Actively Recruiting
Node-Sparing Short-Course Radiotherapy Plus Chemotherapy, Bevacizumab and PD-1 Inhibitor in Metastatic pMMR/MSS Colorectal Cancer (MODIFI-CRC)
Led by Sixth Affiliated Hospital, Sun Yat-sen University · Updated on 2025-08-07
286
Participants Needed
1
Research Sites
347 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
The current standard first-line treatment for metastatic colorectal cancer is chemotherapy combined with targeted therapy, yet the prognosis remains poor. Although combining immunotherapy, anti-angiogenic agents, and chemotherapy has shown some efficacy in MSS/pMMR metastatic patients, progression-free survival (PFS) remains suboptimal. Radiotherapy-particularly high-dose radiotherapy-can enhance tumor antigen release and potentially improve the response of MSS/pMMR colorectal cancer to PD-1 inhibitors. Tumor-draining lymph nodes (TDLNs) are key sites for PD-1-mediated anti-tumor activity, but radiation-induced damage and fibrosis may impair their immune function. Prior studies have reported a remarkable pathologic complete response (pCR) rate of 77.8% using node-sparing radiotherapy in locally advanced rectal cancer. This phase II/III study aims to evaluate whether node-sparing modified short-course radiotherapy combined with chemotherapy, bevacizumab, and PD-1 blockade can improve objective response rate (ORR) in phase II and progression-free survival (PFS) in phase III, together with treatment tolerance, and overall prognosis in patients with pMMR/MSS metastatic colorectal cancer.
CONDITIONS
Official Title
Node-Sparing Short-Course Radiotherapy Plus Chemotherapy, Bevacizumab and PD-1 Inhibitor in Metastatic pMMR/MSS Colorectal Cancer (MODIFI-CRC)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Voluntarily signs a written informed consent form
- Aged between 18 and 75 years at enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Expected survival of more than 3 months
- Histologically or cytologically confirmed colorectal adenocarcinoma
- Unsuitable for curative surgery or local treatment, with no prior systemic therapy for recurrent or metastatic disease
- Prior neoadjuvant or adjuvant therapy allowed if recurrence or metastasis occurs at least 12 months after last dose
- At least one measurable lesion per RECIST v1.1 (excluding brain metastases)
- Able to provide 10-20 unstained tumor tissue slides from recent biopsy or archival material within 3 years
- Agrees to provide tumor tissue and blood samples throughout the study
- Adequate organ function with specified 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 study visits, treatments, and tests
You will not qualify if you...
- Known MSI-H or dMMR status
- History of other cancers within 3 years except certain localized skin and breast cancers
- Prior immunotherapy including immune checkpoint inhibitors or immune agonists
- Prior targeted therapies against EGFR or VEGF/VEGFR pathways
- Active or unstable brain metastases; known brainstem, meningeal, or spinal cord metastases
- Symptomatic or recurrent pleural, pericardial effusions, or ascites
- Prior treatment for locally advanced rectal cancer
- Recent use of nonspecific immunomodulators or traditional Chinese medicine
- Active autoimmune disease requiring systemic treatment within 2 years
- History of pneumonitis, interstitial lung disease, bleeding disorders, or long-term anticoagulation
- Uncontrolled comorbidities or cardiovascular conditions affecting safety
- Recent severe gastrointestinal events or thromboembolic events
- Uncontrolled hypertension or recent COPD exacerbation
- Active or prior inflammatory bowel disease
- Serious infections within 4 weeks or active infection requiring systemic antibiotics
- Recent major surgery or significant trauma
- History of immunodeficiency, HIV, or long-term corticosteroid use
- Known active tuberculosis or syphilis
- History of organ or stem cell transplantation
- Untreated active hepatitis B or active hepatitis C
- Recent live vaccination
- Allergy or serious hypersensitivity to study drugs
- Psychiatric disorders, substance abuse, or drug dependence
- Pregnant or breastfeeding women
- Any condition or abnormality interfering with study participation or results
- Tumor invasion of critical organs or vessels with risk of complications
- Presence of free intraperitoneal gas not due to recent procedures
- Continuous anticoagulation within 10 days prior to first dose
- Radiographic evidence of tumor posing bleeding risk due to necrosis or vessel encasement
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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
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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