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

NCT07815834 | Not Yet Recruiting Phase 3

• 1 other identifier: FDRT-2026-426-5278
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Colon Rectal Cancer Adenocarcinoma; Peritoneal (Metastatic) Cancer; Second-line Treatment; Radiation Therapy; Immunotherapy

Keywords

Colorectal Peritoneal Metastasis; Radiation Therapy; Fapi; TORCH-PM02

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 36 months after randomization

Secondary Outcomes (5)

• Overall Survival (OS)

  OS is defined from randomization until death from any cause up to 36 months.

• Objective Response Rate (ORR)

  The best overall tumor response will be assessed every 8 weeks after the participant begins study treatment by scheduled MDT assessment through study completion, up to 36 months.

• Disease Control Rate (DCR)

  The best overall disease control rate will be assessed every 8 weeks after the participant begins study treatment by scheduled MDT assessment through study completion, up to 36 months.

• Treatment-related adverse events

  Side effects will be recorded from the participant's first study treatment dose with radiotherapy and system treatment every cycle to 30 days after their final study treatment dose through study completion, up to 36 months.

• Quality of life( QoL)

  At baseline and radiotherapy period will be reorded once, at system treatments QoL will be reported and recorded every 8 weeks regularly during the treatment through study completion, up to 36 months.

Other Outcomes (1)

• Change in Peritoneal Cancer Index (PCI)

  At baseline and every 8 weeks fixed assessment time points during treatment by scheduled MDT assessment through study completion, up to 36 months.

Study Arms (2)

Chemo-immunotherapy plus FAPI-guided radiotherapy

EXPERIMENTAL

Participants receive standard second-line chemotherapy combined with cadonilimab immunotherapy given every two weeks. They also receive hypofractionated radiotherapy guided by FAPI PET/CT to treat peritoneal tumor masses. Radiation doses are adjusted to protect the small intestine. After every eight weeks of treatment, a multidisciplinary team assesses whether surgery is possible. Treatment continues until cancer worsens or side effects become too severe to tolerate.

Drug: Second-Line Chemotherapy; Radiation: Radiation Therapy; Drug: Cadonilimab (AK104)

Standard second-line chemotherapy only

ACTIVE COMPARATOR

Participants receive standard second-line chemotherapy every two weeks. No immunotherapy or radiation treatment is provided in this group. Treatment continues until cancer worsens or side effects become too severe to tolerate. Tumor assessment will be performed after 8 weeks of therapy, a multidisciplinary team assesses whether surgery is possible. Treatment continues until cancer worsens or side effects become too severe to tolerate.

Drug: Second-Line Chemotherapy

Interventions

Second-Line Chemotherapy DRUG

All 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.

Chemo-immunotherapy plus FAPI-guided radiotherapy; Standard second-line chemotherapy only

Radiation Therapy RADIATION

Radiation 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.

Chemo-immunotherapy plus FAPI-guided radiotherapy

Cadonilimab (AK104) DRUG

Cadonilimab 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.

Chemo-immunotherapy plus FAPI-guided radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• No symptomatic intestinal obstruction and no obstructive signs on imaging; patients can take food normally.
• Baseline CT/MRI confirms peritoneal metastases.
• Positive baseline FAPI PET/CT: at least one peritoneal mass lesion with long diameter ≥1 cm and markedly elevated SUVmax suitable for radiotherapy contouring.
• At least one measurable lesion per RECIST v1.1 criteria.
• Progression after first-line standard systemic therapy (FOLFOX/XELOX ± targeted agents); no prior second-line treatment received.
• Peritoneal recurrence within 1 year after adjuvant fluoropyrimidine-based chemotherapy.
• No moderate or massive ascites; only trivial physiological effusion without drainage requirement.
• Voluntarily sign written informed consent and comply with scheduled study visits and treatment procedures.

You may not qualify if:

• 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.
• History of high-dose abdominal radiotherapy that prevents re-irradiation.
• Diffuse miliary peritoneal metastases on FAPI PET/CT without definable target volume for radiotherapy.
• 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.
• Poor compliance or other conditions judged inappropriate for study participation by investigators.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

Location

MeSH Terms

Conditions

Neoplasm Metastasis; Neoplasms

Interventions

Radiotherapy

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Zhen Zhang, MD, PhD

CONTACT

18801735029; zhen_zhang@fudan.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of radiation oncology

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 11, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): August 1, 2030
• Study Completion (Estimated): March 1, 2031
• Last Updated: September 11, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)