Node-Sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor in pMMR/MSS High-Risk Locally Advanced Colon Cancer: A Prospective, Single-Arm, Phase II Trial

NCT07279077 | Recruiting Phase 2 DMC

• 1 other identifier: 2025ZSLYEC-669
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Most colorectal cancers belong to the microsatellite stable (MSS) or proficient mismatch repair (pMMR) subtypes, with limited response to PD-1 inhibitors. Radiotherapy can increase the release of tumor-associated antigens, thereby improve responsiveness to PD-1 blockade in MSS/pMMR rectal cancer. Tumor-draining lymph nodes are important sites for PD-1 inhibitors to exert antitumor effects, and studies have reported that direct radiation-induced damage and fibrosis can inhibit lymph node drainage and anti-tumor function. Accumulating evidence indicates that low-dose radiotherapy reprograms the tumor microenvironment (TME), transforming immunosuppressive 'cold' tumors into immunostimulatory 'hot' tumors. This transition is mediated by modulating the gut microbiota, eliciting innate and adaptive immune responses, inhibiting immunosuppressive cells, and promoting the infiltration of T and B lymphocytes.Therefore, this study aims to evaluate whether node-sparing low-dose radiotherapy (1Gy/8f) concurrent with chemotherapy and PD-1 inhibitor can improve the pathological complete response (pCR) rate, enhance tolerability, and improve prognosis in patients with pMMR/MSS high-risk locally advanced colon cancer.

Conditions

Colon Cancer; Neoadjuvant Therapies; Immune Checkpoint Therapy; Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response(pCR) Rate

  Evaluate whether 8Gy/8F node-sparing low-dose radiotherapy concurrent with chemotherapy and PD-1 inhibitor as total neoadjuvant therapy can better improve the pathological complete response(pCR) rate or not in colon cancer.

  From enrollment to 2-4 weeks after surgery

Secondary Outcomes (7)

• Tumor regression grade (TRG)

  From enrollment to 2-4 weeks after surgery

• Tumor downstaging rate

  From enrollment to 2-4 weeks after finishing preoperative treatment

• R0 resection rate

  From enrollment to 2-4 weeks of surgery

• 3-year overall survival (OS) rate

  From enrollment to 3 years after finishing Surgery

• Event-Free Survival (EFS)

  From enrollment to 3 years after finishing Surgery

Study Arms (1)

Node-sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor

EXPERIMENTAL

D1, D2: Node-sparing low-dose radiotherapy (1GY\*2d) concurrent with chemotherapy (CAPOX) and PD-1 Inhibitor (200mg). 4 cycles, q3w, as total neoadjuvant therapy

Combination Product: Node-Sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor

Interventions

Node-Sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor COMBINATION_PRODUCT

Patients will receive 4 cycles of neoadjuvant therapy: In D1, D2: node-sparing low-dose radiotherapy (1Gy\*2d), concurrent with CAPOX chemotherapy and PD-1 inhibitor(200mg). After that, patients will undergo partial colectomy at the site of tumor.

Node-sparing Low-Dose Radiotherapy Concurrent With Chemotherapy and PD-1 Inhibitor

Eligibility Criteria

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

You may qualify if:

