Actively Recruiting
Short-Course Radiotherapy Combined With mFOLFOX6, PD-1 Antibody and Cetuximab or Bevacizumab in High-Risk pMMR/MSS Rectal Adenocarcinoma: A Prospective Multicenter Phase II Study
Led by Sixth Affiliated Hospital, Sun Yat-sen University · Updated on 2025-05-14
49
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new combination treatment for patients with high-risk locally advanced rectal cancer (LARC) who have specific high-risk features such as low rectal tumors, advanced clinical staging, and positive markers indicating higher risk of cancer spread. This prospective, open-label, multicenter Phase II study aims to explore the effectiveness and safety of combining short-course radiotherapy with chemotherapy, immunotherapy, and targeted therapy to improve treatment outcomes and long-term survival for these patients. Participants receive neoadjuvant treatment starting with four cycles of the mFOLFOX6 chemotherapy regimen combined with a PD-1 monoclonal antibody and targeted drugs selected based on RAS/BRAF gene status: cetuximab for patients with wild-type genes and bevacizumab for those with mutations. After the first chemotherapy cycle, patients undergo short-course radiotherapy consisting of five fractions of 5Gy each. Following a minimum 7-day break after radiotherapy, patients continue with three more cycles of chemotherapy combined with immunotherapy and targeted drugs (with bevacizumab omitted in the last cycle for mutation patients). Surgery is planned 8 to 10 weeks after radiotherapy, with the type of surgery determined by imaging assessments. Throughout the study, patients will be closely monitored with clinical imaging and laboratory tests to assess treatment response and safety. The primary outcome is the pathological complete response rate measured after one year. Secondary outcomes include survival rates over three years, cancer recurrence rates, successful complete tumor removal, and treatment toxicities. The study provides a comprehensive evaluation of this combined treatment approach for improving outcomes in high-risk rectal adenocarcinoma patients.
CONDITIONS
Brief Title
SCRT + mFOLFOX6 + PD-1 Antibody + Targeted Therapy for HIgh-Risk pMMR/MSS Rectal Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Written informed consent must be provided before study procedures
- Age between 18 and 75 years
- Histologically or cytologically confirmed pMMR/MSS rectal adenocarcinoma only
- Distance from lower margin of rectal tumor to anal verge 10 cm or less
- Clinical stage with high-risk factors such as cT3Nx, positive extramural vascular invasion (EMVI), or cT4, with or without positive mesorectal fascia (MRF) or EMVI
- No distant metastasis before treatment
- No prior anti-cancer treatments including radiotherapy, chemotherapy, targeted or immunotherapy
- ECOG performance status of 0 or 1
- Peripheral blood counts and liver/kidney function within specified limits tested within 15 days before treatment
- No history of other malignancies; not pregnant or breastfeeding; effective contraception used during study and for 6 months after last dose
You will not qualify if you...
- History of severe drug allergies including platinum agents, 5-FU, LV, or 5-HT3 receptor antagonists
- Participation in other clinical trials within 4 weeks prior to enrollment
- Prior treatment with anti-PD-1, PD-L1, PD-L2, CTLA-4, or other checkpoint inhibitors
- Severe electrolyte abnormalities
- Active gastrointestinal diseases such as ulcers or bleeding tumors not healed or resected
- History of arterial or deep vein thrombosis within 6 months or recent bleeding within 2 months
- Pregnant or breastfeeding women or those unwilling to use contraception during study
- Other active malignancies except treated and disease-free for over 3 years or in situ cancers
- Severe cardiac conditions including certain heart diseases or heart failure class II or higher
- Active infections with fever above 38°C
- Uncontrolled hypercalcemia, hypertension, or diabetes
- Severe lung diseases like interstitial pneumonia or pulmonary fibrosis
- Psychiatric disorders affecting treatment or central nervous system diseases
- Severe complications such as bowel obstruction or organ insufficiency
- Unresolved moderate or higher toxicities from previous treatments
- Any unstable medical condition affecting safety or compliance
- Investigator judgment deeming patient unsuitable for study participation
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 8 to 10 weeks
Participants receive a neoadjuvant treatment phase including four cycles of mFOLFOX6 chemotherapy combined with PD-1 monoclonal antibody and targeted therapy (cetuximab for RAS/BRAF wild-type or bevacizumab for RAS/BRAF mutant). Short-course radiotherapy (SCRT) is administered at a dose of 5Gy × 5 fractions after the first cycle of chemotherapy. At least 7 days after completing radiotherapy, participants continue three additional cycles of chemotherapy combined with PD-1 antibody and targeted therapy (bevacizumab is not used in the last cycle for those receiving it).
4 chemotherapy cycles with concurrent treatments and 5 radiotherapy sessions
Duration - 1 day
Participants undergo surgical resection 8 to 10 weeks after completing short-course radiotherapy. Surgery may be local excision or total mesorectal excision depending on clinical assessment.
1 surgical procedure visit
Duration - Up to 3 years
Participants are monitored after surgery to assess long-term outcomes and safety, including potential adjuvant chemotherapy decided by the attending physician.
Scheduled follow-up visits over 3 years
Trial Site Locations
Total: 1 location
1
Sixth Affiliated Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China, 510065
Actively Recruiting
Research Team
J
Jun Huang, PhD.
F
Fang He, MD.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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