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

NCT07646639 | Recruiting Phase 2 DMC

• 1 other identifier: PRSYM20260325
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Rectal Cancer; Radiotherapy

Keywords

Immunotherapy; IL-2; Short-course radiotherapy

Outcome Measures

Primary Outcomes (1)

• Complete remission

  Complete remission rate defined as the sum of pathological complete remission (pCR) and clinical complete remission (cCR)

  Two years

Secondary Outcomes (7)

• Event-free survival (EFS)

  Three years

• Disease-free survival rate

  Three years

• Overall survival rate

  Three years

• Locoregional recurrence rate

  Three years

• Distant metastasis rate

  Three years

Study Arms (2)

Short-course standard-dose radiotherapy, IL-2 and Sintilimab Combined with CAPOX

ACTIVE COMPARATOR

Drug: Sintilimab + IL-2 Combined with CAPOX; Radiation: Short-course standard-dose radiotherapy

Short-course low-dose radiotherapy, IL-2 and Sintilimab Combined with CAPOX

EXPERIMENTAL

Drug: Sintilimab + IL-2 Combined with CAPOX; Radiation: Short-course low-dose radiotherapy

Interventions

Sintilimab + IL-2 Combined with CAPOX DRUG

Enhanced immuno-chemotherapy cocktail.

Short-course low-dose radiotherapy, IL-2 and Sintilimab Combined with CAPOX; Short-course standard-dose radiotherapy, IL-2 and Sintilimab Combined with CAPOX

Short-course low-dose radiotherapy RADIATION

A short-course radiotherapy (SCRT, 10Gy/5f)

Short-course low-dose radiotherapy, IL-2 and Sintilimab Combined with CAPOX

Short-course standard-dose radiotherapy RADIATION

A short-course radiotherapy (SCRT, 25Gy/5f)

Short-course standard-dose radiotherapy, IL-2 and Sintilimab Combined with CAPOX

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients aged 18 to 70 years.
• Histologically confirmed rectal adenocarcinoma with the distal margin of the tumor located within 12 cm of the anal verge.
• MRI-based clinical stage T3-T4 or any T with lymph node-positive (N+) disease.
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

You may not qualify if:

• Metastatic disease (Stage IV).
• Recurrent rectal cancer.
• Concurrent active bleeding, perforation, or other complicated conditions requiring emergency surgery.
• Prior systemic anticancer therapy for rectal cancer.
• Presence of another non-colorectal neoplastic disease at the same time.
• Patients with any active autoimmune disease or a history of autoimmune disease requiring steroids or immunomodulatory therapy.
• Patients with interstitial lung disease, non-infectious pneumonitis, or uncontrolled systemic diseases (e.g., diabetes mellitus, hypertension, pulmonary fibrosis, and acute pneumonitis).
• 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.
• Prior treatment with anti-programmed death-1 (PD-1)/PD-L1 antibody or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody.
• Pregnant or breastfeeding women.
• Known or tested positive for human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS).
• Known or suspected history of allergy to any of the relevant drugs used in the study.

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

Jiangsu Province Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

sintilimab; Radiotherapy

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Yueming Sun

CONTACT

025-68306026; jssym@vip.sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2025
• First Posted: June 15, 2026
• Study Start: May 20, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)