The goal of this clinical trial is to test whether adding targeted radiation plus cadonilimab immunotherapy to standard second-line chemo works better for adults with colorectal cancer only spread to the peritoneum, and check how safe this combined treatment is. Its main research questions are:
Does the combined treatment slow cancer growth for a longer time than standard chemo alone? What side effects will participants get from the new combination therapy? Researchers will compare the chemo-radiation-immunotherapy combination against standard chemo alone to see if the new plan shrinks tumors and improves outcomes.
Participants will:
Receive either the new combined treatment or standard chemo chosen randomly by chance Visit the hospital regularly for drug infusions, scans and physical exams Complete questionnaires about daily quality of life and report any discomfort
Histopathologically confirmed colorectal adenocarcinoma.
Tumors confirmed pMMR by immunohistochemistry or MSI-L/MSS via gene sequencing.
Metastases limited to peritoneum only, no metastases in other organs.
No moderate or massive ascites; only trivial physiological effusion without drainage requirement.
Prior exposure to any anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody or other agents targeting T-cell co-stimulatory/checkpoint pathways.
Moderate or massive ascites requiring clinical intervention.
Partial or complete symptomatic intestinal obstruction.
Pregnant or breastfeeding women.
Parallel
Second-Line Chemotherapy
DrugAll chemotherapy agents are given by intravenous infusion every 2 weeks with oxaliplatin, leucovorin and continuous infusion fluorouracil, or irinotecan, leucovorin and continuous infusion fluorouracil. Targeted agents bevacizumab or cetuximab can be added per investigator's clinical judgment. Dose adjustments are allowed for myelosuppression, gastrointestinal or other toxicities.
Radiation Therapy
RadiationRadiation target volumes are contoured on fused FAPI PET/CT images for peritoneal masses ≥1 cm. Fraction doses range from 5 Gy to 25 Gy over 5 fractions, modified to meet small intestine organ-at-risk constraints. Radiation is delivered within the first 8 weeks of combined chemoimmunotherapy treatment.
Cadonilimab (AK104)
DrugCadonilimab is a PD-1/CTLA-4 dual-target biologic agent. The fixed dose of 6 mg/kg is infused intravenously once every 2 weeks alongside chemotherapy. Dose delay or permanent discontinuation will be applied for grade 3-4 immune-related adverse events that do not improve with immunosuppressive treatment.
Progression-Free Survival (PFS)
Time from randomization to first documentation of tumor progression (including enlargement of target lesions, new distant metastases, or new onset of ascites) or death from any cause, whichever occurs first, assessed per RECIST v1.1.
Overall Survival (OS)
Survival duration from randomization until death from any cause.
Objective Response Rate (ORR)
The best overall tumor response rate, defined as the proportion of participants achieving confirmed complete response or partial response assessed via imaging based on RECIST 1.1 criteria and verified by multidisciplinary team review.
Disease Control Rate (DCR)
The best overall disease control rate, defined as the proportion of participants with confirmed complete response, partial response or stable disease assessed via imaging based on RECIST 1.1 criteria and verified by multidisciplinary team review.
Treatment-related adverse events
Incidence and severity of treatment side effects graded by NCI CTCAE v6.0.
Change in Peritoneal Cancer Index (PCI)
PCI score reflecting peritoneal tumor burden is measured on FAPI PET/CT images to observe tumor load variations.
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