DEBIRI Combined With Chemotherapy and Bevacizumab in the Treatment of Unresectable Colorectal Cancer Liver Metastases

Study Overview
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Brief Summary
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To study the efficacy and safety of embolization therapy with uniform particle size drug-eluting beads loaded with irinotecan (DEBIRI) in patients with unresectable colorectal cancer liver metastases.

Detailed Description
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Colorectal cancer is the second most common malignant tumor and the fifth cause of cancer death in my country, and its incidence rate is increasing year by year. The liver is the main target organ for hematogenous metastasis of colorectal cancer and the main cause of death in patients with colorectal cancer. About 15% to 25% of patients with colorectal cancer have liver metastases when diagnosed, and another 15% to 25% of patients will develop liver metastases after radical resection of the primary colorectal cancer site. The vast majority (80%) % 90%) of liver metastases cannot be curatively resected initially. The median survival of patients with untreated liver metastases is only 6.9 months, and the 5-year survival rate of patients with unresectable liver metastases is less than 5%. The median survival time of patients who have completely resected liver metastases or reached a state of no evidence of disease is 35 months, and the 5-year survival rate can reach 30% to 57%. For patients with unresectable colorectal cancer liver metastases, the first-line treatment option recommended by the guidelines is multi-agent chemotherapy with or without targeted therapy. Currently, there are limited clinical studies on the use of uniform particle size drug-loaded microspheres combined with chemotherapy drugs and targeted drugs to treat unresectable colorectal cancer liver metastases. Based on this, a single-arm, prospective study is planned to be carried out, using conversion resection rate as the main efficacy indicator, to explore the efficacy of embolization therapy with uniform particle size drug-loaded microspheres loaded with irinotecan combined with systemic chemotherapy and bevacizumab versus systemic chemotherapy combined The efficacy and safety of bevacizumab in the treatment of patients with unresectable colorectal cancer liver metastases provide a more reliable basis for clinical treatment in this field.

Official Title
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A Prospective, Single-arm Clinical Study on the Efficacy and Safety of DEBIRI Combined With Systemic Chemotherapy and Bevacizumab for Unresectable Colorectal Cancer With Liver Metastases

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Combination Product: DEBIRI Combined With Chemotherapy and Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1: Age 18-75, no gender limit 2: Colorectal cancer liver metastasis diagnosed by histopathology/imaging or clinically (refer to the Guidelines for the Diagnosis and Comprehensive Treatment of Colorectal Cancer Liver Metastasis 2023 Edition) 3: The liver is the main target organ for distant metastasis (defined as ≥80% tumor burden limited to the liver) 4: The liver metastasis is determined to be initially unresectable after discussion by the MDT of the research center 5: There is at least one measurable liver metastasis, and the tumor diameter is >1cm (mRECIST assessment) 6: Liver metastases without interventional treatment (TACE, ablation, iodine particle therapy, etc.) 7: The tumor accounts for less than 60% of the total liver 8: The primary tumor is removed or still exists 9: Have not received anti-tumor treatment in the past or it has been more than 1 year since the last anti-tumor treatment 10: Expected survival >3 months 11: Liver function Child-Pugh class A or B 12: ECOG ≤2 points 13: Adequate renal function (creatinine ≤ 2.0mg/dl) 14: Women of childbearing age and men of childbearing potential voluntarily take appropriate contraceptive measures during treatment 15: Understand and sign the informed consent form Exclusion Criteria: 1: Combined with other malignant tumors, except for cervical cancer in situ or cutaneous squamous cell carcinoma that has been fully treated, or basal cell carcinoma of the skin that has been basically controlled, except for colorectal cancer 2: There are any contraindications to TACE treatment 3: Patients eligible for radical treatment (surgery or ablation) 4: Any contraindications to irinotecan: chronic inflammatory bowel disease and/or intestinal obstruction 5: history of severe allergic reaction to irinotecan hydrochloride trihydrate, lactic acid or lactic acid and mannitol or the excipients in this product 6: Severe bone marrow failure 7: history of Gilbert syndrome (no specific testing required) 8: Those with brain metastases or a history of uncontrollable mental illness or severe intellectual or cognitive impairment 9: Severe active infection requiring intravenous antibiotic treatment occurs during the screening period 10: Active bleeding or abnormal coagulation function (PT> 16s, APTT> 43s, INR> 1.5 x ULN), or bleeding tendency or undergoing thrombolytic treatment 11: Patients with serious heart, brain, liver, and kidney system diseases 12: Unstable angina, angioplasty, stent placement or myocardial infarction within 6 months 13: Pregnant or lactating women, and those who are of childbearing potential but refuse to take contraceptive measures 14: Those who are allergic to experimental drugs 15: Patients who cannot comply with the trial protocol or cannot cooperate with follow-up visits 16: Those who the researcher believes are not suitable to participate in this trial

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: DEBIRI<br>After dissolving 100 mg of irinotecan in water for injection or 4 ml of 5% glucose water, use 2 mL of 70 μm uniform particle size microspheres for loading and adsorption for 5 minutes. Then mixed with non-plasma contrast agent to embolize the tumor feeding artery. | Combination Product: DEBIRI Combined With Chemotherapy and Bevacizumab<br>* After dissolving 100 mg of irinotecan in water for injection or 4ml of 5% glucose water.use 2mL of 70μm uniform particle size microspheres for loading and adsorption for 5minutes. Then mixed with non-plasma contrast agent to embolize the tumor feeding artery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| converted resection rate | Discussed and determined by the MDT of the research center. | 1, 3, 6 months after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Actual R0 resection rate | Postoperative pathological examination.No cancer cells can be found at the resection margin of the postoperative specimen under a microscope. There are no cancer cells remaining either to the naked eye or under a microscope, and the lesion has been completely removed. | 1, 3, 6 months after surgery | 
| Progression Free Survival | Time from initiation of treatment to tumor progression or death from any cause, whichever occurs first | 1, 3, 6 months after surgery | 
| Recurrence-free survival | Time from date of curative surgery to recurrence or death | 1, 3, 6 months after surgery | 
| Adverse events | Adverse medical events that occur to subjects during clinical trials | 1, 3, 6 months after surgery |