Different-Dose SCRT Plus CAPOX, PD-1 Blockade and IL-2 in LARC

Summary

This prospective, randomized phase II trial is designed to evaluate whether low-dose short-course radiotherapy differs from common-dose short-course radiotherapy in terms of efficacy when both regimens are sequentially combined with CAPOX, a PD-1 monoclonal antibody, and interleukin-2 (IL-2) in patients with locally advanced rectal cancer. The study is based on findings from our previous single-center, single-arm PRIDE01 study, in which neoadjuvant short-course radiotherapy followed by systemic chemoimmunotherapy and IL-2 demonstrated encouraging antitumor activity relative to historical short-course radiotherapy-based approaches. The current trial aims to provide more robust clinical evidence regarding the potential role of low-dose radiotherapy combined with IL-2 as a sensitization strategy in multimodal neoadjuvant therapy. By comparing complete response rates between the two radiotherapy dose levels, this study may help define an optimized neoadjuvant approach and support future organ-preservation strategies for patients with locally advanced rectal cancer.

Eligibility

Inclusion Criteria:

1. Male and female patients aged 18 to 70 years.
2. Histologically confirmed rectal adenocarcinoma with the distal margin of the tumor located within 12 cm of the anal verge.
3. MRI-based clinical stage T3-T4 or any T with lymph node-positive (N+) disease.
4. Adequate hematologic, hepatic, and renal function defined as: absolute neutrophil count \>=1.5 x 10\^9/L; platelet count \>=75 x 10\^9/L; serum total bilirubin \<=1.5 x upper normal limit (UNL); aspartate aminotransferase \<=2.5 x UNL; alanine aminotransferase \<=2.5 x UNL; serum creatinine \<=1.5 x UNL.
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

Exclusion Criteria:

1. Metastatic disease (Stage IV).
2. Recurrent rectal cancer.
3. Concurrent active bleeding, perforation, or other complicated conditions requiring emergency surgery.
4. Prior systemic anticancer therapy for rectal cancer.
5. Presence of another non-colorectal neoplastic disease at the same time.
6. Patients with any active autoimmune disease or a history of autoimmune disease requiring steroids or immunomodulatory therapy.
7. Patients with interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, and acute pneumonitis).
8. Any unresolved grade \>=2 toxicity (according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0) resulting from previous treatment, except for anemia, alopecia, and skin hyperpigmentation.
9. Prior treatment with anti-programmed death-1 (PD-1)/PD-L1 antibody or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
10. Pregnant or breastfeeding women.
11. Known or tested positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
12. Known or suspected history of allergy to any of the relevant drugs used in the study.

Conditions3

Interventions1

Related trials

• Neoadjuvant Short-Course Radiotherapy Followed by CAPOX Plus PD-1 Antibody and IL-2 in Locally Advanced Rectal Cancer — The First Affiliated Hospital with Nanjing Medical University

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