Actively Recruiting
Node-Sparing Hypofractionated Radiotherapy Plus Chemotherapy and PD-1 Inhibitor in pMMR/MSS High-Risk Locally Advanced Colon Cancer: A Prospective, Randomized, Phase II Trial
Led by Sixth Affiliated Hospital, Sun Yat-sen University · Updated on 2025-12-26
52
Participants Needed
1
Research Sites
330 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Most colorectal cancers are microsatellite stable (MSS) or mismatch repair-proficient (pMMR) subtypes, which show limited efficacy to PD-1 inhibitors. Radiotherapy can enhance the release of tumor-associated antigens, thereby improving the responsiveness of pMMR/MSS colorectal cancers to PD-1 blockade. Tumor-draining lymph nodes (TDLNs) are critical sites where PD-1 inhibitors exert their antitumor effects; however, previous studies have reported that direct radiation-induced damage and fibrosis may impair lymphatic drainage and antitumor immunity. Early reports have demonstrated a remarkable pathological complete response (pCR) rate of 77.8% with lymph node-sparing short-course radiotherapy (25 Gy in 5 fractions) in locally advanced rectal cancer. In metastatic colorectal cancer, single-fraction high-dose irradiation (6-8 Gy) has been shown to induce robust abscopal effects. Based on these findings, our study aims to evaluate whether lymph node-sparing hypofractionated radiotherapy (25 Gy/5F or 24 Gy/4F) followed sequentially by chemotherapy and PD-1 blockade can increase the pCR rate, improve tolerability, and ultimately enhance outcomes in patients with pMMR/MSS high-risk locally advanced colon cancer.
CONDITIONS
Official Title
Node-Sparing Hypofractionated Radiotherapy Plus Chemotherapy and PD-1 Inhibitor in pMMR/MSS High-Risk Locally Advanced Colon Cancer: A Prospective, Randomized, Phase II Trial
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Voluntarily signs a written informed consent form.
- Age 18 to 75 years at enrollment.
- ECOG performance status of 0 or 1.
- Life expectancy greater than 2 years.
- Histologically confirmed colon adenocarcinoma without squamous or sarcomatoid components.
- Tumor biopsy shows pMMR by immunohistochemistry or MSS by genomic testing.
- Imaging shows T4 tumor and/or N+ disease (stage IIB-III) per AJCC 8th edition.
- Evaluated by surgery attending physician and eligible for R0 curative resection.
- No prior systemic or local antitumor therapy for rectal cancer before study treatment.
- Agrees to provide tumor tissue and blood samples for study.
- Adequate organ function including hematologic, renal, hepatic, coagulation, and cardiac parameters.
- Women of childbearing potential must have a negative pregnancy test and agree to use effective contraception.
- Willing and able to comply with scheduled visits, treatment, tests, and study requirements.
You will not qualify if you...
- Suspicious metastatic lesions or unresectable locally advanced disease.
- Other malignancy within 5 years except certain local therapies.
- Use of investigational drug or device within 4 weeks before study drug.
- Intestinal obstruction, perforation, gastrointestinal bleeding, or emergency surgery need.
- Multiple primary colorectal cancers.
- Prior radiotherapy to pelvis or abdomen.
- Inability to swallow tablets or malabsorption syndrome.
- Any prior systemic or local antitumor therapy for locally advanced colon cancer.
- Recent nonspecific immunomodulatory therapy or antitumor Chinese herbal medicines.
- Active autoimmune disease requiring systemic therapy within 2 years.
- History or current pneumonitis or interstitial lung disease.
- Significant bleeding tendency or long-term anticoagulation.
- Uncontrolled comorbid conditions or psychiatric/social issues limiting study compliance.
- Recent serious cardiac events or uncontrolled hypertension.
- Active or past inflammatory bowel disease or chronic diarrhea.
- Recent serious infection or active infection requiring treatment.
- Recent major surgery or severe trauma.
- History of immunodeficiency or current long-term immunosuppressive therapy.
- Known active tuberculosis or syphilis infection.
- History of organ or stem cell transplantation.
- Untreated active hepatitis B or C.
- Live vaccine within 30 days before or planned during study.
- Allergy to study drugs or severe hypersensitivity to monoclonal antibodies.
- Known psychiatric illness, substance abuse, alcoholism, or drug dependence.
- Pregnant or breastfeeding women.
- Any condition that may interfere with study results or participation.
- Diseases or symptoms causing high medical risk or uncertain survival, such as leukemoid reaction, cachexia, or BMI ≤ 18.
AI-Screening
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Trial Site Locations
Total: 1 location
1
The Sixth Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong, China, 510655
Actively Recruiting
Research Team
Y
Yanxin Luo, M.D., Ph.D.
CONTACT
Y
Yikan Cheng, M.D., Ph.D.
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
2
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