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The goal of this clinical study is to to improve diagnosis, follow-up and treatment for patients with disseminated prostate cancer.
The aim is to isolate tumour cells before image diagnostic methods find the metastases. In addition, investigators will use this method to characterise the tumour cells at the "single-cell" level to understand both the metastasis process, early resistance mechanisms and thus find new treatment targets to optimise individualised treatment.
Research subjects who either have disseminated disease at diagnosis or have recurrence after surgery (with minimal dissemination) will be included. A control population of young men without cancer will also be recruited to distinguish tumor-specific changes from normal signals using these new methods.
In this prospective clinical study, led by Umeå University, all research subjects will undergo apheresis and subjects with cancer will also undergo multiple radiological examinations to both identify apheresis and subsequent experimental protocols for isolation of tumor cells, immune cells and other components from the blood. The goal is to increase the sensitivity of identifying circulating tumor cells in early-stage metastatic prostate cancer for molecular characterization without biopsies of metastases. By doing this on multiple occasions in primary metastatic prostate cancer, investigators will identify early resistance mechanisms to given treatment and also investigate immune changes to standard treatment of metastatic prostate cancer (castration). Through qualitative approach, investigators will identify healthy and risk factors for managing the diagnosis of metastatic prostate cancer and the experience of undergoing apheresis to identify circulating tumor cells (CTC) in the blood, with the aim of identifying possible risks for mental health with this research.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Primary metastatic prostate cancer | Experimental | Men who have not previously received treatment for prostate cancer. |
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| PSA relapse | Experimental | Men with PSA recurrance after surgery. |
|
| Healthy research subjects | Other | Control group to distinguish tumor-specific changes from normal signals. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apheresis | Diagnostic Test | Isolate tumor cells, immune cells, exosomes and cell free DNA from the blood by a clinically used method of whole blood volume filtration, apheresis, and subsequent separation of blood components using novel techniques, such as acoustophoresis and other experimental protocols. |
| Measure | Description | Time Frame |
|---|---|---|
| Identify circulating tumor cells (CTC) for molecular characterization | Identification of circulating tumor cells will be accomplished by RNA-based phenotyping using lineage specific transcripts. | At inclusion in the study and after 4 weeks of treatment. |
| Differentiated gene expression in CTCs before and after treatment start | To find resistance mechanisms by deep molecular characterization of CTC before and after treatment start to identify up and down regulations of genes in paired samples. | At inclusion in the study and after 4 weeks of treatment. |
| Phenotypical changes of immune cells due to anti-androgen treatment | Broad molecular characterization of immune cells before initiation of treatment and at different time points after anti-androgen treatment | At inclusion in the study, after 4 weeks of treatment, after 3, 6 and 12 months of treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Progression free survival | Time to progression defined as PSA relapse or new metastasis or prostate cancer death, which ever comes first. | Within 24, 48 and 72 months respectively |
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Inclusion Criteria:
-The patient (arm 1 and arm 2) must have a health status that minimises the already low risks of the apheresis treatment, have the logistical possibilities to come to the visits according to the study and be planned for treatment according to standard treatment in Sweden today.
For arm 1, 2 and 3:
Additional inclusion criteria for Arm 1 - Metastatic prostate cancer
One of the following criteria:
Additional inclusion criteria for Arm 2 - PSA relapse after operation
All of the three following criteria must be fulfilled:
Additional inclusion criteria for Arm 3 - Healthy research subjects (control group)
All of the following two criteria must be fulfilled:
Exclusion Criteria for arm 1, 2 and 3:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andreas Josefsson, MD, PhD | Contact | +46 70 3805395 | andreas.josefsson@umu.se |
| Name | Affiliation | Role |
|---|---|---|
| Andreas Josefsson, MD, PhD | Department of surgical and perioperative sciences, Urology, Umeå University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of surgical and perioperative sciences, Umeå university | Recruiting | Umeå | Norrlands University Hospital | 90185 | Sweden |
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| ID | Term |
|---|---|
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D005834 | Genital Neoplasms, Male |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000726 | Androgen Antagonists |
| ID | Term |
|---|---|
| D006727 | Hormone Antagonists |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D045505 | Physiological Effects of Drugs |
| D020228 | Pharmacologic Actions |
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Three groups of research subjects
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| Androgen deprivation therapy | Other | Apheresis will be performed before initiation of systemic therapy (androgen deprivation therapy) and 4 weeks after. Androgen deprivation therapy is treatment as per clinical routine and not part of the protocol. |
|
| Anti androgen therapy | Diagnostic Test | Apheresis will be performed before initiation of systemic therapy (anti androgen therapy). Anti androgen therapy is treatment as per clinical routine and not part of the protocol. |
|
| D005832 |
| Genital Diseases, Male |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| D020164 | Chemical Actions and Uses |