Advanced colorectal cancer with liver metastases
Conditions
Interventions
experimental group:Stereotactic Radiotherapy,Iparomlimab and Tuvonralimab Injection
Sponsors
Sir Runrun Shaw Hospital Affiliated to Zhejiang University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1: Histologically or cytologically confirmed colorectal cancer (CRC); 2: Mismatch repair (MMR) protein detection or microsatellite instability (MSI) gene testing of pre-treatment CRC specimens confirms proficient MMR (pMMR) or microsatellite stability (MSS); 3: Patients with CRC liver metastases, with or without extrahepatic disease, who cannot undergo curative treatment via resection and/or local ablation; 4: Patients must have received at least 2 standard treatments for metastatic disease and are expected to be intolerant of subsequent chemotherapy. Past treatment regimens should include oxaliplatin and irinotecan combined with fluoropyrimidines (where applicable) (e.g., FOLFOX, FOLFIRI, or their variants), unless contraindicated, intolerable, or refused. Note: The interval between the last systemic therapy and the first administration of the study drug should be at most 8 weeks. If bevacizumab was administered as part of systemic therapy, a washout period of at least 21 days is required from the last dose to the planned start of local ablation; 5: Patients must have at least 1 liver metastatic lesion measurable by CT/MRI as >=2 cm in at least one dimension (longest diameter). One of the metastatic lesions must be suitable for biopsy and stereotactic body radiation therapy (SBRT); 6: Limited extrahepatic disease is allowed, including up to 2 extrahepatic metastatic sites (e.g., lung, abdomen, pelvis, bone, or local lymph nodes). Each site is counted as 1 site (e.g., two abdominal lesions count as 1 extrahepatic site; 1 lung and 1 abdominal lesion count as 2 sites). Individual extrahepatic lesions should be =18 years; 9: ECOG performance status 0–1. Good patient compliance to attend scheduled hospital follow-ups; 10: Life expectancy >=6 months; 11: No immunotherapy received within 6 months prior to enrollment; 12: Laboratory tests must meet the following standards: a. Absolute neutrophil count >1.5×10?/L, platelet count >=75×10?/L, hemoglobin >=90 g/L. b. INR 50%. e. Proteinuria =2+, 24-hour urine protein quantification should be performed; patients with 50 mL/min or serum creatinine <1.5×ULN. 13: Subjects agree to use effective contraception from the time of signing the informed consent form until 180 days after the last drug administration. Women of childbearing potential must not be pregnant or lactating; 14: Voluntary participation in the study and signing of the informed consent form. If the subject is unable to read or sign the informed consent form due to incapacity, a guardian must act on their behalf to undergo the informed consent process and sign the form. If the subject is illiterate, an eyewitness must witness the informed consent process and sign the form.
Exclusion criteria
Exclusion criteria: 1: Presence of central nervous system (CNS) metastasis, leptomeningeal metastasis, or spinal cord compression caused by metastasis before signing the informed consent; 2: History of radiation therapy to the liver, upper abdomen, or lower chest; 3: Received hepatic embolization and/or ablation therapy within 6 months; 4: Underwent major surgery (as defined by the investigator) within 28 days before the first drug administration; 5: Received PD-1, PD-L1, or CTLA-4 inhibitors (including durvalumab, tremelimumab, or other checkpoint inhibitors) or other immunotherapies within the past 6 months; 6: Active or potentially recurrent autoimmune diseases, except: Vitiligo, alopecia, psoriasis, or eczema not requiring systemic treatment; Hypothyroidism caused by autoimmune thyroiditis requiring only stable-dose hormone replacement therapy; Type 1 diabetes requiring only stable-dose insulin replacement therapy; 7: History of another primary malignancy, except: Malignancies treated with curative intent, with no known active disease and low potential risk of recurrence >=2 years before the first drug administration; Non-melanoma skin cancer or lentigo maligna without disease evidence, fully treated; Carcinoma in situ without disease evidence, fully treated; 8: Child-Pugh class B or higher; 9: Inability to tolerate or refusal of re-immunotherapy; 10: Known allergy or hypersensitivity to any study drug or its excipients; 11: Requirement for systemic corticosteroids (>10 mg prednisone daily or equivalent) or other immunosuppressive drugs (e.g., cyclophosphamide, azathioprine, methotrexate, thalidomide, TNF-a inhibitors, etc.) for treating diseases within 2 weeks before the first drug administration. Local corticosteroids, nasal sprays, and inhaled steroids are permitted. Systemic corticosteroids for preventing contrast agent allergy are allowed; 12: Uncontrolled concurrent diseases, including but not limited to persistent or active infections requiring systemic treatment, symptomatic congestive heart failure, unstable angina, arrhythmia, or mental disorders/social situations that limit compliance with study requirements; 13: History of allogeneic hematopoietic stem cell transplantation or organ transplantation (except corneal transplantation); 14: Received live vaccines within 4 weeks before the first drug administration; 15: Participated in other clinical studies and received investigational products within 4 weeks before the first drug administration; 16: Known history of psychoactive substance abuse, alcoholism, or drug abuse; past history of definite neurological or mental disorders, including epilepsy, dementia, or hepatic encephalopathy, etc; 17: Vulnerable populations, such as critically ill patients, individuals with mental illnesses, cognitive impairment, pregnant women, etc; 18: Other conditions that, in the investigator’s judgment, may increase study-related risks or interfere with the interpretation of study results, making the subject unsuitable for enrollment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| objective tumor response rate;RTOG acute radiation injury grading; | — |
Secondary
| Measure | Time frame |
|---|---|
| progression-free survival;2-year overall survival;Quality of life rating;Disease Control Rate;Lymphocyte subpopulation analysis;Duration of Response; | — |
Countries
China
Contacts
Public ContactXiaonan Sun
Sir Runrun Shaw Hospital Affiliated to Zhejiang University School of Medicine
Outcome results
None listed