Clinical Utility of Selected Circulating Tumor DNA Assays in Patients With Advanced Malignancy

Recruiting

• Conditions: Cholangiocarcinoma; Metastatic Colorectal Cancer; Pancreas Adenocarcinoma
• Interventions: Diagnostic Test: Multiplex PCR-test for circulating tumor DNA

• Registration Number: NCT06290856
• Lead Sponsor: Oslo University Hospital

Brief Summary

Circulating tumor DNA assays are becoming relevant for routine diagnostics, but many related aspects are yet unresolved. With this project, the investigators aim to develop pragmatic molecular diagnostic pathways of liquid biopsies relevant in advanced gastrointestinal malignancies with focus on clinical utility and sensible use of resources. They want to evaluate the ctDNA assays on a fully automated "low-cost" multiplex platform which is already implemented in routine molecular diagnostics of solid biopsies. The project will evaluate to what extent these ctDNA assays are relevant for clinical decision-making.

Detailed Description

Advanced pancreatic cancer (PDAC) and cholangiocarcinoma (CCA): -Could the Idylla ctKRAS test select the \~10% of PDAC patients with KRASwt eligible for more extensive diagnostics? In PDAC and CCA, is it possible to detect patient samples with KRAS G12C or BRAF mutation for study inclusion? Could the ΔCq-value of the tests be used as a semi-quantitative tumor marker? What is the clinical value compared to the current tumor marker CA19-9?

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Metastatic Colorectal Cancer: Are the ctDNA assays useful in detecting primary resistance and/or monitoring for secondary/acquired resistance to EGFR antibody treatment? How does the sensitivity, specificity and turnaround time of the ctDNA assays compare to tissue-based analysis? Could the Idylla ctDNA assays accelerate detection of KRAS G12C or BRAF mutations, and hence facilitate study inclusion in the first line setting? Could the ctDNA assays guide rechallenge with EGFR treatment?

Can the information of liver metastases or prognostic markers (s-CEA, s-CRP) guide timing of ctDNA sampling?

Study Timeline

• Study Start: 2024-01-15
• Study First Submitted: 2024-02-26
• Study First Submitted QC: 2024-02-26
• Status Verified: 2024-03
• Study First Posted: 2024-03-04
• Last Update Submitted: 2024-03-05
• Last Update Posted: 2024-03-07
• Primary Completion: 2025-12-15
• Study Completion: 2025-12-15

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Newly referred patients with advanced pancreatic cancer (~20/year), Cholangiocarcinoma (~20/year), metastatic colorectal cancer (mCRC) (~50/year) and anti-EGFR-treated mCRC patients (~10/year) to Oslo University Hospital are eligible for inclusion.

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Advanced gastrointestinal malignancy	Multiplex PCR-test for circulating tumor DNA	Pancreatic cancer, Colorectal cancer, Cholangiocarcinoma

Primary Outcome Measures

Name	Time	Method
Clinical validity of ctDNA tests	1 week	Number of participants where the ctDNA results leads to changes in diagnostic work-up, treatment initiation or change of treatment.

Secondary Outcome Measures

Name	Time	Method
Resources needed for ctDNA assays in routine diagnostics	1 week	Ratio of certain clinical features (i.e. location of metastasis; liver versus lung) or biochemical markers (elevated CRP, CEA etc versus normal markers) that is associated with a positive ctDNA result. The rationale is that ctDNA usually is higher with liver metastases compared to lung and that elevated biochemical markers are associated with more progressive disease and hence more inclined to give positive ctDNA results. Cost efficient use relies on positive ctDNA results as the opposite result is non-informative.

Trial Locations

Locations (1)

Oslo university Hospital; 🇳🇴 Oslo, Norway