Telmisartan in Prostate Cancer

Summary

The goal of this clinical trial is to learn about the tolerability of telmisartan in patients with prostate cancer, but evidence for treatment efficacy will also be gathered.

Timeline

Start

2024-04-22

Primary completion

2026-04-01

Completion

2027-04-01

Publications

• Background SEER*Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute; 2023 Apr 19. Available from: https://seer.cancer.gov/statistics-network/explorer/. Data source(s): SEER Incidence Data, November 2022 Submission (1975-2020), SEER 22 registries. updated: 2023 Jun 8. Accessed Oct 5, 2023
• Background Smith MR, Saad F, Rathkopf DE, Mulders PFA, de Bono JS, Small EJ, Shore ND, Fizazi K, Kheoh T, Li J, De Porre P, Todd MB, Yu MK, Ryan CJ. Clinical Outcomes from Androgen Signaling-directed Therapy after Treatment with Abiraterone Acetate and Prednisone in Patients with Metastatic Castration-resistant Prostate Cancer: Post Hoc Analysis of COU-AA-302. Eur Urol. 2017 Jul;72(1):10-13. doi: 10.1016/j.eururo.2017.03.007. Epub 2017 Mar 15.
• Background Chen K, O'Brien J, McVey A, Jenjitranant P, Kelly BD, Kasivisvanathan V, Lawrentschuk N, Murphy DG, Azad AA. Combination treatment in metastatic prostate cancer: is the bar too high or have we fallen short? Nat Rev Urol. 2023 Feb;20(2):116-123. doi: 10.1038/s41585-022-00669-z. Epub 2022 Dec 12.
• Background Sayegh N, Swami U, Agarwal N. Recent Advances in the Management of Metastatic Prostate Cancer. JCO Oncol Pract. 2022 Jan;18(1):45-55. doi: 10.1200/OP.21.00206. Epub 2021 Sep 2.
• Background Asim M, Tarish F, Zecchini HI, Sanjiv K, Gelali E, Massie CE, Baridi A, Warren AY, Zhao W, Ogris C, McDuffus LA, Mascalchi P, Shaw G, Dev H, Wadhwa K, Wijnhoven P, Forment JV, Lyons SR, Lynch AG, O'Neill C, Zecchini VR, Rennie PS, Baniahmad A, Tavare S, Mills IG, Galanty Y, Crosetto N, Schultz N, Neal D, Helleday T. Synthetic lethality between androgen receptor signalling and the PARP pathway in prostate cancer. Nat Commun. 2017 Aug 29;8(1):374. doi: 10.1038/s41467-017-00393-y.
• Background Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, Arslan C, Mehra N, Parnis F, Brown E, Schlurmann F, Joung JY, Sugimoto M, Sartor O, Liu YZ, Poehlein C, Barker L, Del Rosario PM, Armstrong AJ. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Oct;24(10):1094-1108. doi: 10.1016/S1470-2045(23)00382-0. Epub 2023 Sep 12.
• Background Murray C, Bai H, Ontiveros CO, et al. Pharmacologic tumor PDL1 depletion as a novel approach to overcome treatment resistance. The Journal of Immunology. 2023;210(1_Supplement):230.08-230.08. doi:10.4049/jimmunol.210.Supp.230.08
• Background Uemura H, Miyoshi Y, Ishiguro H, Nakaigawa N, Noguchi K, Kubota Y. Effectiveness of angionten II receptor blocker (ARB), candesartan, in the treatment of hormone refractory prostate cancer (HRPC). presented at: 2004 ASCO Annual Meeting; 2004
• Background Wang C, Wang WB. Telmisartan Induces Osteosarcoma Cells Growth Inhibition and Apoptosis Via Suppressing mTOR Pathway. Open Life Sci. 2018 Jul 5;13:242-249. doi: 10.1515/biol-2018-0029. eCollection 2018 Jan.
