Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04793061 |
| Other study ID # |
FLUIDO-001 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 1, 2021 |
| Est. completion date |
November 30, 2022 |
Study information
| Verified date |
March 2021 |
| Source |
Elisabethinen Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
Early monitoring of antineoplastic treatment benefit is a central medical need. Radiologic
assessment for documentation of response is done after several months of treatment usually.
This implies that patients not responding are exposed to unnecessary toxicity. According to
several reports showing the correlation of the amount of circulating tumour DNA with tumour
burden we aim to investigate its early dynamic change at the beginning and during
antineoplastic treament until radiologic response assessment. Blood samples necessary for
that are taken within the scope of clinical routine care. We hypothesize that the changes of
circulating tumour DNA correlate with the radiological findings.
Description:
Patients Patients with metastatic cancer who are treated with antineoplastic treatment are
eligible if a molecular marker is either known due to the type of cancer (Case A) or if a
molecular marker is known due to routine assessment (Case B). An example for "Case A" is
pancreatic cancer, which is known to harbor KRAS-mutations as part of tumorigenesis in more
than 90% (8), or multiple cancers harboring methylated WIF(9). A typical example for "Case B"
is colorectal or gastric cancer. Systemic treatment requires the knowledge of the mutational
status of RAS, EGFR and BRAF, which is assessed routinely from tumor tissue. If a mutation is
found the patient qualifies for participation in the project. We finally plan to include at
least 40 patients with mPDAC, another 40 patients with mCRC and 20 patients with mGC (100
patients in total at least).
- The inclusion criteria therefore are:
- Metastatic cancer (mPDAC, mGC, mCRC)
- Known mutation of the cancer
- Signed informed consent
- At least 18 years
- Eligible for antineoplastic treatment
- Patient treated at the Ordensklinikum Linz
- Exclusion criteria o Inclusion criteria not met
Treatment monitoring Circulating tumor DNA is analysed from peripheral blood. For this
purpose, 30 ml blood is taken at start and during treatment additionally to the blood volume
required for analyses in the frame of routine. Therefore, there are no extra blood sampling
time points additionally to these required for routine care. Due to that, the time points
depend on the cancer type investigated as treatment schedules are different. However, within
an entity the time points are homogenous.
Analysis of ctDNA The preparation of ctDNA is done in the Laboratory for Molecular Biology
and Tumor Cytogenetics at the Ordensklinikum Linz (Dr. Gerald Webersinke) and digital droplet
PCR is performed by the Department of Genetics at the Medical University of Innsbruck (Prof.
Johannes Zschoke). The analysis is performed in a batch and not in real time. In detail,
ctDNA detection is based on KRAS-screening in mPDAC or by patient specific ddPCR. The latter
patient specific ddPCR is based on the mutations found in the tumor by NGS-screening (ARCHER
or Truesight 170 or whole-genome sequencing if panels are negative) at the Laboratory in
Linz. This is the case for mGC and mCRC, where multiple mutations are possible (KRAS, NRAS,
BRAF, TP53). In patients suffering from mCRC, this analysis in performed within routine
procedures as such mutations are crucial for treatment decisions. In case of mGC mutations
screening is done within the proposed project.
Radiology assessment Assessment of treatment response is performed as part of the routine
treatment after two to three months of treatment at the department of Radiology of the
Ordensklinikum Linz.
Statistics Data are analyzed in order to detect a dependency between ctDNA dynamics and
response to treatment. Method for example is chi-square test. Software used is RStudio
Version 1.2.5019.
Descriptive Statistics Mean, standard deviation, minimum and maximum for every concentration
of ctDNA at each time point.
ROC-AUC analysis for every time point
- Dynamics of ctDNA concentration at every time point (metric variable)
- Outcome after 12 weeks as a dichotome variable (responder [SD/PR/CR], non-responder)
- Calculation of AUC with 95% CI (all time points)
- ROC-curve (all time points)
- Calculation of sensitivity and specificity for all time points with 95% CI
- Determination of the optimal threshold-value upon sensitivity and specificity for every
time point
- Comparison of predictive value of each time point based on sensitivity/specificity, AUC
by CI-values
Power-analysis Based on the current patient recruitment we assume to end up with a final
number of 100 patients.
Assumptions:
- n = 100
- Power 80 %
- Significance-niveau 5 %, Confidence-Intervall (CI) 95 %
- Proportion of responders (estimated prevalence): 0.2, 0.4 and 0.6
- Sensitivity and specificity: 0.6, 0.7 and 0.8
- Dropout-rate: 15 %
Plan for analysis We first compare Roc curves at the different timepoints to identify the
timepoint that as the best tradeoff between performance and gain of time (lack of power to
provide statistical comparisons). In a second step, we identify the best cut point of ctDNA
at the chosen timepoint based on youden index for instance and give sensitivity/specitivity
and also NPV/PPV at this cut-point.
