An Exploratory Study of Sequential Transarterial Chemoembolization With Lipiodol and Neoadjuvant Chemotherapy in the Treatment of Initial Unresectable Colorectal Cancer (CRC)

Study Overview
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Brief Summary
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This is a prospective, open-labelled study to evaluate the efficacy and safety of sequetial transarterial chemoembolization with lipiodol and neoadjuvant chemotherapy in the treatment of initial unresectable colorectal cancer. The progression-free-survival (PFS) will be evaluated as the primary endpoints.

Official Title
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An Exploratory Study of Sequential Transarterial Chemoembolization With Lipiodol and Neoadjuvant Chemotherapy in the Treatment of Initial Unresectable Colorectal Cancer

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: TACE protocol
* Drug: Neoadjuvant Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has fully understood and voluntarily signed an written Informed Consent and agreed to follow the research plan treatment and visiting plan; Aged >=18 years, <= 85 years; Histologically confirmed initial unresectable colorectal cancer; Eastern Cooperative Oncology Group (ECOG) performance status 0-1; Expected survival period ≥ 3 months; At least one measurable lesion, according to RECIST 1.1; The main function is normal. Exclusion Criteria: Known hypersensitivity to any of the study drugs or excipients; Hypertension that is not controlled by the drug; International normalized ratio (INR) > 1.5 or partially activated prothrombin time (APTT) > 1.5 × ULN; WBC count < 3000 /mm^3; Platlet count < 50000 /mm^3; Poorly controlled diabetes before enrollment; Clinically significant electrolyte abnormalities judged by researchers; Patients with obvious evidence of bleeding tendency or medical history of hematochezia within 3 months before enrollment; Cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe / unstable angina pectoris or coronary artery bypass grafting within 6 months before enrollment; Congestive heart failure, New York Heart Association (NYHA) grade > 2; ventricular arrhythmia requiring drug treatment; LVEF (left ventricular ejection fraction) < 50%; Active infection or serious infection that is not controlled by drug; History of clinically significant hepatic disease (ALT and/or AST >5 times the upper normal limit); Women who are pregnant or lactating; Urinary protein ≥ ++, and the 24-hour urine protein quantification is greater than 1.0g; Have any other disease, metabolic disorder, physical examination anomaly, abnormal laboratory result, or any other conditions, which according to the judgment of the investigator, it is reasonable to suspect that the patient is not suitable for the use of the study drug.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>sequential transarterial chemoembolization with lipiodol and neoadjuvant chemotherapy | Drug: TACE protocol<br>* Transarterial infusion chemotherapy: Oxaliplatin(85mg/m^2)+Raltitrexed(3mg) Chemoembolization: Lipiodol emulsion (lipiodol 10ml+ Oxaliplatin 85mg +Lidocaine 1ml)，The endpoint for embolization was defined as stagnation of blood flow of the posterior mesenteric artery. Intervention cycle：4W; Treatment times: 2. followed by mFOLFOX6<br>|
| Active Comparator: Control group<br>neoadjuvant chemotherapy alone | Drug: Neoadjuvant Chemotherapy<br>* mFOLFOX6, Q2W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PFS | PFS was defined as the time from recruitment to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR | ORR is defined as the percentages of patients, relative to the total of enrolled subjects, achieving a complete (CR) or partial (PR) response, according to RECIST 1.1 criteria | up to 3 years | 
| Overall survival (OS) | The time from recruitment to death due to any cause. | up to 3 years | 
| Pathological response rate (PCR+MPR) | Pathologic complete response (pCR) was defined as absence of viable tumor in the post-treatment surgical specimens and major pathologic response (MPR) was defined as ≤ 10% viable tumor. | up to 3 years |