The Combination of Immunotherapy and Stereotactic Ablative Radiotherapy in MSS Oligometastatic Colorectal Cancer

Colorectal Cancer Clinical Trial

Official title: Phase II Trial of Multisite Stereotactic Ablative Radiotherapy (SABR) Combined With Sintilimab for Microsatellite Stable (MSS) Oligometastatic Colorectal Cancer

Status Recruiting

Clinical Trial Summary

This is a prospective, single-center, single-arm phase II clinical trial. This study aims to evaluate the safety and tolerability of stereotactic ablative radiotherapy (SABR) in combination with Sintilimab, and to examine the impact of the combination therapy on tumor control, long-term survival and quality of life in patients with microsatellite stable (MSS) oligometastatic colorectal cancer.

A total of 60 MSS oligometastatic colorectal cancer patients will be recruited and receive multisite SABR followed by immunotherapy of Sintilimab within one week from completion. Sintilimab will be given at a fixed dose of 200mg (100mg if weight < 50 kg) via intravenous infusion on the first day of each cycle, repeated every three weeks. The dosing will continue for up to two years until disease progression, unacceptable toxicity or patient withdrawal. The tumor regression, disease control, adverse events and long-term survival will be analyzed.

Clinical Trial Description

Immune-checkpoint inhibitor (ICI) has led to a paradigm shift in the treatment of patients with metastatic cancer, as proved by improved survival and durable responses in a group of these patients. However, the response rates to ICI when given alone are limited. In gastrointestinal cancer, patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors shown a response rate of approximately 40% to ICI, while patients with microsatellite stable (MSS) or mismatch repair-proficient (pMMR) tumors respond poorly to ICI. Such observations have spurred efforts to expand the benefit of immunotherapy, especially in these immune "non-sensitive" tumors, by combining ICI with treatments that induce T-cell associated immune response such stereotactic ablative radiotherapy (SABR).

High-dose ablative radiation was showed to facilitate immunotherapy through promote the activation of innate and adaptive immune responses against tumors in preclinical model and early phase clinical trials. However, a large portion of trials which were launched to test the efficacy of radiotherapy and immunotherapy produced suboptimal results. One important reason could be that majority of these trails were designed with single lesion irradiation, which is insufficient to unveil enough tumor antigens and/or to break the barrier of immunosuppressive tumor microenvironment (TME).

The investigators hypothesized that irradiation to multiple or all sites of diseases is more likely to produce an optimized regimen with ICI by broadly stimulate anti-tumor immunity and reduce tumor burden. Therefore, this study plans to administrate SABR to as many metastatic lesions as possible, in combination with ICI (Sintilimab) in patients with MSS oligometastatic colorectal cancers, to assess safety and tolerability of the regimen, and evaluate its early efficacy as well. ;

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

• NCT number: NCT04535024
• Study type: Interventional
• Source: Fudan University
• Contact: Zhen Zhang, MD, PhD
• Phone: 18801735029
• Email: zhen_zhang@fudan.edu.cn
• Status: Recruiting
• Phase: Phase 2
• Start date: March 4, 2021
• Completion date: December 2022