with emergency colostomy surgery alone;
* Previous systemic anti-cancer treatment for colorectal cancer;
* Coexistence of other non-colorectal cancer malignancies;
* Patients with any active autoimmune diseases, or a history of needing steroids or immunosuppressive drugs;
* Patients with interstitial lung disease, non-infectious pneumonia, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, and acute pneumonia);
* Previous treatment-induced any grade 2 or above toxicity reaction (according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5 classification) that has not subsided (excluding anemia, hair loss, and skin pigmentation);
* Previous treatment with anti-programmed death receptor-1 (PD-1) or its ligand (PD-L1) antibodies, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies;
* Pregnant or breastfeeding women;
* Known or tested positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS);
* Known or suspected allergy history to any drugs used in the trial.

Where this trial is running

Nanjing, Jiangsu

• Jiangsu Province Hospital — Nanjing, Jiangsu, China (RECRUITING)

Study contacts

• Study coordinator: Yueming Sun

Conditions: Rectal Cancer, Advanced Solid Tumor, Immunotherapy, Short-course radiotherapy, IL-2