Telmisartan in Prostate Cancer

Официальное название

Phase I Non-Randomized, Unblinded, Single-Center Trial of Oral Telmisartan Alone or Combined With Selected Standard of Care Therapies for Prostate Cancer

Обзор

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.

Подробное описание

The primary objective of this study is to test the tolerability of oral telmisartan given as a single agent or combined with specific standard of care agents in selected participants with PC. Patients will be defined as tolerating telmisartan if they maintain systolic blood pressure \>110 mm Hg and are without greater than grade 2 toxicities as defined in the Common Terminology Criteria for Adverse Events v5.1 for at least 60 days total telmisartan treatment.

Вмешательства

• Препарат Telmisartan
  Patients will be given telmisartan alone or with standard of care chemotherapy.
• Другое Standard of Care Regimen
  Standard of Care Regimen

Первичные конечные точки

• Tolerability of oral telmisartan [Срок оценки: 12 months]

Вторичные конечные точки (1)

• Increase in tumor DNA damage [Срок оценки: 24 months]

Критерии участия

Критерии включения

• Participants must be ≥18 years of age.
• Participants must be able and willing to provide informed consent or have a surrogate capable of providing same.
• Participants must not require immediate change in SOC treatment, i.e., patients with stable PSA (do not meet PCWG310 criteria for PSA progression), or with rising PSA but they remain on SOC treatment (defined as having met PCWG3 criteria for PSA progression, but do not have clinical/radiographic progression and have not met criteria for an immediate change in therapy based on PSA doubling time) as determined by their primary oncologist
• Participants must be receiving or likely to receive one of the following SOC agents for PC:

cabazitaxel, docetaxel (alone or plus abiraterone) olaparib, rucaparib, or talazoparib plus enzalutamide

• Participants must have
• ECOG performance status of 0-2
• Adequate hepatic (SCOT ≤3x ULN) and renal function (serum creatinine ≤2.5 or estimated GFR >30 cc/min)
• Standing systolic blood pressure >/= 110mm Hg
• If not on active surveillance, patient mut have castrate level testosterone
• No contraindication to telmisartan, including ACE inhibitor use in the 6 weeks prior to projected telmisartan start on trial
• All participants must have a systolic blood pressure >110 mm Hg during study enrollment assessment and throughout the study
• If participants are concurrently treated for hypertension, they must be able to allow telmisartan in addition to, or replacing their antihypertensive regimen
• Participants must be able to withstand planned research phlebotomies (Hb >10 gm/dl).
• Participants must have a blood prostate specific antigen > 1 ng/ml at study entry using the Roche Cobas immunoassay.
• Participants must be able to take or have taken their own blood pressure per the study protocol (daily during telmisartan escalation and for two weeks after the final escalation and weekly thereafter for the following month and then monthly) if normotensive at enrollment.

Критерии исключения

Participants who fall into one of the following categories will NOT be eligible for this study:

• Angiotensin l receptor blocker use currently or within the 30 days prior to day 1, cycle 1.
• Patients with hypertensive urgency or emergency as defined in N Engl J Med. 2019 Nov 7;381(19):1843-1852. doi:10.1056/NEJMep1901117
• Patients who are incarcerated or homeless
• Patients who are receiving PC-specific treatment aside from cabazitaxel, docetaxel, olaparib, rucaparib, abiraterone or talazoparib plus enzalutamide or have plans to undergo the same during the study period, except local irradiation therapy to PC lesions.
• Patients on lithium therapy in any form
• Patients who received rituximab or amifostine within 30 days prior to first telmisartan dose on this study
• Patients on ramapril
• Patients on digoxin who do not consent to monthly digoxin blood level testing

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• Dartmouth Health — Lebanon

Публикации

• 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
• 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.e PMID 28314611
• 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. PMID 36509970
• 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. PMID 34473525
• 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 p PMID 28851861
• 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, phas PMID 37714168
• 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
• 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

Идентификаторы

NCT: NCT06168487 · STUDY02002057 · NCI-2024-07041

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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