Induction Chemotherapy Combined With Neoadjuvant Immunotherapy for MSS Colon Cancer — ICONIC  

Colon Neoplasm Clinical Trial

Official title: Induction Chemotherapy Combined With Neoadjuvant Immunotherapy for MSS Colon Cancer: a Prospective Single-center Multi-arm Open-label Randomized Phase II Study

Status Recruiting

Clinical Trial Summary

This study aims to elucidate the regression effects of neoadjuvant chemotherapy combined with immunotherapy and adjuvant therapy in locally advanced MSS colon cancer.

Clinical Trial Description

The standard treatment for locally advanced colon cancer is surgery followed by adjuvant chemotherapy containing oxaliplatin. The MOSAIC and 16968 studies have shown that approximately 30% of patients experience recurrence and metastasis within 6-7 years after surgery. Neoadjuvant chemotherapy may improve the prognosis of patients with malignant tumors. The significant tumor shrinkage after neoadjuvant therapy indicates a greater likelihood of long-term survival for patients. The OPTICAL and FoxTROT studies have shown that approximately 35% of patients are resistant to oxaliplatin-containing neoadjuvant chemotherapy, with a pCR rate of less than 10% and uncertain survival improvement. In addition, immunotherapy has poor efficacy for microsatellite stable (MSS) patients. Therefore, it is necessary to explore new and effective neoadjuvant treatment modalities for tumor regression.

The study will screen for individuals who are sensitive to oxaliplatin-containing regimens through induction chemotherapy. Immunogenic cell death will be enhanced by oxaliplatin-induced immunogenicity and combined with anti-programmed cell death ligand 1 (PD-L1) monoclonal antibodies for neoadjuvant therapy. In the context of cancer, the role of the intestinal microbiome in mediating immune activation induced by chemotherapy drugs has been demonstrated. Clostridium butyricum will be introduced as an adjuvant to explore the possibility of further increasing the significant response rate of neoadjuvant therapy.

The study will first conduct 2 cycles of Capox induction chemotherapy to screen for patients sensitive to chemotherapy. Patients will be randomized into three cohorts: one chemotherapy standard control cohort (continuing Capox chemotherapy for 2 cycles) and two enhancement design cohorts (Capox chemotherapy + Anti-PD-L1 monoclonal antibody for 2 cycles/Capox chemotherapy + Anti-PD-L1 monoclonal antibody + Clostridium butyricum for 2 cycles), followed by CME surgery. The study's primary endpoint is the proportion of Tumor regression grade(TRG)0/1 in the pathological specimens of surgically resected tumors. ;

Related Conditions & MeSH terms

• Colon Neoplasm
• Colonic Neoplasms

• NCT number: NCT05914389
• Study type: Interventional
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Li Jun, MD
• Phone: +86 13777878061
• Email: 2307016@zju.edu.cn
• Status: Recruiting
• Phase: Phase 2
• Start date: August 2023
• Completion date: August 2030