Neoadjuvant Arterial Embolization Chemotherapy Combined PD-1 Inhibitor for Locally Advanced Rectal Cancer

Study Overview
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Brief Summary
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Rectal cancer is one of the common malignant tumors of the digestive tract. Some patients with rectal cancer are already advanced tumors when they are first diagnosed. At this time, the tumor has local infiltration, the probability of recurrence and metastasis after surgical resection is high, and even radical tumor resection cannot be performed. Neoadjuvant chemotherapy and radiotherapy have become one of the important treatment methods for these patients to increase the rate of radical tumor resection. However, a series of side effects of neoadjuvant radiotherapy can even continue after the end of radiotherapy, and even increase the incidence of postoperative complications. Superselective arterial interventional chemotherapy has been widely used in preoperative neoadjuvant chemotherapy for various tumors, and its efficacy in rectal cancer has also been confirmed. In addition, as a hot spot in tumor treatment, tumor immunotherapy has shown exciting effects in the NICHE study of neoadjuvant immunotherapy before colon cancer surgery. Moreover, Oxaliplatin is a classic chemotherapeutic drug that induces Immunogenic cell death effects, which induce antitumor immunity. Therefore, in order to optimize the preoperative neoadjuvant therapy plan, the investigators propose a treatment method of superselective arterial chemoembolization combined with immunotherapy and systemic chemotherapy, in order to obtain better preoperative conversion therapy effect and reduce the adverse reactions of neoadjuvant therapy.

Official Title
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Phase Ⅱ Clinical Trial of Neoadjuvant Arterial Embolization Chemotherapy Combined Immune Checkpoint Inhibitor for Locally Advanced Rectal Cancer: A Single Arm Prospective Sturdy

Conditions
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Rectal Neoplasms

Intervention / Treatment
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* Procedure: Arterial chemoembolization
* Drug: Tislelizumab Injection
* Drug: XELOX
* Diagnostic Test: Pelvic MRI
* Procedure: Laparoscopic radical resection of rectal cancer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pathologically confirmed rectal adenocarcinoma (immunohistochemistry, polymerase chain reaction(PCR) or next-generation sequencing(NGS) sequencing methods are acceptable). Magnetic resonance imaging (MRI) measurement of tumor inferior margin ≤12cm from the anus. MRI staging is cT3-4 N0 or cT1-4 N+, no multiple primary cancers or distant metastasis. Life expectancy ≥ 1 year. No anti-tumor therapy, no contraindications to interventional embolization, immunotherapy and chemotherapy. Patients who understand the study protocol and are willing to participate in this study provide written informed consent. Exclusion Criteria: Refuse to participate in this study. Multifocal colorectal cancer. Past history of malignancy, excluding basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ. Inability to receive chemotherapy, such as but not limited to bone marrow suppression, etc. Major organ diseases (such as but not limited to chronic obstructive pulmonary disease, coronary heart disease and renal insufficiency, etc.) during acute exacerbation and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.), American Society of Anesthesiologists(ASA) score > 3. Mental disability or illiteracy or language and communication barriers cannot understand the research protocol. There are contraindications to arterial puncture, such as but not limited to severe arteriosclerosis or even atresia, coagulation dysfunction, long-term use of anticoagulants and cannot be stopped, etc. Obstruction or high risk of obstruction by rectal tumor and/or bleeding and/or perforation. Peripheral sensory nerve disorder, unable to receive oxaliplatin-based chemotherapy. Lateral pelvic lymph node metastasis (mainly supplied by the internal iliac artery). Pregnancy or breastfeeding. Contraindications for MRI。 Consecutive use of corticosteroids for more than 3 days within 1 month before signing the consent form。 MRI assessment was T4b or MRF positive。 Other scenarios deemed inappropriate by the investigators for this study.

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: experimental arm<br> | Procedure: Arterial chemoembolization<br>* The blood supplying artery of the tumor is selected for drug injection with Oxaliplatin 85mg/m2 combined Raltitrexed 3mg/m2. After drug injection, gelatin sponge is used for embolization.<br>Drug: Tislelizumab Injection<br>* Tislelizumab Injection 200mg i.v. q3w, A total of 3 cycles are administered.<br>Drug: XELOX<br>* Capecitabine 1,000 mg/m2 bid, po, on days 1-14 Oxaliplatin: 130 mg/m2, i.v. day 1 Cycles are repeated on day 22. A total of 3 cycles are administered.<br>Diagnostic Test: Pelvic MRI<br>* Pelvic MRI to evaluate efficacy<br>Procedure: Laparoscopic radical resection of rectal cancer<br>* Surgical treatment for patients who meet the surgical conditions<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Imaging Tumor Regression Rate | Tumor regression on imaging after neoadjuvant therapy | From date of the start of drugs treatment until the end of drugs treatment (nearly 3 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathologic Complete Response | There is no histological evidence of malignancy in the primary tumor and metastatic regional lymph nodes, or there is only a carcinoma in situ component | From date of the start of drugs treatment until the operation is completed (nearly 4 weeks) | 
| Disease Free Survival | Time from postoperative disease-free survival to disease recurrence or metastasis | 36 months | 
| Safety (The side effects) | The side effects of this study | 36 months | 
| Pathological Tumor Regression Rate | Tumor regression on pathology after neoadjuvant therapy | From date of the start of drugs treatment until the end of drugs treatment (nearly 3 weeks) |