Analysis of Androgene Receptors Axis and DNA Damage Repair Genes in Patients With Prostate Cancer

NCT03677414 | Unknown

• 2 other identifiers: FWF Project KLI 710-B2621-228 ex 09/10
• Study Type: observational
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

In this project, we would like to focus on castration-sensitive prostate cancer (CRPC). This is a highly variable clinical picture with differentiated and burdening symptoms. The clinical parameters used to estimate the prognosis have so far only shown a very limited valence; genetic markers have so far only rarely been investigated. In the course of our preliminary investigations, we were already able to isolate 189 plasma samples from 59 patients with metastatic prostate cancer. These samples are prepared by highly innovative techniques, e.g. "whole genome sequencing", in order to gain comprehensive insights into the spectrum of genetic changes under therapy and the associated tumor evolution. These results should be compared with the genetic material of the respective prostate tumors, which originate from previous operations. This highly comprehensive data, which will yield results on copy number changes, mutations, and gene expression, will allow analysis of signaling pathways of unprecedented resolution to increase the efficacy of targeted therapies in patients and minimize the burden of non-effective therapy side effects.

Conditions

Prostatic Neoplasms

Keywords

circulating-tumor DNA ctDNA

Outcome Measures

Primary Outcomes (1)

• Nucleosome positioning patterns

  Here, samples with increased z-score (z-score \>5; corresponds to ≥10% ctDNA; modified Fast Aneuploidy Screening Test-Sequencing System (mFAST-SeqS)) will be sequenced with high coverage (70x) so that nucleosome positions can be extracted from the obtained sequences. As at TSSs (transcriptional start site), the nucleosome occupancy results in different read-depth coverage patterns in expressed and silent genes (Ulz et al., Nat Genet 2016), systematic maps of nucleosome positions in defined patients will be generated.

  3 years

Secondary Outcomes (5)

• Focal amplifications in ctDNA

  3 years

• Prostate Cancer Panel

  3 years

• Clinico-pathological characteristics

  3 years

• Analyses of primary tumors

  3 years

• Buccal swap

  3 years

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: The study includes men with metastasized prostate cancer.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study includes men with proven histological diagnosis of prostate cancer and treatment with abiraterone and/or enzalutamide. Participants were recruited at the Medical University Hospital of Graz.

You may qualify if:

• subject has proven histological diagnosis of prostate cancer
• subject was treated with abiraterone and/or enzalutamide.

You may not qualify if:

• patient rejects the participation

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Institute of Human Genetics, Medical University of Graz

Graz, 8010, Austria

Location

Related Publications (4)

• Ulz P, Belic J, Graf R, Auer M, Lafer I, Fischereder K, Webersinke G, Pummer K, Augustin H, Pichler M, Hoefler G, Bauernhofer T, Geigl JB, Heitzer E, Speicher MR. Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer. Nat Commun. 2016 Jun 22;7:12008. doi: 10.1038/ncomms12008.

  PMID: 27328849 BACKGROUND

• Ulz P, Heitzer E, Speicher MR. Co-occurrence of MYC amplification and TP53 mutations in human cancer. Nat Genet. 2016 Feb;48(2):104-6. doi: 10.1038/ng.3468. No abstract available.

  PMID: 26813759 BACKGROUND

• Ulz P, Thallinger GG, Auer M, Graf R, Kashofer K, Jahn SW, Abete L, Pristauz G, Petru E, Geigl JB, Heitzer E, Speicher MR. Inferring expressed genes by whole-genome sequencing of plasma DNA. Nat Genet. 2016 Oct;48(10):1273-8. doi: 10.1038/ng.3648. Epub 2016 Aug 29.

  PMID: 27571261 BACKGROUND

• Maia MC, Salgia M, Pal SK. Harnessing cell-free DNA: plasma circulating tumour DNA for liquid biopsy in genitourinary cancers. Nat Rev Urol. 2020 May;17(5):271-291. doi: 10.1038/s41585-020-0297-9. Epub 2020 Mar 17.

  PMID: 32203306 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Plasma DNA Primary tumor Buccal swap

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Study Officials

• Jochen B Geigl, Prof, MD

  Institute of Human Genetics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2018
• First Posted: September 19, 2018
• Study Start: September 10, 2018
• Primary Completion: January 31, 2021
• Study Completion: August 31, 2021
• Last Updated: September 19, 2018

Record last verified: 2018-09

Locations

AU (1)