Cancer Associated Thrombosis and Isoquercetin (CATIQ)

NCT02195232 | Completed Phase 2 Results DMC

• 1 other identifier: 14-114
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 11

Brief Summary

This research study is evaluating a drug called isoquercetin to prevent venous thrombosis (blood clots), in participants who have pancreas, non small cell lung cancer or colorectal cancer.

Conditions

Thromboembolism of Vein VTE in Colorectal Cancer; Thromboembolism of Vein in Pancreatic Cancer; Thromboembolism of Vein in Non-small Cell Lung Cancer

Keywords

Venous Thromboembolic Events in Cancer Patients; Thromboembolism of Vein in Colorectal Cancer; Thromboembolism of Vein in Pancreatic Cancer; Thromboembolism of Vein in Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Percent Change in D-dimer Value

  D-dimer concentrations will be compared for each patient at day 0 and day 56 by a paired-t test analysis. Analysis will be performed on an intention to treat basis for patients who undergo randomization and completed the baseline and day 56 D-dimer assessments.

  Baseline, 56 Day

Secondary Outcomes (2)

• Number of Participants With Hemorrhage

  study visits until day 56

• Cumulative Incidence of VTE at 56 Days

  56 days

Study Arms (2)

Cohort A - Isoquercetin

EXPERIMENTAL

\-- Cohort A: 500 mg, Once daily, 28 days \- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.

Drug: Isoquercetin

Cohort B - Isoquercetin

EXPERIMENTAL

--Cohort B: 1000 mg, Once daily, 28 days \- For both cohorts A and B, lower extremity ultrasound will be performed at 56 days. Baseline D-dimer and correlative labs will be drawn at Day 1 and at 56 days. Patients will be followed for survival after completion of 56 days.

Drug: Isoquercetin

Interventions

Isoquercetin DRUG

Also known as: quercetin-3-O-glucoside, 482-35-9

Cohort A - Isoquercetin; Cohort B - Isoquercetin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet the following criteria on screening examination to be eligible to participate in phase 2 and 3 of the study:
• Participants must have histologically confirmed malignancy that is metastatic or currently 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 of registration)
• Minimum age 18 years. Because limited dosing or adverse event data are currently available on the use of isoquercetin in participants \<18 years of age, children are excluded from this study but will be eligible for future pediatric isoquercetin trials.
• 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

You may not qualify if:

• Participants may not be receiving any other study agents.
• Participants with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction 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) 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 (\>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 \> 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 niacin or ascorbic acid (including known G6PD deficiency)
• 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. These potential risks may also apply to other agents used in this study.

Sponsors & Collaborators

• Jeffrey Zwicker, MD: lead
• Quercegen Pharmaceuticals: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (11)

USC/Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

VA Northern California Health Care System

Sacramento, California, 95655, United States

Location

VA Connecticut Healthcare System

West Haven, Connecticut, 06450, United States

Location

Veterans Affair Medical Center

Washington D.C., District of Columbia, 20422, United States

Location

York Hospital-Oncology Treatment Center

York Village, Maine, 03909, United States

Location

Boston VA Healthcare System

Boston, Massachusetts, 02130, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Mount Auburn Hospital

Waltham, Massachusetts, 02138, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Providence VA Medical Center

Providence, Rhode Island, 02908, United States

Location

White River Junction VA Medical Center

White River Junction, Vermont, 05009, United States

Location

Related Publications (1)

• Zwicker JI, Schlechter BL, Stopa JD, Liebman HA, Aggarwal A, Puligandla M, Caughey T, Bauer KA, Kuemmerle N, Wong E, Wun T, McLaughlin M, Hidalgo M, Neuberg D, Furie B, Flaumenhaft R; CATIQ Investigators11. Targeting protein disulfide isomerase with the flavonoid isoquercetin to improve hypercoagulability in advanced cancer. JCI Insight. 2019 Feb 21;4(4):e125851. doi: 10.1172/jci.insight.125851. eCollection 2019 Feb 21.

  PMID: 30652973 DERIVED

MeSH Terms

Interventions

isoquercitrin

Results Point of Contact

• Title: Jeffrey Zwicker, Division of Thrombosis and Haemostasis, Division of Hematology and Oncology
• Organization: Beth Israel Deaconess Medical Center, Harvard Medical School

jzwicker@bidmc.harvard.edu

617.667.9299

Study Officials

• Jeffrey Zwicker, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: July 21, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: October 22, 2019
• Last Updated: March 3, 2021
• Results First Posted: November 12, 2019

Record last verified: 2021-02

Locations

US (11)