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

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.

Inclusion criteria

• ≥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.

Exclusion criteria

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