Novel Therapy Target in Metastatic Prostate Cancer

Prostate Neoplasms Clinical Trial

— NTTPro  

Official title:

Combining Multi-omics Analysis and Organoid Models to Search for Novel Therapy Target in Metastatic Prostate Cancer

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05577689
• Other study ID #: PCa-Organoid
• Status: Not yet recruiting
• Start date: March 1, 2023
• Est. completion date: May 1, 2026

Study information

• Verified date: October 2022
• Source: Fudan University
• Contact: Yao Zhu
• Phone: +86 15001818005
• Email: mailzhuyao[@]163.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The aim of this study is to use multiomics sequencing to explore the molecular characteristics of metastatic prostate cancer (mPCa), especially metastatic castration-resistant prostate cancer (mCRPC). At the same time, mCRPC models will be constructed, including organoids and animal models, serving as a basic and translational research platform to help identify novel drug targets for mPCa.

Description:

Although substantial progress in treatments for prostate cancer have been made in the past decades, distant metastasis and drug resistance remained a major cause of prostate cancer-related deaths. The five-year survival rate for men with mPCa was only 30% and all patients with mPCa would inevitably progress to the castration-resistant stage with limited therapeutic chance. In China, the current situation is more worrying, with rapidly increasing PCa incidence and higher proportion of mPCa diagnosed compared with the Western nations (~30% vs ~5%).

Multiomics sequencing provides a promising strategy to discover the underlying molecular basis driving metastasis and resistance and identify the new treatment strategies for patients with mCRPC. The candidate drug target revealed by the multiomics sequencing could be further examined in the organoid and animal models, facilitating the clinical application from basic discovery.

This study can establish a mCRPC research system to find the molecular mechanism and potential intervention targets of mCRPC, thereby paving the way for the discovery of new treatments for mCRPC patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: May 1, 2026
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Histologically confirmed prostate cancer

2. metastatic disease confirmed by image examination

3. Patients who can undergo surgery or biopsy for prostate cancer

4. Able to provide informed consent

Exclusion Criteria:

1. Patients diagnosed with other types of cancer besides prostate cancer

2. Not accessible to surgery sample

3. Patients fail to provide informed consent

4. Other situation that researchers think are unsuitable for this study

Related Conditions & MeSH terms

• Prostate Neoplasms
• Prostatic Neoplasms

Intervention

Other:
• Tissue
Tissue will be derived from patients during a standard of care procedure

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fudan University

References & Publications (6)

Akhoundova D, Rubin MA. Clinical application of advanced multi-omics tumor profiling: Shaping precision oncology of the future. Cancer Cell. 2022 Sep 12;40(9):920-938. doi: 10.1016/j.ccell.2022.08.011. Epub 2022 Sep 1. Review. — View Citation

Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, Dowling C, Wanjala JN, Undvall EA, Arora VK, Wongvipat J, Kossai M, Ramazanoglu S, Barboza LP, Di W, Cao Z, Zhang QF, Sirota I, Ran L, MacDonald TY, Beltran H, Mosquera JM, Touijer KA, Scardino PT, Laudone VP, Curtis KR, Rathkopf DE, Morris MJ, Danila DC, Slovin SF, Solomon SB, Eastham JA, Chi P, Carver B, Rubin MA, Scher HI, Clevers H, Sawyers CL, Chen Y. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014 Sep 25;159(1):176-187. doi: 10.1016/j.cell.2014.08.016. Epub 2014 Sep 4. — View Citation

Guo C, Figueiredo I, Gurel B, Neeb A, Seed G, Crespo M, Carreira S, Rekowski J, Buroni L, Welti J, Bogdan D, Gallagher L, Sharp A, Fenor de la Maza MD, Rescigno P, Westaby D, Chandran K, Riisnaes R, Ferreira A, Miranda S, Calì B, Alimonti A, Bressan S, Nguyen AHT, Shen MM, Hawley JE, Obradovic A, Drake CG, Bertan C, Baker C, Tunariu N, Yuan W, de Bono JS. B7-H3 as a Therapeutic Target in Advanced Prostate Cancer. Eur Urol. 2022 Sep 13. pii: S0302-2838(22)02633-1. doi: 10.1016/j.eururo.2022.09.004. [Epub ahead of print] — View Citation

Wei Y, Wu J, Gu W, Qin X, Dai B, Lin G, Gan H, Freedland SJ, Zhu Y, Ye D. Germline DNA Repair Gene Mutation Landscape in Chinese Prostate Cancer Patients. Eur Urol. 2019 Sep;76(3):280-283. doi: 10.1016/j.eururo.2019.06.004. Epub 2019 Jun 24. Review. — View Citation

Yerly L, Pich-Bavastro C, Di Domizio J, Wyss T, Tissot-Renaud S, Cangkrama M, Gilliet M, Werner S, Kuonen F. Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma. Nat Commun. 2022 Aug 20;13(1):4897. doi: 10.1038/s41467-022-32670-w. — View Citation

Zhu Y, Mo M, Wei Y, Wu J, Pan J, Freedland SJ, Zheng Y, Ye D. Epidemiology and genomics of prostate cancer in Asian men. Nat Rev Urol. 2021 May;18(5):282-301. doi: 10.1038/s41585-021-00442-8. Epub 2021 Mar 10. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Multiple omics features	Multi-omics information including genetic profiling results, transcriptional profiling results and epigenomic profiling results will be collected and analyzed.	3 years
Primary	Organoids successfully generated from metastatic prostate cancer	Successful isolation of prostate cancer organoids from surgical specimens of patients diagnosed with metastatic prostate cancer. We will calculate the culture efficiency and total number of organoids generated in our center.	3 years
Primary	Developing of biomarkers related to cancer metastasis and drug resistant	To search for biomarkers related to tumor metastasis and resistance by performing multi-omics analysis to surgery specimens derived from patients with metastatic prostate cancer.	3 years
Secondary	Animal models successfully generated from patient derived prostate cancer organoids	Prostate cancer organoids with clarified characteristics will be transplanted into mice to establish PDOX models.	3 years
Secondary	Response of the prostate cancer organoids to the selected anti-cancer compounds	Organoid that are successfully cultured and characteristic clarified will be treated with the selected compounds to test their anti-cancer activity.	3 years
Secondary	Response of the PDOX models to the selected anti-cancer compounds	PDOX models that successfully established will be treated with the selected compounds to test their anti-cancer activity.	3 years