NCT05307198

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

Rectal Artery Infusion Chemotherapy of Oxaliplatin Plus Capecitabine Combined With Anti-PD1 Antibody After Induction Chemotherapy for Microsatellite Stable Locally Advanced Rectal Cancer：a Prospective Single-arm Phase II Study

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 38 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
DRUG	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.
PROCEDURE	Rectectomy	Include anterior resection or abdominoperineal resection by open or laparoscopy with Total Mesorectal Excision (TME).
DRUG	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.
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.

Timeline

• Start date: 2022-05-11
• Primary completion: 2024-04-25
• Completion: 2025-04-25
• First posted: 2022-04-01
• Last updated: 2023-10-10

Locations

1 site across 1 country: China