PRostate Cancer Plasma Integrative Multi-modal Evaluation

NCT06981377 | Recruiting DMC

• 1 other identifier: PRIME - AA Trento
• Study Type: observational
• Target: 800
• Locations: 1 country
• Sites: 4

Brief Summary

The study aims to develop PRIME (PRostate cancer plasma Integrative Multi-modal Evaluation) liquid biopsy test and to implement its use to query prospectively collected samples in advanced prostate cancer (PCa) clinical trials and/or clinical settings. In order to maximise the utility of liquid biopsies for advanced PCa, PRIME is focused on the development of novel computational and sequencing approaches that integrate multiple information from plasma circulating elements: i) cell free DNA (cfDNA) gene mutation data with accurate quantitation of cfDNA structural genomic changes, ii) cfDNA genomic profiling with cfDNA methylation status, and iii) the information provided by extracellular vesicles (EVs) and EV-associated cargo (including DNA, RNA and proteins).

Conditions

Metastatic Prostate Cancer

Keywords

Liquid biopsy; Cell free DNA (cfDNA); Extracellular Vesicles (EVs); Biomarkers

Outcome Measures

Primary Outcomes (5)

• Quantification of circulating tumor DNA (ctDNA) in the plasma

  Number of circulating tumor DNA (ctDNA) in the plasma

  From enrolment across different lines of treatment

• Quantification of the fraction of cfDNA hypo/hypermethylation

  Rate of cfDNA hypo/hypermethylation

  From enrolment across different lines of treatment

• Presence of recurrent somatic aberrations in ctDNA (such as loss of RB1, TP53, BRCA1/2, or AR amplification).

  Assessment (yes/no) of recurrent somatic aberrations in ctDNA (such as loss of RB1, TP53,

  From enrolment across different lines of treatment

• Presence of Copy Number Variants (CNVs) in ctDNA

  Assessment (yes/no) of Copy Number Variants (CNVs) in ctDNA

  From enrolment across different lines of treatment

• Identification of EV-associated biomarkers

  Assessment (yes/no) of EV-associated biomarkers

  From enrolment across different lines of treatment

Study Arms (2)

Metastatic Castration Resistant Prostate Cancer (mCRPC) patients

This group includes mCRPC patients treated with serial lines of treatment. For each line of treatment, blood samples are collected: 1. Before starting the treatment; 2. After 12 weeks; 3. At the end of the treatment/progression.

Diagnostic Test: Analysis of cell free DNA, and extracellular vesicles (EVs) and EV-associated molecular components (including RNA, DNA, proteins)

Metastatic Hormon Sensitive Prostate Cancer (mHSPC) patients

This group includes mHSPC patients treated with hormone therapy. In the hormone sensitive setting, blood samples are collected: 1. Before starting the treatment; 2. After 12 weeks; 3. Every six months until progression to the castration resistant status.

Diagnostic Test: Analysis of cell free DNA, and extracellular vesicles (EVs) and EV-associated molecular components (including RNA, DNA, proteins)

Interventions

Analysis of cell free DNA, and extracellular vesicles (EVs) and EV-associated molecular components (including RNA, DNA, proteins) DIAGNOSTIC_TEST

Plasma and buffy coat samples are shipped from the recruiting clinical sites to the lab of Professor Francesca Demichelis at the University of Trento (UniTN). At UniTN, samples are stored in dedicated freezers with restricted access and subsequently used as follows: * the plasma is used for the isolation of cell free DNA and extracellular vesicles (EVs); * the buffy coat is used for the extraction of genomic DNA. Nucleic acids sequencing library preparations and all downstream omics analyses are performed by Prof. Demichelis team.

Metastatic Castration Resistant Prostate Cancer (mCRPC) patients; Metastatic Hormon Sensitive Prostate Cancer (mHSPC) patients

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Patients are selected at oncology care clinics at participating clinical sites.

