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

Официальное название

Phase II Non-Randomized, Unblinded, Single-Center Trial of Telmisartan in Combination With Cytotoxic Regimens in Platinum-Resistant Ovarian Cancer Versus Historical Best Supportive Care

Обзор

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.

Подробное описание

This is an open label, single-arm Phase II trial of telmisartan plus selected standard of care chemotherapy regimens containing an anthracycline or taxane. The primary study objective is to assess progression-free survival.

Вмешательства

• Препарат Telmisartan
  Telmisartan will be introduced as a 40 mg tablet to be taken orally once daily. In participants not experiencing telmisartan dose limiting toxicity, the dose will be escalated to a maximum of 80 mg

Первичные конечные точки

• Progression free survival [Срок оценки: 48 months]

Вторичные конечные точки (2)

• Treatment tolerability [Срок оценки: 24 months]
• Circulating tumor DNA changes [Срок оценки: 24 months]

Критерии участия

Критерии включения

• ≥18 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Able and willing to provide informed consent.
• Histologically proven high-grade serous ovarian carcinomas (HGSOC)
• Platinum-resistant or refractory ovarian cancer (OC) defined as progression of disease on carboplatin or growth of disease as detected on computed tomography (CT) scan within 6 months of last platinum treatment
• To receive the allowable standard of care (SOC) chemotherapy regimens for OC
• Life expectancy ≥2 months
• Adequate organ and bone marrow reserve function as indicated by the following:
• Adequate hematological function, defined as absolute neutrophil count (ANC) ≥1.5 x 10\^9/L, platelet count ≥100 x 10\^9/L, and hemoglobin ≥8 g/dL without recent transfusion (defined as a transfusion that has occurred within 2 weeks of the hemoglobin measurement)
• Adequate liver function, defined as total bilirubin level ≥1.5 x institutional upper limit of normal (IULN), aspartate aminotransferase (AST) ≤ 2.5 x IULN, and alanine aminotransferase (ALT) ≤ 2.5 x IULN
• Adequate renal function defined as creatinine ≤ 1.5 x IULN or measured or calculated creatinine clearance ≥ 40 mL/min per institutional standard. Assessment methods must be recorded.
• Adequate coagulation, defined as international normalized ratio (INR) or prothrombin time ≤ 1.5 x IULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x IULN (unless patient receiving anticoagulant therapy).
• Female patients of childbearing potential (FCBP) must agree to use highly effective contraceptive method(s) while on this study and for at least 3 months after the last dose of chemotherapy
• FCBP must have a negative serum pregnancy test at screening (within 72 hours of first dose of study medication). Non-childbearing potential is defined as 1 of the following:
• ≥ 45 years of age and has not had menses for >1 year
• Amenorrheic for > 2 years without a hysterectomy and/or oophorectomy and follicle stimulating hormone value in the postmenopausal range upon pretrial (screening) evaluation
• Status is post-hysterectomy, -oophorectomy, or -tubal ligation
• Genetic defect precluding pregnancy
• No contraindication to telmisartan\*, including angiotensin converting enzyme (ACE) inhibitor use in the 6 weeks prior to telmisartan start on trial
• Systolic blood pressure maintained at ≥ 110 mm Hg during study enrollment assessment and throughout the study.

Критерии исключения

Patients who meet any of the criteria below may NOT be eligible to participate in this study:

• Patients who are unable to provide informed consent.
• Patients with known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; and cirrhosis. For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they must have an undetectable HCV viral load
• Hypertensive urgency or emergency as defined
• Incarcerated or homeless
• Pregnant or lactating.
• Individuals who are not yet adults <18 years of age.
• On lithium therapy in any form
• Received rituximab or amifostine within 30 days prior to first telmisartan dose on this study
• Active, serious infection requiring treatment
• Clinically significant (i.e., active) cardiovascular disease, cerebral vascular accident/stroke or myocardial infarction within 6 months of enrollment, unstable angina, congestive heart failure (New York Heart Association class ≥II), or serious uncontrolled cardiac arrhythmia requiring medication
• History or current evidence of any condition, therapy, and active infections, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator
• Taking ramapril
• Using bevacizumab as part of their SOC chemotherapy regimen
• If known to be HIV-infected, have undetectable HIV viral load by any accepted standard of care HIV detection method

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Dartmouth Hitchcock — Lebanon
• Dartmouth-Hitchcock Manchester — Manchester

Публикации

• 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. PMID 37079311
• 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 Gyn PMID 38055253
• 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. PMID 37820582
• 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. PMID 25648541
• 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. PMID 32617007
• 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. PMID 36691778
• 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, North PMID 23945592
• 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. PMID 12529460

Идентификаторы

NCT: NCT06815497 · STUDY02002599 · 24WIL599

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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