Rectal Artery Infusion Chemotherapy Combined With Anti-PD1 Antibody for MSS LARC

NCT ID: NCT05307198

Last Updated: 2023-10-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-11
• Study Completion Date: 2025-04-25

Brief Summary

The purpose of this study is to explore whether rectal artery infusion chemotherapy combined with anti-PD1 antibody is an effective neoadjuvant therapy for the microsatellite stable locally advanced rectal cancer.

Detailed Description

Neoadjuvant chemoradiation is the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy can achieve a pathological complete response rate (pCR) of about 20%. However, radiotherapy can cause tissue edema and fibrosis, increasing the risk of anastomotic leakage, resulting in rectal, urinary, and sexual dysfunction. Neoadjuvant chemotherapy or immunotherapy can avoid these adverse reactions, but the pCR rate of chemotherapy is significantly lower than that of neoadjuvant radiotherapy, and immunotherapy is less effective for MSS patients with weak immunogenicity. This study is a prospective, single-arm, single-center trial. The study will enhance the local killing effect of oxaliplatin through rectal artery infusion and induce immunogenic cell death (ICD) to enhance tumor antigen presentation, and then combine anti-PD1 antibody for neoadjuvant therapy. The study will address whether this treatment combination achieves pCR rates that are non-inferior to neoadjuvant RT for MSS-type locally advanced rectal cancer. It is known that the effective rate of oxaliplatin-containing intravenous chemotherapy for colorectal cancer is about 60%. In this study, 2 cycles of XELOX induction chemotherapy were firstly performed to screen out patients who were sensitive to chemotherapy. These patients were then infused with oxaliplatin via the superior rectal artery and oral capecitabine, combined with anti-PD1 antibody therapy for 2 cycles, and then underwent TME surgery. The primary endpoint of the study was the pCR rate.

Conditions

Rectal Neoplasms

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rectal Artery Infusion Chemotherapy

Patients receive 2 cycles of Capecitabine and Oxaliplatin (CapeOx) chemotherapy and evaluated with rectum Magnetic Resonance Imaging (MRI). Patients with more than 20% regression of maximum diameter of rectal tumor in MRI image will entry into next step of rectal artery infusion of Oxaliplatin and oral Capecitabine（1000mg/㎡）with anti-PD1 antibody（200mg）every 3 weeks for 2 cycles.Then those patients will receive rectectomy including anterior resection or abdominoperineal resection by open or laparoscopy with TME.

Group Type: EXPERIMENTAL

Oxaliplatin

Intervention Type: DRUG

Drug: Oxaliplatin Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles.

The dose of oxaliplatin used for rectal artery infusion was uncertain because there were no previous study. We design this study with Oxaliplatin 85mg/㎡for rectal artery infusion chemotherapy in Day 1 every 3 weeks and repeat for 2 cycles, based on intravenous chemotherapy regimens recommended by NCCN（mFolfox6）.If there were severe side effects caused by oxaliplatin observed within first 5 patients, we would decreasing the dose of oxaliplatin depending on the multidisciplinary discussion of researchers.

We acknowledged that our study did not determine the most appropriate dosage of oxaliplatin used for artery infusion, but rather performed a novel therapeutic method for microsatellite stable locally advanced rectal cancer.

Rectectomy

Intervention Type: PROCEDURE

Include anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME).

Capecitabine

Intervention Type: DRUG

Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 4 cycles.

Anti-PD-1 monoclonal antibody

Intervention Type: DRUG

Anti-PD1 antibody 200mg/m2 in Day 2 after Rectal Artery Infusion Chemotherapy. Repeat every 3 weeks for 2 cycles.

Interventions

Oxaliplatin

Drug: Oxaliplatin Oxaliplatin 130mg/m2 for inducing chemotherapy in Day 1 every 3 weeks and repeat for two cycles.

The dose of oxaliplatin used for rectal artery infusion was uncertain because there were no previous study. We design this study with Oxaliplatin 85mg/㎡for rectal artery infusion chemotherapy in Day 1 every 3 weeks and repeat for 2 cycles, based on intravenous chemotherapy regimens recommended by NCCN（mFolfox6）.If there were severe side effects caused by oxaliplatin observed within first 5 patients, we would decreasing the dose of oxaliplatin depending on the multidisciplinary discussion of researchers.

We acknowledged that our study did not determine the most appropriate dosage of oxaliplatin used for artery infusion, but rather performed a novel therapeutic method for microsatellite stable locally advanced rectal cancer.

Intervention Type: DRUG

Rectectomy

Include anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME).

Intervention Type: PROCEDURE

Capecitabine

Oral Capecitabine 1000 mg/m2 twice daily combined with oxaliplatin chemotherapy in Day 1 to Day 14 every 3 weeks and repeat for 4 cycles.

Intervention Type: DRUG

Anti-PD-1 monoclonal antibody

Anti-PD1 antibody 200mg/m2 in Day 2 after Rectal Artery Infusion Chemotherapy. Repeat every 3 weeks for 2 cycles.

Intervention Type: DRUG

Other Intervention Names

Sintilimab

Eligibility Criteria

Inclusion Criteria

• Pathologically diagnosed rectal adenocarcinoma
• Age ≥18 years old and ≤75 years old
• MRI stage T3-4aNany and TanyN1-2, but not T4b and no distant metastasis
• Life expectancy of 1 year The above
• Informed consent, no contraindications to chemotherapy exist
• The distance from the lower edge of the tumor to the anus is between 5cm to 12cm by MRI

Exclusion Criteria

• Refused to participate in this study
• Multifocal colorectal cancer
• Past history of malignant tumors, except for basal cell carcinoma/papillary thyroid carcinoma/various types of carcinoma in situ
• Unable to receive chemotherapy , such as but not limited to bone marrow suppression, etc
• Major organ diseases (such as but not limited to COPD, coronary heart disease and renal insufficiency, etc.) acute attack and or severe acute infectious diseases (such as but not limited to hepatitis, pneumonia and myocarditis, etc.), ASA score> 3
• Mental disorder or illiteracy or language and communication barriers cannot understand the research plan
• There are contraindications to arterial puncture, such as but not limited to severe arteriosclerosis or even atresia, coagulation dysfunction, long-term use of anticoagulant drugs and cannot be stopped, etc
• Rectal tumor has obstruction or high risk of obstruction and or there is bleeding and/or perforation
• Peripheral sensory nerve disorder, unable to receive oxaliplatin chemotherapy
• Lateral pelvic lymph node metastasis (mainly supplied by internal iliac artery)
• Pregnancy or breastfeeding
• Unable to accept MRI examination
• Consecutive use of glucocorticoids for more than 3 days within 1 month before signing the consent form
• Tumor directly invades or adheres to adjacent organs、structures(T4b) or tumor invaded MRF（Mesoretal Fascia）
• Other scenarios deemed inappropriate by the investigators

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jun Li, MD

Role: STUDY_DIRECTOR

Second Affiliated Hospital, School of Medicine, Zhejiang University

Locations

Second Affiliated Hospital of Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

Site Status: RECRUITING

Countries

China

Central Contacts

Li Jun, MD

Role: CONTACT

2307016@zju.edu.cn

+86 13777878061

Jiao Yurong

Role: CONTACT

jiaoyurong@zju.edu.cn

+86 13732206364

Facility Contacts

Yurong Jiao

Role: primary

jiaoyurong1990@163.com

+8613732206364

Other Identifiers

Jun Li

Identifier Type: -

Identifier Source: org_study_id