FAPI-Guided Radiotherapy With Cadonilimab and Standard Chemotherapy for Colorectal Peritoneal Metastasis: A Phase III Randomized Controlled Trial (TORHC-PM02)

FAPI-Guided Hypofractionated Radiotherapy Combined With Cadonilimab and Standard Second-Line Chemotherapy Versus Standard Second-Line Chemotherapy for Peritoneal Metastasis From Colorectal Cancer: A Multicenter, Randomized, Open-Label, Phase III Trial (TORHC-PM02)

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

Inclusion Criteria:

1. Histopathologically confirmed colorectal adenocarcinoma.
2. Tumors confirmed pMMR by immunohistochemistry or MSI-L/MSS via gene sequencing.
3. Metastases limited to peritoneum only, no metastases in other organs.
4. No moderate or massive ascites; only trivial physiological effusion without drainage requirement.
5. No symptomatic intestinal obstruction and no obstructive signs on imaging; patients can take food normally.
6. Baseline CT/MRI confirms peritoneal metastases.
7. Positive baseline FAPI PET/CT: at least one peritoneal mass lesion with long diameter ≥1 cm and markedly elevated SUVmax suitable for radiotherapy contouring.
8. At least one measurable lesion per RECIST v1.1 criteria.
9. Progression after first-line standard systemic therapy (FOLFOX/XELOX ± targeted agents); no prior second-line treatment received.
10. Peritoneal recurrence within 1 year after adjuvant fluoropyrimidine-based chemotherapy.
11. No moderate or massive ascites; only trivial physiological effusion without drainage requirement.
12. Voluntarily sign written informed consent and comply with scheduled study visits and treatment procedures.

Exclusion Criteria:

1. 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.
2. Moderate or massive ascites requiring clinical intervention.
3. Partial or complete symptomatic intestinal obstruction.
4. Pregnant or breastfeeding women.
5. History of high-dose abdominal radiotherapy that prevents re-irradiation.
6. Diffuse miliary peritoneal metastases on FAPI PET/CT without definable target volume for radiotherapy.
7. Active autoimmune diseases (systemic lupus erythematosus, rheumatoid arthritis, etc.); systemic corticosteroids or other immunosuppressants required within 14 days before enrollment; severe underlying vital organ disease judged unsuitable for immunotherapy by investigators.
8. Poor compliance or other conditions judged inappropriate for study participation by investigators.