Telmisartan in Combination With Cytotoxic Regimens in Platinum-Resistant Ovarian Cancer

Summary

The primary study objective is to assess progression-free survival in patients with ovarian cancer receiving telmisartan plus selected standard of care chemotherapy regimens versus historical controls.

Timeline

Start

2026-01-21

Primary completion

2027-04-14

Completion

2029-05-14

Publications

• Background Richardson DL, Eskander RN, O'Malley DM. Advances in Ovarian Cancer Care and Unmet Treatment Needs for Patients With Platinum Resistance: A Narrative Review. JAMA Oncol. 2023 Jun 1;9(6):851-859. doi: 10.1001/jamaoncol.2023.0197.
• Background Moore KN, Angelergues A, Konecny GE, Garcia Y, Banerjee S, Lorusso D, Lee JY, Moroney JW, Colombo N, Roszak A, Tromp J, Myers T, Lee JW, Beiner M, Cosgrove CM, Cibula D, Martin LP, Sabatier R, Buscema J, Estevez-Garcia P, Coffman L, Nicum S, Duska LR, Pignata S, Galvez F, Wang Y, Method M, Berkenblit A, Bello Roufai D, Van Gorp T; Gynecologic Oncology Group Partners and the European Network of Gynaecological Oncological Trial Groups. Mirvetuximab Soravtansine in FRalpha-Positive, Platinum-Resistant Ovarian Cancer. N Engl J Med. 2023 Dec 7;389(23):2162-2174. doi: 10.1056/NEJMoa2309169.
• Background Mellman I, Chen DS, Powles T, Turley SJ. The cancer-immunity cycle: Indication, genotype, and immunotype. Immunity. 2023 Oct 10;56(10):2188-2205. doi: 10.1016/j.immuni.2023.09.011.
• Background Drerup JM, Liu Y, Padron AS, Murthy K, Hurez V, Zhang B, Curiel TJ. Immunotherapy for ovarian cancer. Curr Treat Options Oncol. 2015 Jan;16(1):317. doi: 10.1007/s11864-014-0317-1.
• Background Palaia I, Tomao F, Sassu CM, Musacchio L, Benedetti Panici P. Immunotherapy For Ovarian Cancer: Recent Advances And Combination Therapeutic Approaches. Onco Targets Ther. 2020 Jun 26;13:6109-6129. doi: 10.2147/OTT.S205950. eCollection 2020.
• Background Muaibati M, Abuduyilimu A, Zhang T, Dai Y, Li R, Huang F, Li K, Tong Q, Huang X, Zhuang L. Efficacy of immune checkpoint inhibitor monotherapy or combined with other small molecule-targeted agents in ovarian cancer. Expert Rev Mol Med. 2023 Jan 24;25:e6. doi: 10.1017/erm.2023.3.
• Background Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SA, Behjati S, Biankin AV, Bignell GR, Bolli N, Borg A, Borresen-Dale AL, Boyault S, Burkhardt B, Butler AP, Caldas C, Davies HR, Desmedt C, Eils R, Eyfjord JE, Foekens JA, Greaves M, Hosoda F, Hutter B, Ilicic T, Imbeaud S, Imielinski M, Jager N, Jones DT, Jones D, Knappskog S, Kool M, Lakhani SR, Lopez-Otin C, Martin S, Munshi NC, Nakamura H, Northcott PA, Pajic M, Papaemmanuil E, Paradiso A, Pearson JV, Puente XS, Raine K, Ramakrishna M, Richardson AL, Richter J, Rosenstiel P, Schlesner M, Schumacher TN, Span PN, Teague JW, Totoki Y, Tutt AN, Valdes-Mas R, van Buuren MM, van 't Veer L, Vincent-Salomon A, Waddell N, Yates LR; Australian Pancreatic Cancer Genome Initiative; ICGC Breast Cancer Consortium; ICGC MMML-Seq Consortium; ICGC PedBrain; Zucman-Rossi J, Futreal PA, McDermott U, Lichter P, Meyerson M, Grimmond SM, Siebert R, Campo E, Shibata T, Pfister SM, Campbell PJ, Stratton MR. Signatures of mutational processes in human cancer. Nature. 2013 Aug 22;500(7463):415-21. doi: 10.1038/nature12477. Epub 2013 Aug 14.
• Background Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003 Jan 16;348(3):203-13. doi: 10.1056/NEJMoa020177.
• Background Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan M, Conejo-Garcia JR, Zhang L, Burow M, Zhu Y, Wei S, Kryczek I, Daniel B, Gordon A, Myers L, Lackner A, Disis ML, Knutson KL, Chen L, Zou W. Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med. 2004 Sep;10(9):942-9. doi: 10.1038/nm1093. Epub 2004 Aug 22.
• 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 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 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 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 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 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 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 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 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 Waight JD, Chand D, Dietrich S, Gombos R, Horn T, Gonzalez AM, Manrique M, Swiech L, Morin B, Brittsan C, Tanne A, Akpeng B, Croker BA, Buell JS, Stein R, Savitsky DA, Wilson NS. Selective FcgammaR Co-engagement on APCs Modulates the Activity of Therapeutic Antibodies Targeting T Cell Antigens. Cancer Cell. 2018 Jun 11;33(6):1033-1047.e5. doi: 10.1016/j.ccell.2018.05.005.
• 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 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 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 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 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 Colombo N, Van Gorp T, Matulonis UA, Oaknin A, Grisham RN, Fleming GF, Olawaiye AB, Nguyen DD, Greenstein AE, Custodio JM, Pashova HI, Tudor IC, Lorusso D. Relacorilant + Nab-Paclitaxel in Patients With Recurrent, Platinum-Resistant Ovarian Cancer: A Three-Arm, Randomized, Controlled, Open-Label Phase II Study. J Clin Oncol. 2023 Oct 20;41(30):4779-4789. doi: 10.1200/JCO.22.02624. Epub 2023 Jun 26.
• 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 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 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 Peixoto AJ. Acute Severe Hypertension. N Engl J Med. 2019 Nov 7;381(19):1843-1852. doi: 10.1056/NEJMcp1901117. No abstract available.
• Background Sharma P, Nagarajan V. Q: Can an ARB be given to patients who have had angioedema on an ACE inhibitor? Cleve Clin J Med. 2013 Dec;80(12):755-7. doi: 10.3949/ccjm.80a.13041. No abstract available.

Drugs

Indications