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Avelumab Plus 5-FU Based Chemotherapy as Adjuvant Treatment for Stage 3 MSI-High or POLE Mutant Colon Cancer

NCT03827044 · Status: TERMINATED · Phase: PHASE3 · Type: INTERVENTIONAL · Enrollment: 30

Last updated 2022-10-07

No results posted yet for this study

Summary

The purpose of this study is to determine if dMMR and/or POLE exonuclease domain mutant stage III colon cancer patients gain clinical benefit (i.e. improvement in disease free and overall survival) from PD-L1 inhibitors after standard fluoropyrimidine-based adjuvant chemotherapy.

Avelumab binds PD-L1 and blocks the interaction between PD-L1 and PD-1. This removes the suppressive effects of PD-L1 on anti-tumour CD8+ T cells, resulting in the restoration of cytotoxic T cell response.

The rationale of giving Avelumab after standard adjuvant chemotherapy to this well-defined, molecularly-selected, group is based on the fact that dMMR and POLE exonuclease domain mutant CRCs have a highly and ultra-mutated genetic profile, respectively, thus leading to a high number of neo-antigens with associated over expression of immune checkpoint related proteins. This profile is expected to be highly responsive to checkpoint inhibition as suggested by data of PD-1 inhibitors in dMMR/MSI-H metastatic CRCs.

If this study meets the primary endpoint, using Avelumab in the adjuvant setting following standard chemotherapy would become the standard of care for patients with dMMR and/or POLE exonuclease domain mutant colon cancers. Furthermore, given the availability of molecular markers for patient selection, funders of healthcare would be more likely to fund this treatment.

This study also provides a unique opportunity to conduct translational research analyses on pre- and post-treatment tumour tissue samples and blood samples from dMMR or POLE mutant CRC patients treated with the checkpoint inhibitor Avelumab.

Conditions

  • POLE Exonuclease Mutant Colon Cancer
  • Microsatellite Instability
  • Stage III Colon Cancer

Interventions

DRUG

Avelumab

Avelumab is a fully human monoclonal antibody (MoAb) of the immunoglobulin G (IgG) 1 subtype which specifically binds to the PD-L1 cell surface ligand and blocks its interaction with the PD-1 cell surface receptor.

Sponsors & Collaborators

  • University of Surrey

    collaborator OTHER

  • University of Oxford

    collaborator OTHER

  • Merck KGaA, Darmstadt, Germany

    collaborator INDUSTRY

  • Royal Marsden NHS Foundation Trust

    lead OTHER

Principal Investigators

  • Tony Dhillon, Bsc,FRCP, PhD · University of Surrey

Study Design

Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
PARALLEL

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2018-08-31
Primary Completion
2021-01-05
Completion
2022-01-05
FDA Drug
Yes

Countries

  • United Kingdom

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT03827044 on ClinicalTrials.gov