To validate promising circulating predictive biomarkers for FOLFIRINOX response in patients with PDAC, found in our previous pilot cohort (iKnowIT study, NL65025.078.18, MEC-2018-087) and to generate a biobank of blood samples to investigate future…
ID
Source
Brief title
Condition
- Exocrine pancreas conditions
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To validate the predictive value of circulating TP53 tumor mutations before
chemotherapy in combination with a homozygote TP53 Pro72arg germline variant
AND the predictive value of circulating microRNA 17-3p, 18a-5p, 194-5p, 24-3p,
and 27a-3p expression before and after one cycle of chemotherapy for the
prediction of progressive disease during FOLFIRINOX treatment in PDAC patients.
Secondary outcome
To collect blood samples of PDAC patients during chemotherapy treatment and
create a pancreatic biobank to investigate future predictive or prognostic
biomarkers. In addition, we will expand our biomarker research field with
fragmentomics for which we work together with the Amsterdam University Medical
Centre (Amsterdam UMC).
Finally, we will investigate the correlation between circulating biomarkers and
tissue IHC for molecular subtypes in pancreatic cancer.
Background summary
Pancreatic ductal adenocarcinoma (PDAC) has a very high mortality rate,
partially because of diagnosis at late stage of disease. Only 20% of patients
present with resectable disease. Nowadays, the standard first-line treatment
for locally advanced (LAPC) and metastatic PDAC is FOLFIRINOX chemotherapy, a
combination of fluorouracil, leucovorin, irinotecan and oxaliplatin. Despite
increased overall survival in FOLFIRINOX-treated patient groups, 20-30% of
patients will already show progressive disease during chemotherapy treatment.
In the meantime, 60-70% of patients experiences grade 3-5 toxicity from
FOLFIRINOX treatment. Biomarkers, especially those that can be easily measured
in the peripheral blood instead of tumor tissue, are necessary to stratify
patients for available therapies. Being able to select only patients that will
benefit from FOLFIRINOX chemotherapy could prevent non-responding patients from
severe FOLFIRINOX-induced toxicity. These non-responders might benefit from
other types of (chemo)therapy instead. In a previous pilot study
(NL65025.078.18, MEC-2018-087), we found some promising candidate biomarkers,
measured in the peripheral blood of PDAC patients, that might predict
FOLFIRINOX response. In addition, we will investigate the correlation of
circulating biomarkers with tissue immunohistochemistry (IHC) for molecular
subtypes of pancreatic cancers. These subtypes have previously been identified
and are known to correlate to prognosis, but are also expected to predict
response to FOFIRINOX. Correlating the IHC with the biomarkers could give more
insight into the disease and understanding of the prognosis and therapy
response.
Study objective
To validate promising circulating predictive biomarkers for FOLFIRINOX response
in patients with PDAC, found in our previous pilot cohort (iKnowIT study,
NL65025.078.18, MEC-2018-087) and to generate a biobank of blood samples to
investigate future biomarkers.
Study design
Prospective multicenter cohort study. 240 patients will be included over a
period of 2 years (200 in the experimental group and 40 in the control group).
Blood samples will be drawn at three time points: before the first cycle and
before the second cycle of FOLFIRINOX, and after 4 cycles of FOLFIRINOX. After
every 4 cycles of FOLFIRINOX a CT scan will be performed as standard of care to
evaluate progression of disease. Additionally, tissue obtained for diagnosis
will be investigated for correlation between immunohistochemical subtypes and
circulating biomarkers.
Study burden and risks
There is no extra benefit or risks for the patients involved.
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
's-Gravendijkwal 230
Rotterdam 3015 CE
NL
Listed location countries
Age
Inclusion criteria
Experimental group
• Age >= 18 years.
• Diagnosed with (borderline) resectable, locally advanced or metastatic PDAC.
• Treatment with FOLFIRINOX chemotherapy, including neoadjuvant therapy.
• Written informed consent (either for PANCAKE in case of locally advanced PDAC
and metastasized PDAC or for the PREOPANC-2/PREOPANC-3 trial in case of
(borderline) resectable PDAC).
Control group
• Age >= 18 years.
• Diagnosed with (borderline) resectable, locally advanced or metastatic PDAC.
• Treatment with gemcitabine, with or without nab-paclitaxel, chemotherapy,
including neoadjuvant therapy.
• Written informed consent (either for PANCAKE in case of locally advanced PDAC
and metastasized PDAC or for the PREOPANC-2 trial in case of (borderline)
resectable PDAC).
Exclusion criteria
Experimental group
• Combined treatment with other chemotherapeutics then FOLFIRINOX.
• Previous treatment with FOLFIRINOX chemotherapy.
• Pregnancy.
• Serious concomitant systemic disorders that would compromise the safety of
the patient or his/her ability to complete the study, at the discretion of the
investigator.
Control group
• Combined treatment with other chemotherapeutics then gemcitabine and
nab-paclitaxel.
• Previous treatment with FOLFIRINOX or gemcitabine-based chemotherapy.
• Pregnancy.
• Serious concomitant systemic disorders that would compromise the safety of
the patient or his/her ability to complete the study, at the discretion of the
investigator.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL75936.078.20 |