68Ga-FAPI PET-guided abdominal radiotherapy plus cadonilimab and second-line therapy for colorectal cancer with peritoneal metastases

A Prospective Randomized Controlled Study Comparing 68Ga-FAPI PET-Guided Abdominal Radiotherapy Combined With Second-Line Standard Therapy and Cadonilimab Versus Second-Line Standard Therapy in Colorectal Cancer With Peritoneal Metastasis

This trial will test whether using 68Ga‑FAPI PET to guide abdominal radiotherapy combined with cadonilimab and second‑line treatment helps people with colorectal cancer that has spread to the peritoneum.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: immunotherapy, cabozantinib
• Locations: 2 sites (Shanghai, Shanghai Municipality and 1 other locations)
• Trial ID: NCT07079462 on ClinicalTrials.gov

What this trial studies

This Phase 2 trial compares an imaging‑guided radiotherapy approach combined with immunotherapy and standard second‑line systemic treatment against standard second‑line therapy alone for colorectal cancer with peritoneal metastases. Participants assigned to the experimental arm will receive 68Ga‑FAPI PET to map peritoneal disease and undergo targeted abdominal radiotherapy followed by cadonilimab plus standard second‑line systemic therapy, while the control arm will receive standard second‑line systemic therapy. The primary endpoint is objective response rate; secondary endpoints include disease control rate, duration of response, progression‑free survival, overall survival, and safety. Eligible adults must have histologically or cytologically confirmed peritoneal metastases, have progressed after first‑line therapy, and meet performance status and organ function criteria.

Who should consider this trial

Good fit: Adults (≥18) with histologically or cytologically confirmed colorectal peritoneal metastases who progressed after standard first‑line therapy, have ECOG performance status 0–1, and adequate organ function are the intended participants.

Not a fit: People who previously received immunotherapy, have poor performance status (ECOG >1), or a very limited life expectancy are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, this approach could increase tumor response and prolong progression‑free survival by combining targeted radiotherapy with immunotherapy and standard systemic treatment.

How similar studies have performed: FAPI PET imaging and the concept of combining local radiotherapy with immunotherapy are emerging and have shown promising signals in other cancers, but this specific FAPI‑guided radiotherapy plus cadonilimab approach is novel and not yet established for peritoneal colorectal metastases.

Eligibility criteria

Inclusion Criteria:

* 1\. Age of 18 years or older. 2. Peritoneal metastasis of colorectal cancer confirmed by histological or cytological examination (International Union Against Cancer 8th edition of colorectal cancer staging).

  3\. Progression after receiving standard first-line treatment before enrollment; but excluding any type of immunotherapy.

  4\. Eastern Cooperative Oncology Group (ECOG) score of 0-1, with an expected survival time of more than 6 months.

  5\. ECOG score of 0-1. 6. Expected survival time of ≥ 24 weeks. 7. Laboratory tests for bone marrow, liver and kidney organ functions and coagulation function within 7 days before the first administration were in compliance with the study requirements (no blood transfusion, blood products, use of granulocyte colony-stimulating factor or other hematopoietic stimulating factors for correction within 7 days before the laboratory tests).

  8\. Women with reproductive capacity must have a negative blood pregnancy test result within 7 days before the first administration. Male or female patients with reproductive capacity voluntarily use effective contraceptive methods during the study period and within 6 months after the last study medication, such as double barrier contraceptive methods, condoms, oral or injectable contraceptive drugs, intrauterine devices, abstinence, etc. All female patients will be considered to have reproductive capacity, unless the female patient has naturally menopause, artificial menopause or sterilization (uterus removal, bilateral ovary removal).

  9\. Voluntary enrollment and signing of informed consent form, following the trial treatment plan and visit schedule.

Exclusion Criteria:

* 1\. Absolute neutrophil count (ANC) \< 1.5 × 109/L, or platelet count \< 100 × 109/L (for patients with liver metastasis, platelet count \< 80 × 109/L), or hemoglobin \< 9 g/dL; blood transfusion within 2 weeks prior to enrollment is not allowed to meet the inclusion criteria.

  2\. Serum total bilirubin \> 1.5 times the upper limit of normal (ULN); for patients with liver metastasis, \> 2.5 times ULN.

  3\. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \> 2.5 times ULN, or for patients with liver metastasis, ALT and/or AST \> 5 times ULN.

  4\. Serum creatinine \> 1.5 times ULN, or creatinine clearance rate \< 50 ml/min (calculated according to the Cockcroft-Gault formula).

  5\. Partial thromboplastin time (APTT) or prothrombin time (PT) \> 1.5 times ULN (based on the normal values of the clinical trial center).

  6\. The researcher determines clinically significant severe electrolyte abnormalities.

  7\. Urine protein test of 2+ or above, or 24-hour urine protein quantification ≥ 1.0 g/24h.

  8\. Hypertension that is not well controlled by medication, defined as: systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg.

  9\. The patient currently has active peptic ulcer, ulcerative colitis, or other digestive tract diseases or active bleeding from an unresected tumor, or the researcher determines that it may cause gastrointestinal bleeding or perforation; or if there was a previous gastrointestinal perforation or gastrointestinal fistula, and the patient has not recovered after surgical treatment.

  10\. Within 6 months before enrollment, there is a history of arterial thrombosis or deep vein thrombosis, or within 2 months before enrollment, there is evidence or history of bleeding tendency or history of bleeding, regardless of severity.

  11\. Within 12 months before enrollment, a stroke event or transient ischemic attack occurred.

  12\. Within 6 months before enrollment, heart disease including congestive heart failure, acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass surgery; or NYHA class 2 or above heart dysfunction patients; left ventricular ejection fraction (LVEF) \< 50%.

  13\. Uncontrolled malignant pleural effusion, ascites or pericardial effusion (defined as not being effectively controlled by diuretics or puncture as determined by the researcher).

  14\. Any patient who has received any anti-PD-1 antibody, anti-PD-L1 antibody, anti-PD-L2 antibody or anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody (or any other antibody acting on the T cell co-stimulation or checkpoint pathways) before enrollment.

  15\. Within 4 weeks before enrollment, received any form of radiotherapy. 16. At the screening stage, there is a clinically detectable second primary malignant tumor, or other malignant tumors occurred in the past 5 years, excluding fully treated non-melanoma skin cancer, cervical carcinoma in situ and superficial bladder tumor \[non-invasive tumors, carcinoma in situ and T1 (tumor invasion of the lamina propria)\], if present.

  17\. Known clinical significance of liver disease history, including but not limited to known hepatitis B virus (HBV) infection and positive HBV DNA (≥ 1 × 104/ml); known hepatitis C virus (HCV) infection and positive HCV RNA (≥ 1 × 103/ml), or liver cirrhosis, etc.

  18\. Pregnant or lactating women or women with a possibility of pregnancy who have a positive pregnancy test before the first medication; or female participants who are unwilling to implement strict contraception during the study.

The researcher considers that the subject has any clinical or laboratory abnormalities or non-compliance issues that make them unsuitable to participate in this clinical study.

Where this trial is running

Shanghai, Shanghai Municipality and 1 other locations

• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (Recruiting)
• Fudan University Shanghai Cancer Center — Shanghai, China (Completed)

Study contacts

• Study coordinator: Guoxiang Cai

Conditions Colorectal Cancer; Peritoneal Cancer; FAPI PET