No registrations found.
ID
Source
Brief title
Health condition
Prostate cancer, Metastatic hormone sensitive prostate cancer, mHSPC
Sponsors and support
Intervention
Outcome measures
Primary outcome
The percentage of patients from who 30 single viable CTCs can be isolated from the DLA product.
Secondary outcome
- 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(19) 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:
- 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 number of treatment options for patients with high-risk metastatic Hormone Sensitive Prostate Cancer (mHSPC) are rapidly expanding. Both chemotherapy and intensified anti-hormonal treatments deliver a significant improvement in overall survival. However, we are currently unable to predict which therapies are most effective in individual patients and the scarce randomized trial data comparing the 2 modalities fail to identify a clear preference. Thus, developing predictive biomarkers may provide an improved scientific basis to further improve the treatment of mHSPC patients. We will study a novel single cell phenotyping platform that enables the “ex vivo” testing of heterogeneity in drug responsiveness on individual tumor cells. We aim to correlate the results of the “ex vivo” single cell drug responsiveness testing to the clinical outcome in patients and to generate hypotheses on how and whether this novel technology could help to stratify patients with mHSPC for treatment allocation.
Study objective
We hypothesize that an improved understanding of the cellular heterogeneity, both between patients and within a single patient, will aid in developing improved individualized treatment strategies.
Study design
- Baseline: -28 days till -1 day
- DLA
- After 6 months of treatment
- At progression of disease
- Death
Intervention
From all patients, blood will be drawn to screen for eligibility, including a CellSave tube for circulating tumorcells count and circulating tumor DNA, tubes for liver, renal and bone marrow function. If eligible, patients will undergo a diagnostic leukapheresis (DLA) procedure.
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
IPD sharing statement
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 |
|---|---|
| NTR-new | NL8549 |
| Other | METC Erasmus MC : MEC-2020-0422 / NL73860.078.20 |