Telomere Associated Variables (TAVs) in Prostate Cancer

NCT ID: NCT04124900

Last Updated: 2023-10-05

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 509 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-07-15
• Study Completion Date: 2023-09-21

Brief Summary

This research project results from the interest in continuing the collaboration with the previous LL-HURS-ONC001 clinical validation study, which gives cause to the present study. LL-HURS-ONC001 was carried out with the participation of HURS' Principal Investigator and the team of experts in prostate cancer, as well as with the participation of the Sponsor's scientific and development team, Life Length SL, led by Dr. Najarro.

The main objective of this study is to demonstrate the efficacy of the PROSTAV test in cutting down on unnecessary biopsies in prostate cancer screening/early diagnosis. PROSTAV is a minimally invasive test, easy to implement as biomarker for prostate cancer diagnosis. The efficacy of the PROSTAV test is clinically validated by the results obtained in a previous study, LL-HURS-ONC001.

The purpose of this study is to advance in the development of new biomarkers in areas where there is a clinical need and where the telomeric profile influences medical decisions within the patient's clinical context. The association level between each individual's telomere biology and the results of the prostate biopsy will be confirmed. Data will be collected to subsequently delve deeper into and accurately establish the effect of this measure in prostate cancer patient management to substantiate its implementation in standard care.

Detailed Description

In this study, patient inclusion and sample collection are multicentric. Sample analysis will be carried out at Life Length's laboratories at the Madrid Science Park in Canto Blanco university campus.

The study will be initiated immediately after approval by the IRB and has an overall length of 12 months (recruiting time).

The main purpose of the present study is to determine the efficacy of the PROSTAV test as a prostate cancer biomarker developed by Life Length and which has been subject to internal validation in a previous study (LL-HURS-ONC001). For this purpose, the risk-prediction algorithm based on telomere and clinical variables will be used. This allows to back medical decisions in patients with uncertain PC diagnosis based on their PSA levels and the need to perform a prostate biopsy. The standard of care of the participating hospitals and following the European Urology Association recommendations, patients with PSA >3 (prostate-specific antigen) and/or positive digital rectal examination (DRE) are considered at risk for developing PC. However, some medical advisors of the sponsor stated that sometimes patients with PSA levels<3 are also diagnosed with prostate cancer. For this reason, it has been decided to remove the lower limit of PSA as inclusion criteria.

This study includes only one group of patients defined by inclusion criteria and who will be classified in different groups after a biopsy is performed: 1) patients with a positive biopsy result (diagnosed with significant prostate cancer) (Gleason score >6), and without significant prostate cancer (Gleason score ≤6) or no cancer. Before knowing the histopathological results of the biopsy, the PROSTAV test will be performed. Depending on the results of the PROSTAV test, the physician will write down which decision he or she would have made as to performing or not a biopsy: zero (0) for a low-risk result in the PROSTAV test, in which case no biopsy would have been performed; and one (1) for a PC risk result in the PROSTAV test, in which case a biopsy would have been performed. Regardless of what the result of the PROSTAV test is, all patients will undergo a biopsy since the result in PROSTAV test will not influence the standard of care in this study.

A 10 ml. sample is required from all subjects included in the study for telomere analysis. This sample is obtained from blood drawn before performing the diagnostic prostate biopsy. The sample must be drawn within a 90-day period prior to biopsy.

The design of the present project allows for one single study phase. This study is a clinical efficacy validation study in patients in whom the results of potential biopsy sparing are compared after evaluating medical decisions based on the use of the PROSTAV test.

The point of origin of the samples are the different participating centers that will use the samples for application of the telomere biology evaluation techniques.

Mononuclear cells in peripheral blood from all samples will be isolated and analyzed to determine values of Telomere Associated Variables (TAVs).

For the calculation of the telomere variables, the Sponsor will use the High-Throughput Quantitative Fluorescent in Situ Hybridization technique (HT-Q-FISH).

Data resulting from each biological sample will be analyzed to obtain a defined risk assessment based on the algorithm of the PROSTAV test. The purpose of the analysis is the integration of the data resulting from telomere measurements (average, median, percentage of short telomeres, ratio of short and long telomeres, etc.) and PSA and free PSA levels, age and the DRE results of the patient's medical record to determine whether they are low-risk patients, in which a biopsy would not be necessary to confirm presence of prostate cancer. By doing this, it is intending to demonstrate the efficacy of the PROSTAV test, since biopsies would be performed in any case and also show the test's sensitivity and specificity values in clinical practice.