• Background Scher HI, Morris MJ, Stadler WM, Higano C, Basch E, Fizazi K, Antonarakis ES, Beer TM, Carducci MA, Chi KN, Corn PG, de Bono JS, Dreicer R, George DJ, Heath EI, Hussain M, Kelly WK, Liu G, Logothetis C, Nanus D, Stein MN, Rathkopf DE, Slovin SF, Ryan CJ, Sartor O, Small EJ, Smith MR, Sternberg CN, Taplin ME, Wilding G, Nelson PS, Schwartz LH, Halabi S, Kantoff PW, Armstrong AJ; Prostate Cancer Clinical Trials Working Group 3. Trial Design and Objectives for Castration-Resistant Prostate Cancer: Updated Recommendations From the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol. 2016 Apr 20;34(12):1402-18. doi: 10.1200/JCO.2015.64.2702. Epub 2016 Feb 22.
• Background Jensterle M, Janez A, Vrtovec B, Meden-Vrtovec H, Pfeifer M, Prezelj J, Kocjan T. Decreased androgen levels and improved menstrual pattern after angiotensin II receptor antagonist telmisartan treatment in four hypertensive patients with polycystic ovary syndrome: case series. Croat Med J. 2007 Dec;48(6):864-70. doi: 10.3325/cmj.2007.6.864.
• Background McAlister FA; Renin Angiotension System Modulator Meta-Analysis Investigators. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are beneficial in normotensive atherosclerotic patients: a collaborative meta-analysis of randomized trials. Eur Heart J. 2012 Feb;33(4):505-14. doi: 10.1093/eurheartj/ehr400. Epub 2011 Oct 31.
• Background Galle J. Reduction of proteinuria with angiotensin receptor blockers. Nat Clin Pract Cardiovasc Med. 2008 Jul;5 Suppl 1:S36-43. doi: 10.1038/ncpcardio0806.
• Background Qaisar R, Kamli H, Karim A, Muhammad T, Ahmad F, Shaikh A. Angiotensin Receptor Blockers Restore Skeletal Muscle in Patients with Chronic Obstructive Pulmonary Disease. Arch Med Res. 2023 Nov;54(7):102890. doi: 10.1016/j.arcmed.2023.102890. Epub 2023 Sep 21.
• Background Fang T, Zhang J, Zuo T, Wu G, Xu Y, Yang Y, Yang J, Shen Q. Chemo-Photothermal Combination Cancer Therapy with ROS Scavenging, Extracellular Matrix Depletion, and Tumor Immune Activation by Telmisartan and Diselenide-Paclitaxel Prodrug Loaded Nanoparticles. ACS Appl Mater Interfaces. 2020 Jul 15;12(28):31292-31308. doi: 10.1021/acsami.0c10416. Epub 2020 Jul 1.
• Background Zhu Y, Yu F, Tan Y, Hong Y, Meng T, Liu Y, Dai S, Qiu G, Yuan H, Hu F. Reversing activity of cancer associated fibroblast for staged glycolipid micelles against internal breast tumor cells. Theranostics. 2019 Sep 19;9(23):6764-6779. doi: 10.7150/thno.36334. eCollection 2019.
• Background Kobara H, Fujihara S, Iwama H, Matsui T, Fujimori A, Chiyo T, Tingting S, Kobayashi N, Nishiyama N, Yachida T, Tadokoro T, Oura K, Tani J, Fujita K, Nomura T, Yoneyama H, Morishita A, Okano K, Suzuki Y, Mori H, Masaki T. Antihypertensive drug telmisartan inhibits cell proliferation of gastrointestinal stromal tumor cells in vitro. Mol Med Rep. 2020 Aug;22(2):1063-1071. doi: 10.3892/mmr.2020.11144. Epub 2020 May 14.
