APACA-Apheresis/acoustophoresis and Molecular Characterization of Prostate Cancer

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.

Study Overview

• Status: Recruiting
• Conditions: Prostate Cancer
• Intervention / Treatment: Diagnostic test: Apheresis; Other: Androgen deprivation therapy; Diagnostic test: Anti androgen therapy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 130
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Andreas Josefsson, MD, PhD; Phone Number: +46 70 3805395; Email: andreas.josefsson@umu.se

Study Locations

• Sweden
  • Norrlands University Hospital
    • Umeå, Norrlands University Hospital, Sweden, 90185
      • Recruiting
      • Department of surgical and perioperative sciences, Umeå university
      • Contact: Andreas Josefsson, MD, PhD; Phone Number: +46 70 3805395; Email: andreas.josefsson@umu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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:

• Venous blood vessels enabling apheresis
• ECOG-performance status 0-2
• Concentration of av potassium, calcium and magnesium in blood within normal range
• Testosterone>1,7 nmol/L
• Hb>90 g/L
• TPK >50x10exp9 /L
• LPK >1x10exp9 /L
• Bilirubin <1,4 x upper limit for normal (unless the subject suffers from Gilberts disease)
• ALAT or ASAT <2,4 x above limit for normal
• Creatinine <2 mg/dL (<177µmol/L)

Additional inclusion criteria for Arm 1 - Metastatic prostate cancer

One of the following criteria:

• PSA >100ng/ml
• Skeletal metastases with high risk of prostate cancer (regardless of PSA-value)

Additional inclusion criteria for Arm 2 - PSA relapse after operation

All of the three following criteria must be fulfilled:

• Prostatectomy
• PSA >0.2ng/ml
• PSA doubling time <18 months (according to www.mskcc.org/nomograms/prostate/psa_doubling_time)

Additional inclusion criteria for Arm 3 - Healthy research subjects (control group)

All of the following two criteria must be fulfilled:

• Previously healthy (no ongoing medication)
• No history of cancer

Exclusion Criteria for arm 1, 2 and 3:

• Overall, research subjects must not have any other cancer disease or risk factors for undergoing apheresis treatment
• Weight <50 kg
• Medical castration last 6 months (or previous surgical castration)
• Antiandrogen treatment in the last 6 months
• Previous myocardial infarction, stroke, chronic heart failure, atrial fibrillation or multiple deep vein thromboses
• Heart rate <45
• Systolic blood pressure below 100
• Ongoing diagnosed chronic inflammation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Primary metastatic prostate cancer; Men who have not previously received treatment for prostate cancer.	Diagnostic test: Apheresis; 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.; Other: Androgen deprivation therapy; 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.
Experimental: PSA relapse; Men with PSA recurrance after surgery.	Diagnostic test: Apheresis; 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.; Diagnostic test: Anti androgen therapy; 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.
Other: Healthy research subjects; Control group to distinguish tumor-specific changes from normal signals.	Diagnostic test: Apheresis; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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.

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Umeå University
• Investigators: Principal Investigator: Andreas Josefsson, MD, PhD, Department of surgical and perioperative sciences, Urology, Umeå University

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2020
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: March 17, 2023
• First Submitted That Met QC Criteria: November 26, 2024
• First Posted (Actual): November 29, 2024

Study Record Updates

• Last Update Posted (Actual): November 29, 2024
• Last Update Submitted That Met QC Criteria: November 26, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Micronutrients; Hormone Antagonists; Antioxidants; Protective Agents; Vitamins; Anabolic Agents; Estrogens; Methyltestosterone; Androgens; Ascorbic Acid; Androgen Antagonists; Estrogens, Conjugated (USP)
• Other Study ID Numbers: APACA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No