Short-Course Radiotherapy With Tumor-Draining Lymph Node Preservation Followed by PD-1 Inhibitors in pMMR/MSS Stage II-III Rectal Cancer

NCT07394192 | Not Yet Recruiting Phase 2

• 1 other identifier: PKUCH- R11
• Study Type: interventional
• Target: 44
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study aims to evaluate the efficacy (pathological complete response rate) of short-course radiotherapy with preservation of tumor-draining lymph nodes followed by sequential PD-1 inhibitor neoadjuvant therapy in patients with stage II-III pMMR/MSS locally advanced rectal cancer.

Conditions

Rectal Cancer; Radiotherapy; PD-1 Inhibitor

Keywords

short-course radiotherapy; tumor-draining lymph nodes; PD-1 inhibitors; pMMR/MSS; locally advanced rectal cancer

Outcome Measures

Primary Outcomes (1)

• pathologic complete response rate

  Defined as the absence of residual tumor cells in the surgically resected specimen after neoadjuvant therapy, including both the primary site and lymph nodes.

  Perioperative

Secondary Outcomes (11)

• tumor regression grade

  Perioperative

• R0 Resection Rate

  Perioperative

• 30-Day Postoperative Complication Rate

  within the first 30 days after the operation

• 3-Year Local-Regional Recurrence Rate

  3 years following surgery

• 3-Year Distant Metastasis Rate

  3 years following the surgery

Study Arms (1)

Experimental arm

EXPERIMENTAL

Neoadjuvant therapy with short-course radiotherapy that preserves tumor-draining lymph nodes, followed by 4 cycles of PD-1 inhibitors

Radiation: short-course radiotherapy that preserves tumor-draining lymph nodes

Interventions

short-course radiotherapy that preserves tumor-draining lymph nodes RADIATION

Patients with stage II-III pMMR/MSS locally advanced rectal cancer receive neoadjuvant therapy with short-course radiotherapy that preserves tumor-draining lymph nodes, followed by 4 cycles of PD-1 inhibitors

Experimental arm

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years old, regardless of sex.
• Fibrocolonoscopy or digital rectal examination indicates that the distal border of the lesion is located 5-10 cm from the anal verge.
• Pathologically confirmed rectal adenocarcinoma.
• Imaging examinations (including pelvic MRI and chest-abdominal CT) confirm a clinical stage of II/III (cT3-T4aN0 or cT2-4aN+, MRF (-), with no distant metastasis) according to the AJCC Cancer Staging Manual, 8th Edition (2018) (for detailed TNM staging of rectal cancer).
• If N+, metastatic lymph nodes are confined to the mesorectal and superior rectal artery drainage regions, with no lateral pelvic lymph node metastasis.
• ⑥ Confirmed by immunohistochemistry or molecular testing to be mismatch repair proficient (pMMR) or microsatellite stable (MSS).
• ⑦ Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-1 (see Appendix 2 for details).
• ⑧ Meeting the following laboratory criteria: Hemoglobin ≥ 90 g/L, white blood cell count ≥ 3.5 × 10⁹/L; Neutrophil count ≥ 1.5 × 10⁹/L, platelet count ≥ 100 × 10⁹/L; Creatinine ≤ 1.0 × upper limit of normal (ULN), blood urea nitrogen (BUN) ≤ 1.0 × ULN; Alanine aminotransferase (ALT) ≤ 1.5 × ULN; Aspartate aminotransferase (AST) ≤ 1.5 × ULN; Alkaline phosphatase (ALP) ≤ 1.5 × ULN; Total bilirubin (TBIL) ≤ 1.5 × ULN; Urine protein negative; normal coagulation time; normal thyroid function.
• ⑨ Patients with primary rectal cancer must have undergone no surgical interventions (excluding palliative stoma formation), chemotherapy, or other antitumor treatments from the time of diagnosis to enrollment.
• ⑩ The planned radiation field must have no history of prior radiotherapy.
• The patient voluntarily agrees to participate in this study, signs the informed consent form, demonstrates good compliance, and is willing to cooperate with follow-up visits and data provision.

You may not qualify if:

• Previous treatment with anti-PD-1/L1, anti-CTLA-4 immunotherapies, or other investigational immunotherapeutic agents is excluded.
• Patients with severe autoimmune diseases are excluded, including active inflammatory bowel disease (such as Crohn's disease, ulcerative colitis), rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's granulomatosis), etc.
• Patients with symptomatic interstitial lung disease or active infectious/non-infectious pneumonitis are excluded.
• Patients with clinical or imaging evidence of intestinal obstruction or perforation, or those deemed by the investigator to be at high risk of perforation or hemorrhage, are excluded.
• History of other malignancies, excluding curatively treated non-melanoma skin cancer and carcinoma in situ of the cervix, are excluded.
• Patients with severe cardiovascular or cerebrovascular diseases are excluded, including cerebrovascular accidents, transient ischemic attacks, myocardial infarction within 6 months prior to enrollment, or significant vascular diseases (including but not limited to aortic aneurysms requiring surgical repair or recent arterial thrombosis). Also excluded are those with poorly controlled cardiac symptoms or conditions, such as unstable angina, heart failure of New York Heart Association (NYHA) Class II or higher, left ventricular ejection fraction (LVEF) \< 50% on echocardiography, or severe arrhythmias uncontrolled by medication.
• Physical examination findings, clinical laboratory abnormalities, or other uncontrolled conditions that, in the investigator's judgment, may interfere with the study results or increase the patient's risk of treatment complications are excluded.
• Lactating or pregnant women are excluded. ⑨ Patients with congenital or acquired immunodeficiency diseases, including human immunodeficiency virus (HIV) infection, or a history of organ transplantation or allogeneic stem cell transplantation, are excluded.
• ⑩ Known active hepatitis B virus (HBV) infection, hepatitis C virus (HCV) infection, or active tuberculosis are excluded.
• ⑪ Patients with concurrent use of other immunomodulators, chemotherapeutic agents, other investigational drugs, or requiring long-term corticosteroid therapy are excluded.
• ⑫ Patients with psychiatric disorders, substance abuse, or social issues that may affect compliance, as determined upon physician review, are excluded.
• ⑬ Patients with allergies or contraindications to the investigational drug(s) are excluded.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

MeSH Terms

Conditions

Rectal Neoplasms

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

Central Study Contacts

Yangzi Zhang, MD

CONTACT

0086-15210821349; zyzfly77@126.com

Study Design

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

Study Record Dates

• First Submitted: January 18, 2026
• First Posted: February 6, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2031
• Last Updated: February 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share