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

Patients with a gastrointestinal stromal cell tumor (GIST) are mostly treated
long-term with anti-cancer drugs. Currently, a CT-scan is made every 3-12
months to monitor the response to therapy, according to the guidelines of the
Dutch GIST consortium. CT-scans are relatively expensive and can expose
patients to accumulative high levels of radiation. In case of progressive
disease, a biopsy is taken to investigate secondary mutations. This is an
invasive method. An alternative to monitor response could be assessment of
circulating tumor DNA in blood. In a previous study we have developed an assay
to detect and quantify the most common GIST mutations in KIT exon 11. Adding an
extra tube for assessment of ctDNA to the regular blood draws during follow-up,
could provide a solid and non-invasive follow-up strategy.

To establish the negative predictive value of the designed KIT exon 11
circulating tumor mutation assay in relation to CT-scans (and/or MRI scans).

An observational, multicenter study will be performed. Regular 3-12 monthly
follow-up by CT-scan will be compared to results of ctDNA analysis. CtDNA
results will be assessed at the same moment a CT-scan is performed.
Additionally, in case of initiation of a new therapy an extra ccfDNA sample
will be collected within 1-2 weeks after start therapy. All samples will be
analyzed at the reference Pathology laboratory at the UMCG. A part of the
samples will also be analyzed in other institutions to implement the ddPCR.
Primary endpoint is concordance between CT-scan (and/or MRI scan) and ctDNA
analysis results, from which the negative predictive value (NPV) of our ddPCR
assay will be calculated.

The only potential risk of ctDNA analysis is damage due the blood withdrawal,
which is considered very low (a small risk of pain, bruises or
thrombophlebitis). In our study, the vena puncture will be mostly performed at
the same moment standard laboratory tests are taken. Therefore, the risk and
burden is minimized.
Benefits of the assay could be substantial. Radiation load is reduced once
ctDNA can replace (some) CT-scans. Patients could experience ctDNA analysis as
less invasive than a scan (just one extra tube of blood during regular blood
draw). The most important benefit would however be if ctDNA analysis could
predict (developing) progression earlier than CT-scans (and/or MRI scans) by
the detection of secondary mutations, whereby earlier treatment adaptions could
be made based on the assessed secondary mutations.