• Background Fujita N, Fujita K, Iwama H, Kobara H, Fujihara S, Chiyo T, Namima D, Yamana H, Kono T, Takuma K, Hirata M, Kobayashi K, Kato K, Kamada H, Morishita A, Tsutsui K, Himoto T, Okano K, Suzuki Y, Masaki T. Antihypertensive drug telmisartan suppresses the proliferation of gastric cancer cells in vitro and in vivo. Oncol Rep. 2020 Jul;44(1):339-348. doi: 10.3892/or.2020.7607. Epub 2020 May 7.
• Background Uemura H, Ishiguro H, Nakaigawa N, Nagashima Y, Miyoshi Y, Fujinami K, Sakaguchi A, Kubota Y. Angiotensin II receptor blocker shows antiproliferative activity in prostate cancer cells: a possibility of tyrosine kinase inhibitor of growth factor. Mol Cancer Ther. 2003 Nov;2(11):1139-47.
• Background Wu TT, Niu HS, Chen LJ, Cheng JT, Tong YC. Increase of human prostate cancer cell (DU145) apoptosis by telmisartan through PPAR-delta pathway. Eur J Pharmacol. 2016 Mar 15;775:35-42. doi: 10.1016/j.ejphar.2016.02.017. Epub 2016 Feb 4.
• Background Takahashi S, Uemura H, Seeni A, Tang M, Komiya M, Long N, Ishiguro H, Kubota Y, Shirai T. Therapeutic targeting of angiotensin II receptor type 1 to regulate androgen receptor in prostate cancer. Prostate. 2012 Oct 1;72(14):1559-72. doi: 10.1002/pros.22505. Epub 2012 Mar 16.
• Background Mariniello M, Petruzzelli R, Wanderlingh LG, La Montagna R, Carissimo A, Pane F, Amoresano A, Ilyechova EY, Galagudza MM, Catalano F, Crispino R, Puchkova LV, Medina DL, Polishchuk RS. Synthetic Lethality Screening Identifies FDA-Approved Drugs that Overcome ATP7B-Mediated Tolerance of Tumor Cells to Cisplatin. Cancers (Basel). 2020 Mar 6;12(3):608. doi: 10.3390/cancers12030608.
• Background Green R, Howell M, Khalil R, Nair R, Yan J, Foran E, Katiri S, Banerjee J, Singh M, Bharadwaj S, Mohapatra SS, Mohapatra S. Actinomycin D and Telmisartan Combination Targets Lung Cancer Stem Cells Through the Wnt/Beta Catenin Pathway. Sci Rep. 2019 Dec 3;9(1):18177. doi: 10.1038/s41598-019-54266-z.
• Background Rasheduzzaman M, Moon JH, Lee JH, Nazim UM, Park SY. Telmisartan generates ROS-dependent upregulation of death receptor 5 to sensitize TRAIL in lung cancer via inhibition of autophagy flux. Int J Biochem Cell Biol. 2018 Sep;102:20-30. doi: 10.1016/j.biocel.2018.06.006. Epub 2018 Jun 19.
• Background Grahovac J, Srdic-Rajic T, Francisco Santibanez J, Pavlovic M, Cavic M, Radulovic S. Telmisartan induces melanoma cell apoptosis and synergizes with vemurafenib in vitro by altering cell bioenergetics. Cancer Biol Med. 2019 May;16(2):247-263. doi: 10.20892/j.issn.2095-3941.2018.0375.
• Background Samukawa E, Fujihara S, Oura K, Iwama H, Yamana Y, Tadokoro T, Chiyo T, Kobayashi K, Morishita A, Nakahara M, Kobara H, Mori H, Okano K, Suzuki Y, Himoto T, Masaki T. Angiotensin receptor blocker telmisartan inhibits cell proliferation and tumor growth of cholangiocarcinoma through cell cycle arrest. Int J Oncol. 2017 Dec;51(6):1674-1684. doi: 10.3892/ijo.2017.4177. Epub 2017 Oct 23.
