High- and Low-dose Radiotherapy Combined With PD-1 Inhibitors for MSS CRLM

Study Overview
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Brief Summary
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This pilot phase I trial aims to investigate the efficacy and safety of high- and low-dose radiotherapy combined with programmed cell death-1 (PD-1) inhibitors in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that have failed second-line immunotherapy or above.

Detailed Description
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This pilot phase I trial aims to investigate the efficacy and safety of high- and low-dose radiotherapy combined with programmed cell death-1 (PD-1) inhibitors in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) that have failed second-line immunotherapy or above. 30 participants will be enrolled in this study. All will take part at Jiangsu Cancer Hospital.

Official Title
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High- and Low-dose Radiotherapy Combined With PD-1 Inhibitors for Microsatellite Stable (MSS) Colorectal Liver Metastases (CRLM)

Conditions
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Colorectal Liver Metastases

Intervention / Treatment
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* Radiation: Radiation: High- and Low-dose radiotherapy
* Drug: PD-1 Inhibitors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with microsatellite stable colorectal liver metastases and failure with second-line or above therapy, and no subsequent standard treatment regimen. Patients with an ECOG score of 0 or 1, and an expected survival period of ≥6 months. During the study, they are willing to follow the arrangement and not use other systemic anti-tumor drugs such as chemotherapy, targeted, Chinese herbal medicine, and proprietary Chinese medicine. 18-70 years old, no gender limit. Exclusion Criteria: Those with a history of severe immediate allergy to the drugs used in this study. Cancer patients who require urgent surgical intervention, such as high-risk pathological fractures, life-threatening bleeding symptoms, etc. Any of the following conditions in the 6 months before screening: myocardial infarction, severe/unstable angina, coronary artery/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient cerebral ischemia Onset or symptomatic pulmonary embolism. Patients with known coronary artery disease, congestive heart failure that does not meet the above criteria or left ventricular ejection fraction <50% must adopt an optimized and stable medical plan determined by the treating doctor. If appropriate, you can consult a cardiologist. Patients with active infection requiring systemic treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High- and Low-dose radiotherapy combined with immunotherapy.<br>All eligible patients will receive high-dose radiotherapy, followed by low-dose radiotherapy combined with PD-1 inhibitor therapy starting within 7 days after completion. The single dose of high-dose radiotherapy will be 6-8 Gy for 3-7 consecutive exposures, and the single dose of low-dose radiotherapy will be 0.5-1.4 Gy for 3-7 consecutive exposures.The PD-1 inhibitor (Zimberelimab) will be administered at the dose recommended in the specification every 3 weeks until disease progression, unacceptable toxicity, and withdrawal of informed consent by the patient. | Radiation: Radiation: High- and Low-dose radiotherapy<br>* High-dose radiotherapy (6-8Gy×3-7F) followed by low-dose radiotherapy (0.5-1.4Gy×3-7F) starting within 7 days after completion.<br>Drug: PD-1 Inhibitors<br>* Immunotherapy (Zimberelimab) is given every three weeks within one week after the end of high-dose radiotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | The proportion of patients showing complete or partial response of low-dose radiotherapy lesions and other metastatic lesions assessed by RECIST v1.1 | 1,3,6, and 12 months after completion of radiotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (PFS) | From the start of treatment to the date of progression or death | 12 months | 
| Overall survival (OS) | the time from the start of treatment to death from any cause | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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microsatellite stable, PD-1 Inhibitors, abscopal effects