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A Study of Isoquercetin for Reducing Blood Clot Formation Risk in Patients With Ovarian Cancer
Trial Status: active
This phase II trial tests how well giving isoquercetin works to reduce markers in the blood that may indicate the risk of blood clots for patients with ovarian cancer. People who have ovarian cancer have a high risk of developing a medical condition called venous thromboembolism (VTE). A VTE is a blood clot (thrombus) that has formed in a vein. It can move anywhere in the body and block blood flow. A piece of the clot may break loose. This is called an embolus. The embolus can travel to the lungs and cause a life-threatening clot called a pulmonary embolism. Isoquercetin is part of a class of drugs called flavonoids, which naturally occur in plants to control enzyme activity, provide coloring, improve defense, and filter ultraviolet light. Flavonoids can be found in many fruits and vegetables. Isoquercetin blocks an enzyme called protein disulfide isomerase (PDI), which contributes to the formation of blood clots. Enzymes help speed up chemical reactions in the body and help with many cell functions, including cell signaling, growth, and division. Giving isoquercetin may work well to block the PDI enzyme and lower the risk of blood clots for patients with ovarian cancer.
Inclusion Criteria
Participants must have histological- or cytological-confirmed ovarian cancer (epithelial, serous, or clear cell) and be receiving first-line chemotherapy (day 1 of isoquercetin should align with day 1 of cycle 1 or 2 of chemotherapy) for neoadjuvant, adjuvant, or advanced settings
Minimum age 18 years
Life expectancy of greater than 6 months
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
Platelet count ≥ 50,000/mcL
Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5 x institutional upper limit of normal (ULN)
Total bilirubin ≤ 3 x ULN without liver metastases and < 5 x ULN in presence of liver metastases
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 X ULN without liver metastases and < 5 x ULN in the presence of liver metastases
Estimated creatinine clearance (CrCl > 30 ml/min)
The effects of isoquercetin on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
Ability to understand and the willingness to sign a written informed consent document
Exclusion Criteria
Prior history of documented venous thromboembolic event within the last 2 years (excluding central line associated events whereby patients completed anticoagulation)
Active bleeding or high risk for bleeding (e.g., known acute gastrointestinal ulcer)
History of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last 24 months
Familial bleeding diathesis
Known diagnosis of disseminated intravascular coagulation (DIC)
Currently receiving anticoagulant therapy
Current daily use of aspirin, clopidogrel (Plavix), cilostazol (Pletal), aspirin-dipyridamole (Aggrenox) (within 10 days) or considered to use regular use of higher doses of nonsteroidal anti-inflammatory agents as determined by the treating physician (e.g ibuprofen > 800 mg daily or equivalent)
Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Known intolerance of (iso)quercetin, niacin or ascorbic acid (including known G6PD deficiency)
Participants with known brain metastases
Pregnant women are excluded from this study because isoquercetin is a PDI inhibitor with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk of adverse events in nursing infants secondary to treatment of the mother with isoquercetin, breastfeeding should be discontinued if the mother is treated with isoquercetin
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT07303894.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Jeffrey Isaac Zwicker
Phone: 646-608-3723
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Jeffrey Isaac Zwicker
Phone: 646-608-3723
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Jeffrey Isaac Zwicker
Phone: 646-608-3723
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Jeffrey Isaac Zwicker
Phone: 646-608-3723
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Jeffrey Isaac Zwicker
Phone: 646-608-3723
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Jeffrey Isaac Zwicker
Phone: 646-608-3723
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Jeffrey Isaac Zwicker
Phone: 646-608-3723
PRIMARY OBJECTIVE:
I. To compare maximal inhibition of platelet-dependent thrombin generation (relative to baseline) between the 3 arms.
SECONDARY OBJECTIVES:
I. To summarize platelet-dependent thrombin generation activity in plasma following isoquercetin administration as measured by cell-based and enzymatic assays.
II. To summarize PDI inhibitory activity in plasma following isoquercetin administration as measured by cell-based and enzymatic assays.
III. To evaluate the safety of isoquercetin administration as assessed by incidence of major hemorrhage.
EXPLORATORY OBJECTIVES:
I. To estimate correlation between plasma quercetin metabolomics and PDI inhibition at different timepoints.
II. To estimate cumulative incidence of venous thromboembolism (VTE) at 6 weeks in each arm.
III. To estimate cumulative incidence of clinically relevant or major hemorrhage at 6 weeks in each arm.
IV. To identify a phenotype that is likely to be more or less responsive to PDI inhibition with isoquercetin, including biomarkers indicative of endoplasmic reticulum (ER) stress (i.e., protein disulfide isomerase [PDI] and GRP78), CD200R1-mediated tumor immune response (i.e., CD200R1 and IL-17a), and neutrophil extracellular traps (NETS) (i.e., cell-free deoxyribonucleic acid [cfDNA] and citrullinated histone H3 [H3Cit]).
OUTLINE: Patients are randomized to 1 of 3 cohorts.
COHORT A: Patients receive placebo orally (PO) twice daily (BID) on days 1-21 of each cycle. Cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
COHORT B: Patients receive isoquercetin PO twice once daily (QD) in the morning and placebo PO QD in the evening on days 1-21 of each cycle. Cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
COHORT C: Patients receive isoquercetin PO BID on days 1-21 of each cycle. Cycles repeat every 21 days for 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 30 days.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
