NCT03808441

CAcTUS - Circulating Tumour DNA Guided Switch

A Parallel Arm, Biomarker Driven, Phase II Trial to Determine the Role of Circulating Tumour DNA in Guiding a Switch Between Targeted Therapy and Immune Therapy in Patients With Advanced Cutaneous Melanoma

• Status: Unknown
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 21 (actual)
• Sponsor: The Christie NHS Foundation Trust · Academic / Other
• Sex: All
• Age: 16 Years
• Healthy volunteers: Not accepted

Summary

The stay aims to determine whether switching from targeted therapy to immunotherapy based on a decrease in levels of circulating tumour DNA in the blood, will improve the outcome in melanoma patients.

Detailed description

The optimal scheduling of targeted and immune therapies in metastatic melanoma is unknown. At present, patients are treated with targeted therapy until acquired resistance develops, and then switched to immune therapy. Pre-clinical data has revealed that BRAF inhibition results in an environment that can enhance immune responses. Tumours responding to BRAF inhibitors but not resistant have been shown to have increased T cell infiltration, improved T cell recognition of melanoma associated antigens and reduced production of immunosuppressive cytokines. Furthermore, in response to targeted therapy LDH levels, which are associated with decreased response to immune therapy reduces, which may improve efficacy of immunotherapy. A precise definition of response is required in order to decide upon a switch to immune therapy. A radiological definition of response is currently the standard assessment. However a scan at a fixed time point of 2 or 3 months does not reflect the wide range of response dynamics or allow decision making on an individual patient basis. The investigators have developed techniques using circulating tumour DNA (ctDNA) in the metastatic setting, which are able to accurately monitor tumour burden over time. The aim of this pilot study is to provide a signal as to whether: 1. In BRAF mutant melanoma the efficacy of immune therapy is enhanced by response to pre-treatment with MAPK pathway inhibition with dabrafenib + trametinib. 2. Changes in ctDNA levels can be used to accurately inform when to switch from targeted to immune therapy. Data from this study will provide the basis for follow on studies with sufficient power to assess whether tumours responding to BRAF inhibition as defined by response in ctDNA can improve efficacy of immune therapy.

Conditions

• Melanoma

Interventions

Type	Name	Description
OTHER	ctDNA analysis	Regular ctDNA analysis, which upon a decrease in mutant BRAF VAF (variant allele frequency) level of ≥80% the switch to N+I is triggered.

Timeline

• Start date: 2019-05-02
• Primary completion: 2023-04-26
• Completion: 2024-05-02
• First posted: 2019-01-17
• Last updated: 2023-08-25

Locations

1 site across 1 country: United Kingdom