You may qualify if:

• Diagnosis of prostate cancer
• Eligible for prostate cancer pharmacological treatment
• Given consent to study participation

You may not qualify if:

• \- Histological diagnosis other than prostate cancer

Sponsors & Collaborators

• Santa Chiara Hospital: lead
• Università degli Studi di Trento: collaborator

Study Sites (4)

Istituto Romagnolo per lo Studio dei Tumori

Meldola, Forlì-Cesena, 47014, Italy

RECRUITING

Azienda Ospedaliera San Luigi

Orbassano, Torino, 10043, Italy

RECRUITING

Istituto Oncologico Veneto

Padua, 35128, Italy

RECRUITING

Santa Chiara Hospital

Trento, 38122, Italy

RECRUITING

Related Publications (12)

• Mugoni V, Ciani Y, Quaini O, Tomasini S, Notarangelo M, Vannuccini F, Marinelli A, Leonardi E, Pontalti S, Martinelli A, Rossetto D, Pesce I, Mansy SS, Barbareschi M, Ferro A, Caffo O, Attard G, Di Vizio D, D'Agostino VG, Nardella C, Demichelis F. Integrating extracellular vesicle and circulating cell-free DNA analysis using a single plasma aliquot improves the detection of HER2 positivity in breast cancer patients. J Extracell Biol. 2023 Sep;2(9):e108. doi: 10.1002/jex2.108. Epub 2023 Sep 25.

  PMID: 38046436 BACKGROUND

• Orlando F, Romanel A, Trujillo B, Sigouros M, Wetterskog D, Quaini O, Leone G, Xiang JZ, Wingate A, Tagawa S, Jayaram A, Linch M; PEACE Consortium; Jamal-Hanjani M, Swanton C, Rubin MA, Wyatt AW, Beltran H, Attard G, Demichelis F. Allele-informed copy number evaluation of plasma DNA samples from metastatic prostate cancer patients: the PCF_SELECT consortium assay. NAR Cancer. 2022 May 27;4(2):zcac016. doi: 10.1093/narcan/zcac016. eCollection 2022 Jun.

  PMID: 35664542 BACKGROUND

• Conteduca V, Scarpi E, Wetterskog D, Brighi N, Ferroni F, Rossi A, Romanel A, Gurioli G, Bleve S, Gianni C, Schepisi G, Lolli C, Cortesi P, Matteucci F, Barone D, Paganelli G, Demichelis F, Beltran H, Attard G, De Giorgi U. Plasma tumor DNA is associated with increased risk of venous thromboembolism in metastatic castration-resistant cancer patients. Int J Cancer. 2022 Apr 1;150(7):1166-1173. doi: 10.1002/ijc.33834. Epub 2021 Oct 13.

  PMID: 34605002 BACKGROUND

• Conteduca V, Wetterskog D, Scarpi E, Romanel A, Gurioli G, Jayaram A, Lolli C, Tandefelt DG, Schepisi G, Casadei C, Wingate A, Matteucci F, Paganelli G, Gonzalez-Billalabeitia E, Demichelis F, De Giorgi U, Attard G. Plasma tumour DNA as an early indicator of treatment response in metastatic castration-resistant prostate cancer. Br J Cancer. 2020 Sep;123(6):982-987. doi: 10.1038/s41416-020-0969-5. Epub 2020 Jul 16.

  PMID: 32669676 BACKGROUND

• Wu A, Cremaschi P, Wetterskog D, Conteduca V, Franceschini GM, Kleftogiannis D, Jayaram A, Sandhu S, Wong SQ, Benelli M, Salvi S, Gurioli G, Feber A, Pereira MB, Wingate AM, Gonzalez-Billalebeitia E, De Giorgi U, Demichelis F, Lise S, Attard G. Genome-wide plasma DNA methylation features of metastatic prostate cancer. J Clin Invest. 2020 Apr 1;130(4):1991-2000. doi: 10.1172/JCI130887.

  PMID: 32149736 BACKGROUND

• Beltran H, Romanel A, Conteduca V, Casiraghi N, Sigouros M, Franceschini GM, Orlando F, Fedrizzi T, Ku SY, Dann E, Alonso A, Mosquera JM, Sboner A, Xiang J, Elemento O, Nanus DM, Tagawa ST, Benelli M, Demichelis F. Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer. J Clin Invest. 2020 Apr 1;130(4):1653-1668. doi: 10.1172/JCI131041.

