NCT03698461

Treatment of Colorectal Liver Metastases With Immunotherapy and Bevacizumab

Comparative Analysis of Immune Profile Following Neoadjuvant Chemotherapy in Colorectal Liver Metastases (CRLM): A Prospective Pilot Clinical Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Asan Medical Center · Academic / Other
• Sex: All
• Age: 20 Years
• Healthy volunteers: Not accepted

Summary

Liver is the most common site of metastases from colorectal cancer. Neoadjuvant chemotherapy with targeted agents is usually recommended for borderline-resectable liver metastases that are technically difficult to resect for conversion to resectable disease and control of metastatic spread. However, the prognosis of these patients are still poor, and long term disease-free survival over 3 years is rare and \<20%. More effective measures to prevent recurrence are needed before or after resection of colorectal liver metastases.

Detailed description

* Atezolizumab is a humanized immunoglobulin G1 monoclonal antibody that targets Programmed Death-Ligand 1(PD-L1) and inhibits the interaction between PD-L1 and its receptors, Programmed cell Death protein 1(PD-1) and B7.1. Therapeutic blockade of PD-L1 binding by atezolizumab has been shown to enhance the magnitude and quality of tumor specific T cell responses, resulting in improved anti tumor activity. * Bevacizumab is a recombinant, humanized therapeutic antibody directed against vascular endothelial growth factor(VEGF). In addition to its well-characterized role in angiogenesis, VEGF is also believed to be involved in cancer immune evasion via the induction of myeloid- derived suppressor cells(MDSCs). These VEGF-induced MDSCs can suppress both T-cell and dendritic-cell function. Bevacizumab can restore and/or maintain the antigen presentation capacity of dendritic cells, leading to enhanced T-cell infiltration in tumors. When used in combination, VEGF targeting agents such as bevacizumab promote the normalization of tumor vasculature and may thereby increase access of therapeutic agents. * Atezolizumab with bevacizumab, levoleucovorin, oxaliplatin, and 5-fluorouracil(FOLFOX). A translational study for renal cell carcinoma showed bevacizumab resulted in modulation of tumor immune microenvironment with Th1-related signatures, which was more potentiated by subsequent treatment with atezolizumab. This suggests potentiation of anti-tumor immunity with the combination of bevacizumab and atezolizumab.

Conditions

• Colorectal Neoplasms
• Neoplasm Metastasis
• Colonic Neoplasms
• Rectal Neoplasms

Interventions

Type	Name	Description
DRUG	Atezolizumab	* 1200mg IV on day1 before start of cycle 'atezolizuamb, bevacizumab + FOLFOX(Oxaliplatin, Levoleucovorin, 5-FU') * 840mg IV D1 of C1-12 (Cycle: every 2 weeks)
DRUG	Bevacizumab	5mg/kg IV D1 of C1-12 (Cycle: every 2 weeks) at least 5 minutes after completion of atezolizumab
DRUG	Oxaliplatin	85mg/m2 IV D1 of C1-12 (Cycle: every 2 weeks)
DRUG	Levoleucovorin	200mg/m2 IV D1 of C1-12 (Cycle: every 2 weeks)
DRUG	5-FU	* 5-FU Bolus: 400mg/m2 IV bolus D1 of C1-12 (Cycle: every 2 weeks) * 5-FU infusion: 2400mg/mg continuous IV infusion over 46hours D1-3 of C1-12 (Cycle: every 2 weeks)

Timeline

• Start date: 2019-05-15
• Primary completion: 2021-12-22
• Completion: 2023-10-24
• First posted: 2018-10-09
• Last updated: 2024-01-31

Locations

1 site across 1 country: South Korea