Conditions

Prostate Cancer

Study Design

• Observational Model Type: CASE_ONLY
• Study Time Perspective: PROSPECTIVE

Study Groups

patients at prostate cancer risk diagnosed

The study is composed of one single subject cohort. After risk evaluation, prostate biopsies will be performed for diagnostic purposes on all recruited patients. The cases are sorted into two groups after diagnosis:

• Group 1: patients at prostate cancer risk diagnosed with significant prostate cancer after prostatic biopsy (Gleason >6).
• Group 2: patients at prostate cancer risk diagnosed free of cancer after prostate biopsy. There will be a subdivision within this group in patients without significant prostate cancer ( No cancer o Non-significant prostate cancer (Gleason ≤6)).

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• To be over 18 years of age.
• To have given written consent to participate in the study.
• To be classified as a patient at prostate cancer risk according to criteria of high PSA levels (<10 ng/ml) and the urologist's decision to perform a prostate biopsy in standard of care.
• To be diagnosed by a prostate biopsy with or without concomitant MRI.
• Caucasic race

Exclusion Criteria

• Patients that have received Alpha-5 reductase therapy.
• Existing serious active liver, lung or kidney disease, as well as severe active infections.
• Existing serious disease or psychiatric disorder that prevents them from expressing informed consent and/or if patients are not able to follow protocol procedures and give their informed consent.
• Patients at risk resulting from conventional blood extraction.
• Subjects with active neoplasm diagnosed during the past five years.

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Life Length SL

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria José Requena

Role: PRINCIPAL_INVESTIGATOR

University Hospital Reina Sofía

Enrique Gómez, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital Reina Sofía

Locations

Urological Research Network, Corp.

Hialeah, Florida, United States

Houston Methodist Research Institute

Houston, Texas, United States

Hospital Infanta Margarita

Cabra, Córdoba, Spain

Instituto Médico Tecnológico

Barcelona, , Spain

University Hospital Reina Sofía

Córdoba, , Spain

ROC Clinic

Madrid, , Spain

Instituto de Urología LYX

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Universitario Doce de Octubre

Madrid, , Spain

Instituto Valenciano de Oncología

Valencia, , Spain

Countries

United States; Spain

References

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000 Jan 7;100(1):57-70. doi: 10.1016/s0092-8674(00)81683-9. No abstract available.

Reference Type: BACKGROUND

PMID: 10647931 (View on PubMed)

Shay JW, Wright WE, Werbin H. Defining the molecular mechanisms of human cell immortalization. Biochim Biophys Acta. 1991 Apr 16;1072(1):1-7. doi: 10.1016/0304-419x(91)90003-4.

Reference Type: BACKGROUND

PMID: 1850299 (View on PubMed)

Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA. Creation of human tumour cells with defined genetic elements. Nature. 1999 Jul 29;400(6743):464-8. doi: 10.1038/22780.

Reference Type: BACKGROUND

PMID: 10440377 (View on PubMed)

Wright WE, Shay JW. Telomere dynamics in cancer progression and prevention: fundamental differences in human and mouse telomere biology. Nat Med. 2000 Aug;6(8):849-51. doi: 10.1038/78592.

Reference Type: BACKGROUND

PMID: 10932210 (View on PubMed)

Shay JW, Zou Y, Hiyama E, Wright WE. Telomerase and cancer. Hum Mol Genet. 2001 Apr;10(7):677-85. doi: 10.1093/hmg/10.7.677.

Reference Type: BACKGROUND

PMID: 11257099 (View on PubMed)

Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, Coviello GM, Wright WE, Weinrich SL, Shay JW. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994 Dec 23;266(5193):2011-5. doi: 10.1126/science.7605428.

Reference Type: BACKGROUND

PMID: 7605428 (View on PubMed)

Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997 Apr;33(5):787-91. doi: 10.1016/S0959-8049(97)00062-2.

Reference Type: BACKGROUND

PMID: 9282118 (View on PubMed)

Breslow RA, Shay JW, Gazdar AF, Srivastava S. Telomerase and early detection of cancer: a National Cancer Institute workshop. J Natl Cancer Inst. 1997 May 7;89(9):618-23. doi: 10.1093/jnci/89.9.618. No abstract available.

Reference Type: BACKGROUND

PMID: 9150185 (View on PubMed)

Shay JW. Telomerase in cancer: diagnostic, prognostic, and therapeutic implications. Cancer J Sci Am. 1998 May;4 Suppl 1:S26-34. No abstract available.