• Voluntarily signed written informed consent.
• Age ≥ 18 years and ≤ 75 years at the time of enrollment.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Life expectancy \> 2 years.
• Histologically confirmed adenocarcinoma of the colon (without squamous or sarcomatoid components).
• Tumor biopsy immunohistochemistry (IHC) indicates pMMR (proficient Mismatch Repair), defined as positive expression of all four proteins: MSH1, MSH2, MSH6, and PMS2; or genetic testing indicates MSS (Microsatellite Stable).
• Staged as T4 and/or N+ (Stage IIB-III) according to the AJCC 8th edition, as evaluated by imaging (contrast-enhanced CT or MRI).
• Prior to enrollment, the subject must be evaluated by a surgeon responsible for the operation based on medical history to confirm eligibility for R0 resection with curative intent.
• No prior systemic or local anti-tumor therapy for colon cancer before study treatment, including radiotherapy, chemotherapy, immunotherapy, biologics, small molecule targeted therapy, etc.
• Subjects agree to the collection of tumor tissue and peripheral blood samples required during the screening period and the study process for use in related research.
• Adequate organ function:
• a) Hematology (no use of blood components or cell growth factors within 7 days prior to the start of study treatment): i. Absolute Neutrophil Count (ANC) ≥ 1.5 × 10⁹/L (1,500/mm³). ii. Platelet count ≥ 100 × 10⁹/L (100,000/mm³). iii. Hemoglobin ≥ 90 g/L. b) Renal: i. Calculated Creatinine Clearance (CrCl) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula: CrCl (mL/min) = {(140 - Age) × Weight (kg) × 0.85 \[if female\]} / (Serum Creatinine (mg/dL) × 72)).
• ii. Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g. c) Hepatic: i. Serum Total Bilirubin (TBil) ≤ 1.5 × ULN (Upper Limit of Normal). ii. AST and ALT ≤ 2.5 × ULN. iii. Serum Albumin (ALB) ≥ 28 g/L. d) Coagulation: i. International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN.
• e) Cardiac Function: i. Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
• Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to study treatment (if the urine test result cannot confirm negativity, a serum pregnancy test is required, and the serum result prevails). If a female subject of childbearing potential engages in sexual activity with a non-sterilized male partner, she must use an acceptable method of contraception starting from screening and agree to continue using it for 120 days after the last dose of the study drug; cessation of contraception after this point should be discussed with the investigator. Periodic abstinence and rhythm methods are not acceptable forms of contraception.

You may not qualify if:

• Presence of suspicious metastatic lesions or locally advanced unresectable disease, regardless of disease stage.
• Subjects who have had other malignancies within 5 years prior to enrollment, excluding colorectal cancer. This excludes subjects with other malignancies cured by local therapy, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the breast.
• Receipt of any investigational drug or investigational device therapy within 4 weeks prior to the first dose of the study drug.
• Presence of intestinal obstruction, bowel perforation, or intestinal bleeding requiring emergency surgical intervention.
• Multiple primary colorectal cancers.
• History of pelvic or abdominal radiotherapy.
• Inability to swallow pills, malabsorption syndrome, or any condition affecting gastrointestinal absorption.
• Prior receipt of any systemic or local anti-tumor therapy for locally advanced colon cancer, including radical surgery, chemotherapy, radiotherapy, immunotherapy (including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy, or any therapy targeting tumor immune mechanisms), biologics, small molecule targeted therapy, etc.
• Receipt of non-specific immunomodulatory therapy (e.g., interleukins, interferons, thymosin, tumor necrosis factor, etc., excluding IL-11 used for thrombocytopenia) within 2 weeks prior to study treatment; receipt of traditional Chinese medicine or herbal preparations with anti-tumor indications within 1 week prior to study treatment.
• Active autoimmune disease requiring systemic treatment (e.g., disease-modifying antirheumatic drugs, corticosteroids, immunosuppressants) within the past two years. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement for adrenal or pituitary insufficiency) is not considered systemic treatment.
• History of non-infectious pneumonitis or pneumonia requiring systemic glucocorticoid treatment, or current history of interstitial lung disease.
• History of severe bleeding tendency or coagulation disorders; patients requiring prior or current long-term anticoagulation therapy (e.g., atrial fibrillation patients meeting CHADS2 score ≥ 2).
• Current uncontrolled comorbidities, including but not limited to decompensated liver cirrhosis, nephrotic syndrome, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, or psychiatric/social conditions that would limit the subject's compliance with study requirements or affect their ability to provide written informed consent.
• History of myocarditis, cardiomyopathy, or malignant arrhythmia.
• Within 12 months prior to study treatment: unstable angina requiring hospitalization, congestive heart failure, or vascular disease (e.g., aortic aneurysm requiring surgical repair or peripheral venous thrombosis), or other cardiac damage that may affect the safety evaluation of the study drug (e.g., poorly controlled arrhythmia, myocardial infarction, or ischemia).

Sponsors & Collaborators

• Sixth Affiliated Hospital, Sun Yat-sen University: lead

Study Sites (1)

The Sixth Affiliated Hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Drug Therapy; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Central Study Contacts

Yanxin Luo, M.D., Ph.D.

CONTACT

+86-20-38254221; luoyx25@mail.sysu.edu.cn

Yikan Cheng, M.D., Ph.D.

CONTACT

15102033641

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PHD

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: December 12, 2025
• Study Start: November 26, 2025
• Primary Completion (Estimated): November 25, 2030
• Study Completion (Estimated): December 30, 2031
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)