  PMID: 32091413 BACKGROUND

• Prandi D, Demichelis F. Ploidy- and Purity-Adjusted Allele-Specific DNA Analysis Using CLONETv2. Curr Protoc Bioinformatics. 2019 Sep;67(1):e81. doi: 10.1002/cpbi.81.

  PMID: 31524989 BACKGROUND

• Vagner T, Spinelli C, Minciacchi VR, Balaj L, Zandian M, Conley A, Zijlstra A, Freeman MR, Demichelis F, De S, Posadas EM, Tanaka H, Di Vizio D. Large extracellular vesicles carry most of the tumour DNA circulating in prostate cancer patient plasma. J Extracell Vesicles. 2018 Aug 7;7(1):1505403. doi: 10.1080/20013078.2018.1505403. eCollection 2018.

  PMID: 30108686 BACKGROUND

• Romanel A, Gasi Tandefelt D, Conteduca V, Jayaram A, Casiraghi N, Wetterskog D, Salvi S, Amadori D, Zafeiriou Z, Rescigno P, Bianchini D, Gurioli G, Casadio V, Carreira S, Goodall J, Wingate A, Ferraldeschi R, Tunariu N, Flohr P, De Giorgi U, de Bono JS, Demichelis F, Attard G. Plasma AR and abiraterone-resistant prostate cancer. Sci Transl Med. 2015 Nov 4;7(312):312re10. doi: 10.1126/scitranslmed.aac9511.

  PMID: 26537258 BACKGROUND

• Carreira S, Romanel A, Goodall J, Grist E, Ferraldeschi R, Miranda S, Prandi D, Lorente D, Frenel JS, Pezaro C, Omlin A, Rodrigues DN, Flohr P, Tunariu N, S de Bono J, Demichelis F, Attard G. Tumor clone dynamics in lethal prostate cancer. Sci Transl Med. 2014 Sep 17;6(254):254ra125. doi: 10.1126/scitranslmed.3009448.

  PMID: 25232177 BACKGROUND

• Prandi D, Baca SC, Romanel A, Barbieri CE, Mosquera JM, Fontugne J, Beltran H, Sboner A, Garraway LA, Rubin MA, Demichelis F. Unraveling the clonal hierarchy of somatic genomic aberrations. Genome Biol. 2014 Aug 26;15(8):439. doi: 10.1186/s13059-014-0439-6.

  PMID: 25160065 BACKGROUND

• Franceschini GM, Quaini O, Mizuno K, Orlando F, Ciani Y, Ku SY, Sigouros M, Rothmann E, Alonso A, Benelli M, Nardella C, Auh J, Freeman D, Hanratty B, Adil M, Elemento O, Tagawa ST, Feng FY, Caffo O, Buttigliero C, Basso U, Nelson PS, Corey E, Haffner MC, Attard G, Aparicio A, Demichelis F, Beltran H. Noninvasive Detection of Neuroendocrine Prostate Cancer through Targeted Cell-free DNA Methylation. Cancer Discov. 2024 Mar 1;14(3):424-445. doi: 10.1158/2159-8290.CD-23-0754.

  PMID: 38197680 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Plasma and buffy coat: * plasma is used for the isolation of cell free DNA (cfDNA) and extracellular Vesicles (EVs); * buffy coat is used for the extraction of genomic DNA (gDNA).

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

DNA, B-Form

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

DNA; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides; Nucleic Acid Conformation; Molecular Conformation; Molecular Structure; Biochemical Phenomena; Chemical Phenomena; Genetic Structures; Genetic Phenomena

Central Study Contacts

Orazio Caffo

CONTACT

+39 0461902121; orazio.caffo@apss.tn.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Medical Oncology Unit

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: May 20, 2025
• Study Start: May 7, 2019
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027
• Last Updated: May 20, 2025

Record last verified: 2025-05

Locations

IT (4)