The primary objective of this study is to assess the rate of mPC patients with quantifiable individualized SVs in ctDNA from plasma taken pre-treatment. Secondary objectives include SV characterization in tumor biopsies, exploration of the…
ID
Source
Brief title
Condition
- Renal and urinary tract neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the rate of mPC patients with quantifiable
tumor-specific SVs in ctDNA from plasma taken pre-treatment; quantifiable is:
the number of SV copies per milliliter plasma (load) is above the lower limit
of detection (LLD).
Secondary outcome
Secondary, exploratory endpoints include the overlap in SVs between tumor
biopsy samples pre- and post-treatment, the longitudinal assessment of SV load
under influence of systemic treatment and the interval between detected
variations in SV load PSA response and imaging modality markers.
Background summary
Prostate cancer (PC) is the most common malignancy in men worldwide. At
diagnosis approximately 17% displays initial metastasized disease and an
additional 20-40% of PC patients will have metastatic disease (mPC) within 10
years after primary curative treatment. Several treatment modalities are
available to prolong progression free and overall survival, however it has
proven to be ambiguous to accurately monitor treatment response with the
current available response markers like prostate specific antigen (PSA) and
radiological imaging. With the discovery of circulating tumor DNA (ctDNA) a new
approach to non-invasively and safely obtain tumor-derived DNA has become
available. To use ctDNA as a highly sensitive and specific marker for early
therapy response we aim to detect and quantify somatic structural variants
(SVs) in ctDNA from mPC patients. SVs are widespread in cancer and comprise
small and large aberrations in genome structure. In PC predominant alterations
in involved signaling pathways are often caused by SVs. We hypothesize that the
load of circulating SVs is correlated with the metastatic prostate tumor load.
If so, variations in the concentration of tumor-specific SVs can potentially
serve as a new marker for measuring early therapy response and for detecting
minimal residual disease. If we can improve treatment response monitoring,
especially in the early phase, we will be able to advise patients promptly and
more precisely on the following treatment.
Study objective
The primary objective of this study is to assess the rate of mPC patients with
quantifiable individualized SVs in ctDNA from plasma taken pre-treatment.
Secondary objectives include SV characterization in tumor biopsies, exploration
of the concordance between SVs in ctDNA and tumor biopsies and the
investigation whether SV load in ctDNA correlates with tumor load and can
predict early treatment response.
Study design: Prospective, longitudinal, observational study.
Study design
Prospective, longitudinal, observational study.
Study burden and risks
Of all patients every 3 to 4 weeks 2x 10 ml blood will be drawn up to disease
progression occurs. As part of the CPCT-02 protocol a pre-treatment biopsy of a
metastatic lesion and/or locally advanced tumor site and an optional biopsy
after disease progression will be performed. Treatment response and disease
progression will be assessed according to current clinical guidelines. The risk
of longitudinal blood collections by venipuncture is negligible.
Wytemaweg 80
ROTTERDAM 3015 CN
NL
Wytemaweg 80
ROTTERDAM 3015 CN
NL
Listed location countries
Age
Inclusion criteria
- metastasized castration resistant prostate cancer
- participation in CPCT-02 study
- age * 18 years
- written informed consent
Exclusion criteria
- not meeting the inclusion criteria
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 | NL56192.078.16 |