Telmisartan with standard chemotherapy for platinum-resistant ovarian cancer

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

This test will see if adding telmisartan to standard chemotherapy helps people with platinum-resistant high-grade serous ovarian cancer live longer without their disease getting worse.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 33 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Dartmouth-Hitchcock Medical Center (Academic / other)
• Drugs / interventions: rituximab, bevacizumab, chemotherapy
• Locations: 2 sites (Lebanon, New Hampshire and 1 other locations)
• Trial ID: NCT06815497 on ClinicalTrials.gov

What this trial studies

This open-label, single-arm Phase II trial gives telmisartan together with selected standard-of-care chemotherapy regimens that include an anthracycline or a taxane to adults with platinum-resistant high-grade serous ovarian cancer. The primary endpoint is progression-free survival compared against historical controls. Eligible participants must have ECOG performance status 0–2, adequate organ and bone marrow function, and be able to receive the allowable chemotherapy regimens. The study is conducted at Dartmouth-Hitchcock sites in New Hampshire.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed high-grade serous ovarian carcinoma that is platinum-resistant or refractory, ECOG 0–2, adequate organ and bone marrow function, and able to receive anthracycline- or taxane-containing standard chemotherapy are ideal candidates.

Not a fit: Patients with non-serous ovarian cancer histology, platinum-sensitive disease, poor organ or bone marrow function, ECOG >2, or those unable to receive the allowed chemotherapies or attend the Dartmouth-Hitchcock sites are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could prolong progression-free survival and delay the need for additional therapies.

How similar studies have performed: Clinical evidence for angiotensin receptor blockers like telmisartan in ovarian cancer is limited, with mainly preclinical data and small early-phase reports suggesting potential anti-tumor effects but no large confirmatory trials.

Eligibility criteria

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

Where this trial is running

Lebanon, New Hampshire and 1 other locations

• Dartmouth Hitchcock — Lebanon, New Hampshire, United States (Recruiting)
• Dartmouth-Hitchcock Manchester — Manchester, New Hampshire, United States (Recruiting)

Study contacts

• Principal investigator: Ivy Wilkinson-Ryan, MD — Dartmouth Health
• Study coordinator: Kayla Fay

Conditions Ovarian Cancer