Determination of the number of tdEVs in plasma and urine in PCa patients at different stages, together with appropriate controls. This will be determined by the use of different EV enumeration and molecular techniques. For comparison, some sample…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter is the number of tdEVs, the ctDNA, and the unique mRNA
reads in plasma and urine from PCa patients, measured once without follow-up
for all participants except the prostatectomy patients where it will be
measured at most three times (confirmation of elevated PSA, before and after
prostatectomy).
Secondary outcome
-
Background summary
Prostate cancer (PCa) is the second most frequently diagnosed cancer and the
sixth cause of cancer-related death in men worldwide [1]. Prognosis and
monitoring of therapy efficacy in metastatic castrate resistant prostate cancer
(PCa) is possible using circulating tumor cells (CTCs) in whole blood [1-3]. In
castration resistant PCa patients (CRPC) the median concentration is 5 CTC*s/
7.5 mL whole blood [2]. This low number results in a large uncertainty on the
actual concentration of CTCs, which in turn limits the application of CTCs in
clinical practice. To detect more CTCs one would either require substantially
larger blood samples, or the adjustment of the CTC definition to also include
CTC derived particles [4]. A larger blood volume is undesirable due to the
burden for the patient. Large (2-4 µm) tumor derived extracellular vesicles
(tdEVs) are equally prognostic to CTC, with a 30-fold higher concentration [5].
This result is remarkable because these tdEVs were measured in the cell
fraction (red blood cell + buffy coat), while we expect to find the majority in
blood plasma. Furthermore, we also expect to find tdEVs in urine. At present,
the concentration of tdEVs in plasma and urine are unknown.
Furthermore, the presence of at least one CTC/30 mL blood was prognostic for
reduced survival in early stage breast and colorectal cancer [6, 7]. A low
number of CTC*s were found in locally advanced PCa patients, but not evaluated
for prognostic value [10]. Because the number of CTC*s correlates to disease
stage, and tdEVs are more numerous, we expect to find tdEVs in earlier stage
PCa patients, albeit at a lower concentration than in mCRPC patients. Thus, the
concentration of tdEVs might be a prognostic indicator for all stages of PCa.
A radical prostatectomy is expected to greatly reduce the number of tdEVs, and
thus is expected to prove that the detected tdEVs are prostate specific.
The composition of the selected population is aimed at a first determination of
the number of tdEVs in plasma and urine in PCa patients at different stages,
together with appropriate controls.
1. de Bono, J.S., et al., Circulating Tumor Cells Predict Survival Benefit from
Treatment in Metastatic Castration-Resistant Prostate Cancer. Clinical Cancer
Research, 2008. 14(19): p. 6302-6309.
2. Scher, H.I., et al., Circulating tumour cells as prognostic markers in
progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial
data. Lancet Oncology, 2009. 10(3): p. 233-239.
3. Coumans, F.A., S.T. Ligthart, and L.W. Terstappen, Interpretation of changes
in circulating tumor cell counts. Translational oncology, 2012. 5(6): p. 486.
4. Coumans, F.A., et al., Challenges in the Enumeration and Phenotyping of CTC.
Clinical Cancer Research, 2012.
5. Coumans, F.A.W., et al., All circulating EpCAM+CK+CD45- objects predict
overall survival in castration-resistant prostate cancer. Annals of Oncology,
2010. 21(9): p. 1851-1857.
6. Franken, B., et al., Circulating tumor cells, disease recurrence and
survival in newly diagnosed breast cancer. Breast Cancer Research, 2012. 14(5):
p. R133.
7. van Dalum, G., et al., Importance of circulating tumor cells in newly
diagnosed colorectal cancer. International Journal of Oncology, 2015. 46(3): p.
1361-1368.
8. Cristofanilli, M., et al., Circulating tumor cells, disease progression, and
survival in metastatic breast cancer. N Engl J Med, 2004. 351(8): p. 781-91.
9. Cohen, S.J., et al., Prognostic significance of circulating tumor cells in
patients with metastatic colorectal cancer. Annals of Oncology, 2009. 20(7): p.
1223-1229.
10. Thalgott, M., et al., Detection of circulating tumor cells in different
stages of prostate cancer. Journal of cancer research and clinical oncology,
2013. 139(5): p. 755-763.
Study objective
Determination of the number of tdEVs in plasma and urine in PCa patients at
different stages, together with appropriate controls. This will be determined
by the use of different EV enumeration and molecular techniques. For
comparison, some sample will be analysed for circulating tumor DNA (ctDNA). The
applied techniques include, but are not limited to, immunogold electron
microscopy, scanning electron microscopy, flow cytometry, (superresolution)
confocal microscopy, Raman microspectroscopy, long and short read mRNA
sequencing, PCR (with mutation specific probes).
Study design
This is a human, ex-vivo pilot study without follow-up.
Study burden and risks
The burden is limited to approximately 18 mL of blood, and 40 mL of urine.
Adverse events are not expected. Standard of care as stated by the AMC
protocols will not be affected by the choice regarding participation in this
study. The results of this study do not influence the clinical decision making
for the optimal treatment modality. There are no direct benefits for patients
participating in this study. The results of this study are important for future
patients. In conclusion, we believe that the burden and risk associated with
participation in this study are neglectable.
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
Healthy volunteers (N=10):
Adult male not related to the Urology department <= 40 years old.
Informed consent signed.;Elevated PSA level (N=40):
Patients presenting with a PSA level >= 3.0 ng/mL.
Informed consent signed.;Before/after prostatectomy (N=10):
Patients with localized PCa after prostate biopsy, who are planned for radical prostatectomy.
Informed consent signed.;mCRPC (N=10):
Patients with histologically confirmed prostate cancer that is metastatic and progressing despite castrate levels of testosterone (<50 ng/mL).
Informed consent signed.
Exclusion criteria
Healthy volunteers:
Clinical signs of prostate diseases, no medical or surgical therapy for prostate disease.;Elevated PSA level:
Patients with a history or presence of other cancers, or non-prostate urological disorders.;Before/after prostatectomy:
None. ;mCRPC:
None.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL64623.018.18 |
| OMON | NL-OMON28556 |