PRostate Cancer Plasma Integrative Multi-modal Evaluation

Официальное название

Development of the PRIME Test for the Identification of Prostate Cancer Patients' Biomarkers Through Non-invasive Liquid Biopsies

Обзор

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).

Вмешательства

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

Первичные конечные точки

• Quantification of circulating tumor DNA (ctDNA) in the plasma [Срок оценки: From enrolment across different lines of treatment]
• Quantification of the fraction of cfDNA hypo/hypermethylation [Срок оценки: 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). [Срок оценки: From enrolment across different lines of treatment]
• Presence of Copy Number Variants (CNVs) in ctDNA [Срок оценки: From enrolment across different lines of treatment]
• Identification of EV-associated biomarkers [Срок оценки: From enrolment across different lines of treatment]

Критерии участия

Критерии включения

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

Критерии исключения

\- Histological diagnosis other than prostate cancer

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 4 центра

• Istituto Romagnolo per lo Studio dei Tumori — Meldola
• Azienda Ospedaliera San Luigi — Orbassano
• Istituto Oncologico Veneto — Padova
• Santa Chiara Hospital — Trento

Публикации

• 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 brea PMID 38046436
• 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):zcac PMID 35664542
• 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: PMID 34605002
• 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. PMID 32669676
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT06981377 · PRIME - AA Trento

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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