Develop and evaluate the potential of TEPs and ctDNA as a novel liquid biomarker for early ovarium cancer diagnostics. And to evaluate the accuracy of ctNDA on response evaluation in patients with ovarian carcinoma.
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
To distinguish benign ovarium lesions from early cancer lesions, based upon
their ctDNA en platelet RNA profile.
To evaluate the accuracy of prediction response of ovarian carinomas on
therapy.
Secondary outcome
Evaluate the diagnostic accuracy of ctDNA and platelet RNA profiling in
detecting early-stage ovarium cancer compared to healthy controls;
Evaluate the diagnostic accuracy of ctDNA and platelet RNA profiling in
detecting early-stage ovarium cancer compared to stage IV ovarium cancer;
Evaluate the accuracy of ctDNA and platelet RNA profiling in differentiating
between ovarium cancer and other tumor types.
Background summary
Cancer is primarily diagnosed by clinical presentation, imaging and pathological
analysis of tissue biopsies, increasingly supported by molecular diagnostics
tests. However,
late diagnosis and misdiagnosis due to limitations of tissue biopsy acquisition
remains a major problem. Therefore, a general blood test to pinpoint cancer
early and adequately can be considered the *Holy Grail*, because diagnosis in
an earlier stage significantly improves the chance of cure from cancer. Several
blood-based biosources are currently being evaluated as liquid biopsies,
including cell-free DNA and circulating tumor cells, but none of these have
been implemented for primary (multiclass) cancer diagnostics. Tumor-educated
platelets (TEPs) can function as potential blood-based biosource for (early)
cancer diagnostics. Blood platelets - the second most-abundant cell type in our
blood - are implicated in hemostasis and wound healing. Platelets have recently
emerged as central players and immediate responders in the systemic and local
responses to tumor growth. Confrontation of platelets by tumor cells via
transfer of tumor-associated biomolecules (*education*) results in the
sequestration of these biomolecules (derived from both tumor and its
micro-environment), causing a distinct platelet mRNA profile. We have
previously shown that platelets acquire glioblastoma and prostate cancer mRNA
biomarkers and that glioblastoma TEP mRNA profiles harbour diagnostic potential.
A landmark paper in Science has recently shown that, by combining analysis of
ctDNA and protein tumor markers, depending on the tumor type, sensitivities of
between 50 and 100% (nearly 100% sensitivity for FIGS. 1 to III ovarian
carcinoma) are achieved. to show tumors, which can be treated curatively with
an operation. The specificity was at least 99% for each tumor type (Cohen et al
Science 2018).
The Catharina Kanker Institute (CKI) has already gained experience in the use
of liquid biopsy. A clinical study has been in progress for a year and a half
with patients suspected of lung cancer. In addition to the standard studies,
material for analysis of circulating tumor DNA (ctDNA) and protein tumor
markers is taken from these patients. For the analysis of ctDNA is recent, d.m.
an external subsidy, a PCR device suitable for the sensitive detection of ctDNA
in plasma. A first spin-off of this scientific research will be introduced in
routine diagnostics around the summer
This amendment request relates to the addition of protein tumor markers and of
circulating DNA as a liquid diagnostic to the TEP study. For this purpose, an 8
ml EDTA and 4 ml solid blood should be taken from this test subject population,
in addition to the 4 ml EDTA tube.
analysis
With the material obtained prospectively the clinical value of ctDNA analysis
and protein tumor markers will be determined when diagnosing ovarian carcinoma,
differentiation and treatment of this and monitoring the course of the therapy.
Study objective
Develop and evaluate the potential of TEPs and ctDNA as a novel liquid
biomarker for early ovarium cancer diagnostics. And to evaluate the accuracy of
ctNDA on response evaluation in patients with ovarian carcinoma.
Study design
Multicenter, Investigator-initiated, observational study
Study burden and risks
There is no extra burden/risk for the patients in this study. There will
collect 1-3 x 3 veils of blood during a clinical blood withdrawal.
Michelangelolaan 2
Eindhoven 5623 EJ
NL
Michelangelolaan 2
Eindhoven 5623 EJ
NL
Listed location countries
Age
Inclusion criteria
Patients who are suspected of having ovarian cancer, patients who are diagnosed
with ovarian cancer, and patients with ovarian cysts of which it is unknown
whether it is benign or malignant and who receive either surgery with
definitive pathology or follow up.
Exclusion criteria
Woman diagnosed with any type of cancer besides ovarian cancer.
Previous intra-abdominal malignancies in the history
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 | NL68037.100.18 |