• Background Oura K, Tadokoro T, Fujihara S, Morishita A, Chiyo T, Samukawa E, Yamana Y, Fujita K, Sakamoto T, Nomura T, Yoneyama H, Kobara H, Mori H, Iwama H, Okano K, Suzuki Y, Masaki T. Telmisartan inhibits hepatocellular carcinoma cell proliferation in vitro by inducing cell cycle arrest. Oncol Rep. 2017 Nov;38(5):2825-2835. doi: 10.3892/or.2017.5977. Epub 2017 Sep 20.
• Background Fujihara S, Morishita A, Ogawa K, Tadokoro T, Chiyo T, Kato K, Kobara H, Mori H, Iwama H, Masaki T. The angiotensin II type 1 receptor antagonist telmisartan inhibits cell proliferation and tumor growth of esophageal adenocarcinoma via the AMPKalpha/mTOR pathway in vitro and in vivo. Oncotarget. 2017 Jan 31;8(5):8536-8549. doi: 10.18632/oncotarget.14345.
• Background Pu Z, Zhu M, Kong F. Telmisartan prevents proliferation and promotes apoptosis of human ovarian cancer cells through upregulating PPARgamma and downregulating MMP-9 expression. Mol Med Rep. 2016 Jan;13(1):555-9. doi: 10.3892/mmr.2015.4512. Epub 2015 Nov 6.
• Background de Araujo Junior RF, Leitao Oliveira AL, de Melo Silveira RF, de Oliveira Rocha HA, de Franca Cavalcanti P, de Araujo AA. Telmisartan induces apoptosis and regulates Bcl-2 in human renal cancer cells. Exp Biol Med (Maywood). 2015 Jan;240(1):34-44. doi: 10.1177/1535370214546267. Epub 2014 Aug 14.
• Background Ozeki K, Tanida S, Morimoto C, Inoue Y, Mizoshita T, Tsukamoto H, Shimura T, Kataoka H, Kamiya T, Nishiwaki E, Ishiguro H, Higashiyama S, Joh T. Telmisartan inhibits cell proliferation by blocking nuclear translocation of ProHB-EGF C-terminal fragment in colon cancer cells. PLoS One. 2013;8(2):e56770. doi: 10.1371/journal.pone.0056770. Epub 2013 Feb 22.
• Background Koyama N, Nishida Y, Ishii T, Yoshida T, Furukawa Y, Narahara H. Telmisartan induces growth inhibition, DNA double-strand breaks and apoptosis in human endometrial cancer cells. PLoS One. 2014 Mar 25;9(3):e93050. doi: 10.1371/journal.pone.0093050. eCollection 2014.
• Background Kornepati AVR, Boyd JT, Murray CE, Saifetiarova J, de la Pena Avalos B, Rogers CM, Bai H, Padron AS, Liao Y, Ontiveros C, Svatek RS, Hromas R, Li R, Hu Y, Conejo-Garcia JR, Vadlamudi RK, Zhao W, Dray E, Sung P, Curiel TJ. Tumor Intrinsic PD-L1 Promotes DNA Repair in Distinct Cancers and Suppresses PARP Inhibitor-Induced Synthetic Lethality. Cancer Res. 2022 Jun 6;82(11):2156-2170. doi: 10.1158/0008-5472.CAN-21-2076.
• Background Nair AB, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016 Mar;7(2):27-31. doi: 10.4103/0976-0105.177703.
• Background Daniel B, Nagy G, Czimmerer Z, Horvath A, Hammers DW, Cuaranta-Monroy I, Poliska S, Tzerpos P, Kolostyak Z, Hays TT, Patsalos A, Houtman R, Sauer S, Francois-Deleuze J, Rastinejad F, Balint BL, Sweeney HL, Nagy L. The Nuclear Receptor PPARgamma Controls Progressive Macrophage Polarization as a Ligand-Insensitive Epigenomic Ratchet of Transcriptional Memory. Immunity. 2018 Oct 16;49(4):615-626.e6. doi: 10.1016/j.immuni.2018.09.005.
• Background Kornepati AVR, Rogers CM, Sung P, Curiel TJ. The complementarity of DDR, nucleic acids and anti-tumour immunity. Nature. 2023 Jul;619(7970):475-486. doi: 10.1038/s41586-023-06069-6. Epub 2023 Jul 19.
