Validation of Mutation Analysis in Circulating Tumor DNA With a ddPCR Assay as Diagnostic and Follow-up Tool for Patients With a KIT Exon 11 Mutated GIST: GALLOP-11

Dutch Title

Onderzoek naar de optimalisering van de behandeling van Gastro-Intestinale Stroma tumoren (GIST) door het monitoren van mutaties in circulerend tumor DNA (ctDNA): GALLOP-11 studie

Acronym

GALLOP-11

Reference code

NCT05178030

Intervention model

Prospective observational cohort study

Full description

This is an observational, non-interventional, multicenter study. The study will be performed within the Dutch GIST consortium (NKI-AvL, Erasmus MC, Radboud UMC, LUMC and UMCG). Patients diagnosed with GIST with a KIT exon 11 mutations that can be detected by our ddPCR assay are eligible. In this way we will study a homogenous patient population with GIST that (usually) responds very well to initial TKI treatment. Therefore, the KIT mutation status must be known. Patients can enter the study at any time point of their disease trajectory. Patients included in GALLOP-11 will have follow-up as described in the European Society of Medical Oncology and Dutch guidelines but with blood draws for ctDNA assessment at similar time points.

The primary objective is the negative predictive value (NPV) of the ddPCR assay result in relation to the results of the CT-scan and/or MRI scan (according to RECIST 1.1) at the same time point. Concordance of these results will be determined, from which the negative predictive value (NPV) of our ddPCR assay will be calculated. This is considered the most important value, as the most harmful scenario would be to miss progressive disease because not seen on ctDNA while it could have been seen on CT (and/or MRI). That would mean that ctDNA analysis is not reliable enough to replace CT-scan (and/or MRI) follow-up in the future.

To determine the negative predictive value, at least 250 patients need to have an evaluable follow-up strategy. To pursue a solid follow-up period within an achievable timeline, patients with at least four ctDNA measurements, accompanied by a CT-scan (and/or MRI scan), will be considered evaluable for the NPV analysis. Patients who have progression within four scans are always evaluable, since a positive outcome outweighs negative outcomes because it is known that ctDNA should have had measured change once it is seen on CT-scans (and/or MRI scans).

Inclusion criteria

1. Patients with GIST with a biopsy confirmed primary KIT exon 11 mutation covered by our KIT exon 11 ddPCR assay (mutation/deletion within target sequence of c.1665_1736);
2. Patients with an indication for at least 4 CT-scans concomitant with regular laboratory examination in a neoadjuvant, adjuvant and/or palliative care trajectory within the time frame of the study;
3. Age ≥18 years;
4. Written informed consent provided

Exclusion criteria

1.  Patients who are unable to comply with study procedures and follow up

Locations

Netherlands Cancer Institute
Amsterdam, Netherlands
Contact: N. Steeghs, MD, PhD
Principal Investigator: N. Steeghs, MD, PhD

University Medical Center Groningen
Groningen, Netherlands
Contact: A. K.L. Reyners, MD, PhD +31 50 361 6161 a.k.l.reyners@umcg.nl
Contact: R. Bleckman, MD +31 50 361 6161
Principal Investigator: A. K.L. Reyners, MD, PhD

LUMC
Leiden, Netherlands
Contact: A. J Gelderblom, MD, PhD
Principal Investigator: A J Gelderblom, MD, PhD

Radboud UMC
Nijmegen, Netherlands
Contact: I. Desar, MD, PhD
Principal Investigator: I. Desar, MD, PhD

Erasmus MC
Rotterdam, Netherlands
Contact: R HJ Mathijssen, MD, PhD
Principal Investigator: R HJ Mathijssen, MD, PhD

Contact

A. K.L. Reyners, MD, PhD +31 50 361 6161 a.k.l.reyners@umcg.nl
R.F Bleckman, MD +31 50 361 6161 r.f.bleckman@umcg.nl