Cancer Associated Thrombosis and Isoquercetin (CATIQ)

Inclusion Criteria:

• Participants must meet the following criteria on screening examination to be eligibleto participate in phase 2 and 3 of the study:
• Participants must have histologically confirmed malignancy that is metastatic orcurrently unresectable.
• Eligible malignancies include:
• Adenocarcinoma of the pancreas (currently unresectable or metastatic)
• Colorectal (stage IV)
• Non-small cell lung cancer (currently unresectable stage III or stage IV)
• Receiving or scheduled to receive first or second line chemotherapy (within 30 days ofregistration)
• Minimum age 18 years. Because limited dosing or adverse event data are currentlyavailable on the use of isoquercetin in participants <18 years of age, children areexcluded from this study but will be eligible for future pediatric isoquercetintrials.
• Life expectancy of greater than 4 months.
• ECOG performance status ≤2 (see Appendix B ).
• Patient must be able to swallow capsules (phase III only)
• Participants must have preserved organ and marrow function as defined below:
• Absolute neutrophil count ≥1,000/mcL
• Platelets ≥ 90,000/mcL
• PT and PTT ≤ 1.5 x upper limit of normal
• Total bilirubin < 2.0 mg/dl
• AST (SGOT)/ALT (SGPT) ≤ 2.5 X institutional upper limit of normal Creatinine < 2.0 mg/dl
• The effects of isoquercetin on the developing human fetus are unknown. For thisreason, women of child-bearing potential and men must agree to use adequatecontraception (hormonal or barrier method of birth control; abstinence) prior to studyentry and for the duration of study participation. Should a woman become pregnant orsuspect she is pregnant while participating in this study, she should inform hertreating physician immediately.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Participants may not be receiving any other study agents.
• Participants with known brain metastases should be excluded from this clinical trialbecause of their poor prognosis and because they often develop progressive neurologicdysfunction that would confound the evaluation of neurologic and other adverse events.
• 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) outsideof 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 (>81mg daily), Clopidogrel (Plavix), cilostazol (Pletal),aspirin-dipyridamole (Aggrenox) (within 10 days) or considered to use regular use ofhigher doses of non-steroidal anti-inflammatory agents as determined by the treatingphysician (e.g ibuprofen > 800 mg daily or equivalent).
• Uncontrolled intercurrent illness including, but not limited to ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, cardiacarrhythmia, or psychiatric illness/social situations that would limit compliance withstudy requirements.
• Known intolerance of niacin or ascorbic acid (including known G6PD deficiency)
• Pregnant women are excluded from this study because isoquercetin is a PDI inhibitorwith the potential for teratogenic or abortifacient effects. Because there is anunknown but potential risk of adverse events in nursing infants secondary to treatmentof the mother with isoquercetin, breastfeeding should be discontinued if the mother istreated with isoquercetin. These potential risks may also apply to other agents usedin this study.