The Effect of Isoquercetin on Thromboembolic Events in Patients with Metastatic Pancreatic Cancer

The aim of this Phase 3 study is to evaluate the efficacy of isoquercetin as compared to the placebo in prevention of thromboembolic events in patients with metastatic pancreatic cancer.

Approximately one-third of all pancreatic cancer patients suffer from a venous thromboembolism (VTE). The greatest risk of thrombosis is observed in the first three months following the start of chemotherapy. The development of distant metastasis in pancreatic cancer increases the risk of VTE approximately 4-fold.

Isoquercetin is a more bioavailable form of quercetin, a naturally occurring flavonol, intended to prevent thromboembolic events in cancer patients. The aim of this study is to evaluate the efficacy of isoquercetin in prevention of thromboembolic events in patients with metastatic pancreatic cancer.

This trial is a randomized, placebo-controlled, double-blinded, Phase 3 trial in metastatic pancreatic cancer patients who are initiating chemotherapy.

Eligibility Criteria:
Inclusion Criteria:

1. Participants must have histological or cytological confirmed advanced pancreatic adenocarcinoma malignancy that is metastatic (including recurrent with distant metastases)
2. Receiving first line chemotherapy (within 30 days of first dose of study drug) Note: subjects must be either initiating first systemic cancer therapy regimen following initial diagnosis or initiating first cycle of chemotherapy for disease recurrence
3. Minimum age 18 years
4. Life expectancy of greater than 6 months
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. Participants must have preserved organ and marrow function as defined by:

   * Platelet count ≥ 50,000/mcL
   * Prothrombin time (PT) and partial thromboplastin time (PTT) ≤ 1.5x institutional upper limit of normal (ULN)
   * Total bilirubin ≤ 3x ULN without liver metastases and \< 5x ULN in presence of liver metastases
   * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3x ULN without liver metastases and \< 5x ULN in the presence of liver metastases
   * Estimated creatinine clearance (CrCl \> 30 mL/min)
7. 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
8. Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

1. Participants with known brain metastases
2. Prior history of documented thromboembolic event within the last 2 years (excluding central line associated events whereby patients completed anticoagulation)
3. Active bleeding or high risk for bleeding (e.g. known acute gastrointestinal ulcer)
4. History of significant hemorrhage (requiring hospitalization or transfusion) outside of a surgical setting within the last 24 months
5. Familial bleeding diathesis
6. Known diagnosis of disseminated intravascular coagulation (DIC)
7. Currently receiving anticoagulant therapy
8. Current daily use of aspirin (\> 81mg daily), 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 \> 800mg daily or equivalent)
9. 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
10. Known intolerance of (iso)quercetin, niacin, or ascorbic acid (including known G6PD deficiency)
11. Females of child-bearing potential must be non-lactating, must have a negative pregnancy test at Screening, and must agree to continue using contraception throughout the study and for 4 weeks after study completion
12. Participation in other clinical trials