• Background Washida K, Ihara M, Nishio K, Fujita Y, Maki T, Yamada M, Takahashi J, Wu X, Kihara T, Ito H, Tomimoto H, Takahashi R. Nonhypotensive dose of telmisartan attenuates cognitive impairment partially due to peroxisome proliferator-activated receptor-gamma activation in mice with chronic cerebral hypoperfusion. Stroke. 2010 Aug;41(8):1798-806. doi: 10.1161/STROKEAHA.110.583948. Epub 2010 Jul 1.
• Background Torika N, Asraf K, Danon A, Apte RN, Fleisher-Berkovich S. Telmisartan Modulates Glial Activation: In Vitro and In Vivo Studies. PLoS One. 2016 May 17;11(5):e0155823. doi: 10.1371/journal.pone.0155823. eCollection 2016.
• Background Hartley A, Ahmad I. The role of PPARgamma in prostate cancer development and progression. Br J Cancer. 2023 Apr;128(6):940-945. doi: 10.1038/s41416-022-02096-8. Epub 2022 Dec 12.
• Background Khorsand M, Khajeh S, Eslami M, Nezafat N, Ghasemi Y, Razban V, Mostafavi-Pour Z. Telmisartan anti-cancer activities mechanism through targeting N-cadherin by mimicking ADH-1 function. J Cell Mol Med. 2022 Apr;26(8):2392-2403. doi: 10.1111/jcmm.17259. Epub 2022 Feb 27.
• Background Cernes R, Mashavi M, Zimlichman R. Differential clinical profile of candesartan compared to other angiotensin receptor blockers. Vasc Health Risk Manag. 2011;7:749-59. doi: 10.2147/VHRM.S22591. Epub 2011 Dec 12.
• Background Uemura H, Hasumi H, Kawahara T, Sugiura S, Miyoshi Y, Nakaigawa N, Teranishi J, Noguchi K, Ishiguro H, Kubota Y. Pilot study of angiotensin II receptor blocker in advanced hormone-refractory prostate cancer. Int J Clin Oncol. 2005 Dec;10(6):405-10. doi: 10.1007/s10147-005-0520-y.
• Background Funao K, Matsuyama M, Kawahito Y, Sano H, Chargui J, Touraine JL, Nakatani T, Yoshimura R. Telmisartan is a potent target for prevention and treatment in human prostate cancer. Oncol Rep. 2008 Aug;20(2):295-300.
• Background Uemura H, Kubota Y. [Application of angiotensin II receptor blocker in prostate cancer]. Nihon Rinsho. 2009 Apr;67(4):807-11. Japanese.
• Background Tascilar K, Azoulay L, Dell'Aniello S, Bartels DB, Suissa S. The Use of Telmisartan and the Incidence of Cancer. Am J Hypertens. 2016 Dec 1;29(12):1358-1365. doi: 10.1093/ajh/hpw095.
• Background Wilk M, Wasko-Grabowska A, Skoneczna I, Szmit S. Angiotensin System Inhibitors May Improve Outcomes of Patients With Castration-Resistant Prostate Cancer During Abiraterone Acetate Treatment-A Cardio-Oncology Study. Front Oncol. 2021 Apr 1;11:664741. doi: 10.3389/fonc.2021.664741. eCollection 2021.
• Background Rudolph J, Jung K, Luger K. Inhibitors of PARP: Number crunching and structure gazing. Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2121979119. doi: 10.1073/pnas.2121979119. Epub 2022 Mar 8.
• Background LaFargue CJ, Dal Molin GZ, Sood AK, Coleman RL. Exploring and comparing adverse events between PARP inhibitors. Lancet Oncol. 2019 Jan;20(1):e15-e28. doi: 10.1016/S1470-2045(18)30786-1.

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Indications