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JOURNAL ONKOLOGIE – STUDIE
FLUIDO

Circulating Tumor DNA as Marker for Response to Antineoplastic Treatment of Metastatic Cancer (FLUIDO)

Rekrutierend

NCT-Nummer:
NCT04793061

Studienbeginn:
April 2021

Letztes Update:
11.03.2021

Wirkstoff:
-

Indikation (Clinical Trials):
Neoplasm Metastasis, Neoplasms, Neoplasms, Second Primary

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
-

Sponsor:
Elisabethinen Hospital

Collaborator:
Medical University Innsbruck

Studienlocations
(1 von 1)

Studien-Informationen

Detailed 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.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Metastatic cancer (mPDAC, mGC, mCRC)

- Known mutation of the cancer

- Signed informed consent

- At least 18 years

- Eligible for antineoplastic treatment

Exclusion Criteria:

o Inclusion criteria not met

Studien-Rationale

Primary outcome:

1. ctDNA dynamics correlate with response to antineoplastic treatment (Time Frame - 3 months per patient):
ctDNA concentration in peripheral blood will drop if patient respond to treatment

Geprüfte Regime

  • blood sample collection:
    Blood is samples from peripheral vein during routine care

Quelle: ClinicalTrials.gov


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