Reference Type: BACKGROUND

PMID: 9619268 (View on PubMed)

Norton JC, Holt SE, Wright WE, Shay JW. Enhanced detection of human telomerase activity. DNA Cell Biol. 1998 Mar;17(3):217-9. doi: 10.1089/dna.1998.17.217.

Reference Type: BACKGROUND

PMID: 9539101 (View on PubMed)

Hiyama E, Hiyama K, Yokoyama T, Matsuura Y, Piatyszek MA, Shay JW. Correlating telomerase activity levels with human neuroblastoma outcomes. Nat Med. 1995 Mar;1(3):249-55. doi: 10.1038/nm0395-249.

Reference Type: BACKGROUND

PMID: 7585042 (View on PubMed)

Sommerfeld HJ, Meeker AK, Piatyszek MA, Bova GS, Shay JW, Coffey DS. Telomerase activity: a prevalent marker of malignant human prostate tissue. Cancer Res. 1996 Jan 1;56(1):218-22.

Reference Type: BACKGROUND

PMID: 8548767 (View on PubMed)

Mehle C, Piatyszek MA, Ljungberg B, Shay JW, Roos G. Telomerase activity in human renal cell carcinoma. Oncogene. 1996 Jul 4;13(1):161-6.

Reference Type: BACKGROUND

PMID: 8700542 (View on PubMed)

Tatsumoto N, Hiyama E, Murakami Y, Imamura Y, Shay JW, Matsuura Y, Yokoyama T. High telomerase activity is an independent prognostic indicator of poor outcome in colorectal cancer. Clin Cancer Res. 2000 Jul;6(7):2696-701.

Reference Type: BACKGROUND

PMID: 10914712 (View on PubMed)

Shay JW, Gazdar AF. Telomerase in the early detection of cancer. J Clin Pathol. 1997 Feb;50(2):106-9. doi: 10.1136/jcp.50.2.106.

Reference Type: BACKGROUND

PMID: 9155689 (View on PubMed)

Gurel B, Iwata T, Koh CM, Yegnasubramanian S, Nelson WG, De Marzo AM. Molecular alterations in prostate cancer as diagnostic, prognostic, and therapeutic targets. Adv Anat Pathol. 2008 Nov;15(6):319-31. doi: 10.1097/PAP.0b013e31818a5c19.

Reference Type: BACKGROUND

PMID: 18948763 (View on PubMed)

Heaphy CM, Meeker AK. The potential utility of telomere-related markers for cancer diagnosis. J Cell Mol Med. 2011 Jun;15(6):1227-38. doi: 10.1111/j.1582-4934.2011.01284.x.

Reference Type: BACKGROUND

PMID: 21352473 (View on PubMed)

Hou L, Joyce BT, Gao T, Liu L, Zheng Y, Penedo FJ, Liu S, Zhang W, Bergan R, Dai Q, Vokonas P, Hoxha M, Schwartz J, Baccarelli A. Blood Telomere Length Attrition and Cancer Development in the Normative Aging Study Cohort. EBioMedicine. 2015 Apr 13;2(6):591-6. doi: 10.1016/j.ebiom.2015.04.008. eCollection 2015 Jun.

Reference Type: BACKGROUND

PMID: 26288820 (View on PubMed)

Mottet N, Bellmunt J, Bolla M, Briers E, Cumberbatch MG, De Santis M, Fossati N, Gross T, Henry AM, Joniau S, Lam TB, Mason MD, Matveev VB, Moldovan PC, van den Bergh RCN, Van den Broeck T, van der Poel HG, van der Kwast TH, Rouviere O, Schoots IG, Wiegel T, Cornford P. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part 1: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol. 2017 Apr;71(4):618-629. doi: 10.1016/j.eururo.2016.08.003. Epub 2016 Aug 25.

Reference Type: BACKGROUND

PMID: 27568654 (View on PubMed)

Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part B: Prostate and Bladder Tumours. Eur Urol. 2016 Jul;70(1):106-119. doi: 10.1016/j.eururo.2016.02.028. Epub 2016 Mar 17.

Reference Type: BACKGROUND

PMID: 26996659 (View on PubMed)

Related Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5121784/pdf/jcdr-10-YE01.pdf

Requirements for Minimum Sample Size for Sensitivity and Specificity Analysis

Other Identifiers

PROSTAV001

Identifier Type: -

Identifier Source: org_study_id