Isoquercetin for people with ovarian cancer

Randomized, Multi-dose, Placebo-controlled Phase 2 Trial of Oral Isoquercetin to Reduce Thrombin Generation in Ovarian Cancer

This trial will test whether taking isoquercetin along with first-line chemotherapy can lower blood markers tied to blood clot risk in people with ovarian cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 90 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Memorial Sloan Kettering Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 8 sites (Boston, Massachusetts and 7 other locations)
• Trial ID: NCT07303894 on ClinicalTrials.gov

What this trial studies

This Phase 2 randomized, placebo-controlled trial gives isoquercetin or a matching placebo to adults with histologically confirmed epithelial, serous, or clear cell ovarian cancer who are starting first-line chemotherapy. Treatment is started on day 1 of cycle 1 or 2 of chemotherapy and participants have serial blood tests to measure biomarkers linked to clotting risk. The main comparison is the change in those blood markers between the isoquercetin and placebo groups over the treatment period. The trial is led by Memorial Sloan Kettering Cancer Center with additional data collection at Beth Israel Deaconess.

Who should consider this trial

Good fit: Ideal candidates are adults (≥18) with confirmed epithelial, serous, or clear cell ovarian cancer who are starting first-line neoadjuvant, adjuvant, or advanced chemotherapy, have ECOG performance status <2, life expectancy >6 months, and adequate organ and marrow function.

Not a fit: Patients not starting first-line chemotherapy, those with poor performance status or inadequate organ function, or those with very limited life expectancy are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, isoquercetin could lower biomarkers associated with venous blood clots and potentially reduce clot risk during chemotherapy.

How similar studies have performed: Preclinical studies and small early-phase human studies suggest isoquercetin can affect platelet function and clotting biomarkers, but randomized evidence in ovarian cancer is limited.

Eligibility criteria

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.
* ECOG performance status \<2
* Participants must have preserved organ and marrow function as defined below:

  * 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 non-steroidal 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.

Where this trial is running

Boston, Massachusetts and 7 other locations

• Beth Israel Deaconess Medical Center (Data Collection Only) — Boston, Massachusetts, United States (Not_yet_recruiting)
• Memorial Sloan Kettering Basking Ridge (All Protocol Activities) — Basking Ridge, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Monmouth (All Protocol Activities) — Middletown, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Bergen (All Protocol Activities) — Montvale, New Jersey, United States (Recruiting)
• Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities ) — Commack, New York, United States (Recruiting)
• Memorial Sloan Kettering Westchester (All Protocol Activities) — Harrison, New York, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center (All Protocol Activites) — New York, New York, United States (Recruiting)
• Memorial Sloan Kettering Nassau (All protocol activities) — Rockville Centre, New York, United States (Recruiting)

Study contacts

• Principal investigator: Jeffrey Zwicker, MD — Memorial Sloan Kettering Cancer Center
• Study coordinator: Jeffrey Zwicker, MD

Conditions Ovarian Cancer; Epithelial Ovarian Cancer; Serous Ovarian Tumor; Isoquercetin; Memorial Sloan Kettering Cancer Center; 25-060