OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer -

Study Overview
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Brief Summary
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The present study will investigate the feasibility and clinical value of using circulating tumor DNA as selection for anti-epidermal growth factor receptor treatment for metastatic colorectal cancer.

Detailed Description
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The primary aim of this prospective study is to investigate if cfDNA in plasma is feasible and reliable for selection of mCRC patients who will benefit of anti-EGFR monoclonal antibody therapy Secondary, to analyze developments in mutational status as reflected by cfDNA in plasma during therapy and at time of progression

Official Title
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OPTImal PALliative Anti-epidermal Growth Factor Receptor Treatment in Metastatic Colorectal Cancer - Feasibility Study Investigating Circulating Tumor DNA for Treatment Decisions

Conditions
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Colorectal Cancer Metastatic, Circulating Tumor DNA, KRAS Gene Mutation, NRAS Gene Mutation, BRAF Gene Mutation, Epidermal Growth Factor Receptor Inhibitor

Intervention / Treatment
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* Other: Plasma circulating DNA analysis


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Histopathologically verified metastatic colorectal cancer Indication for systemic palliative treatment with standard Anti-EGFR monoclonal antibodies Fit for therapy with EGFR inhibition Consent to treatment and sampling Measureable disease according to RECIST v 1.1 Age ≥ 18 Exclusion criteria PS > 2 Significant other cancer disease within 5 years of inclusion Conditions precluding sampling during therapy and treatment breaks.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Colorectal cancer patients<br>Clinical utility of ctDNA analysis for treatment decision Use of ctDNA for KRAS, NRAS and BRAF testing prior to potential anti-EGFR monoclonal antibody treatment for metastatic colorectal cancer | Other: Plasma circulating DNA analysis<br>* Clinical utility of ctDNA analysis for treatment decision<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of ctDNA analysis for RAS mutation analysis | Feasibility measures Identification of wildtype or mutated status and results delivered to clinicians Initial clinical test results i.e. ctDNA mutations or wildtype status within 7 days Detailed mutation type characterization is provided retrospectively. Failure parameters Quality of samples; PB > 5%, CPP1 major loss < 10% Transportation > 3 week days Analysis > 3 working days Total results delivered > 7 days. | maximum 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retrospective concordance analysis | Retrospective comparison of tumor mutation and plasma mutation analysis at baseline | By end of study, expected after 3 years | 
| Disease control rate | Rate of disease control | 1 year | 
| OS | Overall survival rate | 3 years | 
| Resistance mutations | Rate of Ectoderm mutations at time of progression | At time of progression, data analysis expected after 3 years | 
| Lead time | Calcualted lead time between radiologically detected progression and molecular biologically detected ( by Ectoderm and other resistance mutations) in the ctDNA. | At time of progression, data analysis expected after 3 years |