Primary objective: 1. To establish whether obtaining CTCs of mHSPC patients by DLA for single cell genotyping and phenotyping warrants further clinical exploration. Secondary objectives: 1. To investigate the number of CTCs in peripheral blood of…
ID
Source
Brief title
Condition
- Reproductive and genitourinary neoplasms gender unspecified NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint of this study is:
- The percentage of patients from who 30 single viable CTCs can be isolated
from the DLA product.
Secondary outcome
Secondary endpoints of this study are:
- The number of CTC in mHSPC patients obtained in peripheral blood and obtained
by DLA
- The correlation between the number of CTC at baseline and after six months of
treatment (defined as 6 months from start treatment for mHSPC) to clinical
outcome (defined as time to start mCRPC treatment, time to first line therapy
for CRPC, time to mCPRC as defined by PCWG3 and overall survival)
- The level of PSA secretion and cell stress factors on single CTCs after drug
exposure
- The percentage of patients from whom chromosomal profiles of single CTCs can
be successfully generated
- The levels of ctDNA in mHSPC patients obtained in peripheral blood at
baseline and after six months.
Exploratory endpoints of this study are:
- The intra-patient and inter-patient heterogeneity in genotype and phenotype
of single CTCs
- The correlation between genotypic and phenotypic characterization of single
CTCs
- The correlation between genomic heterogeneity and phenotypic heterogeneity of
individual cancer cells in poor and well responding mHSPC patients.
Background summary
The treatment of de novo mHSPC has evolved rapidly in the last years. After the
identification of a robust
survival benefit for 6 cycles of docetaxel added to Androgen Deprivation
Therapy (ADT) we now know
that the androgen receptor targeting drugs: abiraterone/ prednisone and
enzalutamide render robust
survival gains if started immediately concomitantly with ADT. The median
progression free survival of
these patients is estimated between 18 and 24 months, a major improvement,
which also poses a
number of challenges. First of all, we still see patients that recur relatively
quickly after therapy
initiation. These patients are difficult to identify upfront, so here we
urgently need a real predictive
biomarker.
Study objective
Primary objective:
1. To establish whether obtaining CTCs of mHSPC patients by DLA for single cell
genotyping and phenotyping warrants further clinical exploration.
Secondary objectives:
1. To investigate the number of CTCs in peripheral blood of mHSPC patients.
2. To investigate the number of CTCs obtained by DLA in mHSPC patients.
3. To correlate CTC count at baseline and after six months of therapy to
clinical outcome.
4. To develop a protocol enabling the isolation and identification of viable
CTCs in DLA
products of mHSPC patients.
5. To measure the excretion of PSA and cell stress factors on single CTCs with
or without exposure to drugs.
6. To generate DNA copy number profiles of single CTCs in mHSPC patients.
7. To investigate the levels of ctDNA in mHSPC patients
Exploratory objective:
1. To identify mHSPC patients that respond poorly and those that respond well
by combined phenotyping and genotyping of individual cancer cells.
Study design
This is a prospective, exploratory, multi center cohort study
Study burden and risks
The patients included in this study will undergo a DLA procedure which will
take a maximum of a couple of hours. A maximum volume of 5L peripheral blood
will be processed with the use of an Optia Spectra Cell Separator. This study
will not benefit the patients included. The most common adverse events which
could be expected are pain or bruising at the site of venipuncture (1-5%),
apprehension or fainting associated with venipuncture (1-5%), fluid imbalance
(0.01-0.1%) and citrate anticoagulant infusion-related symptoms resulting in
tingling or buzzing around the mouth or fingers (20-50%). All patients will
receive intravenous calcium to prevent this. The risks associated with
participation are considered negligible. All safety measures and procedures
will be performed according to local guidelines.
Participation in this study requires additional blood draw, the total needed
blood volume varies, but has a maximum of 70ml. The risk of this limited amount
of blood being drawn is minimal. The risks are considered negligible.
dr. Molewaterplein 40
Rotterdam 3015GD
NL
dr. Molewaterplein 40
Rotterdam 3015GD
NL
Listed location countries
Age
Inclusion criteria
- De novo mHSPC patient, no prior treatment for prostate cancer, including
local treatments and ADT
- Intention to start treatment with ADT + docetaxel or ADT + Second Generation
Androgen Receptor Targeted therapy
- Age >=18 years
- WHO performance status <=2.
- >= 2 adequate peripheral veins as access point for leukapheresis.
Exclusion criteria
- Known hypersensitivity to the anticoagulant used for apheresis
- Inadequate cardiac function or severe cardiovascular comorbidity
* Heart failure NYHA class III/IV
- Hemoglobin level < 6.0 mmol/L
- Coagulation disorders as defined by one of the following:
* Coagulation disorder in medical history
* Platelet count < 40 x 109/L;
Patients without anticoagulant therapy which affects PT
or APTT, when:
* PT > 1.5 x ULN or PT-INR > 1.5 x ULN
* APTT > 1.5 x ULN
Patients with anticoagulant therapy which affects PT or APTT, when:
* PT or APTT > 1.5 x the upper limit of the desired therapeutic window
* Total bilirubin > 2.5 x ULN
- Known chronic viral infections
- Second active malignancy
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 | NL73860.078.20 |