Cancer Associated Thrombosis and Isoquercetin (CAT IQ) (CAT IQ)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Thromboembolism of Vein VTE in Colorectal Cancer; Thromboembolism of Vein in Pancreatic Cancer; Thromboembolism of Vein in Non-small Cell Lung Cancer	Drug: Isoquercetin	Phase 2; Phase 3

Detailed Description:

• This research study is a Phase II/III clinical trial.

  --The goal of this trial is to evaluate if isoquercetin can prevent blood clots in patients with pancreas, non small cell lung cancer or colorectal cancer. In the Phase II part of this study, the investigators are looking for the dose of isoquercetin to reduce D-dimer and demonstrate safety.

• Phase III Endpoint and Treatment Plan

  • Primary Endpoint for Phase III portion of protocol: Cumulative incidence of VTE.
  • Following the completion of the phase II portion, enrolled patients will be randomized 1:1 to Arm C (isoquercetin) or Arm D (placebo). The dose for Arm C will be determined after evaluation of the Phase II portion of the trial. The protocol will be amended when the decision is made whether to proceed to Phase III and what dose to use for Arm C. The study will be double-blinded to treatment arm. 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.
  • At BIDMC, optional blood draw will be performed at time 0 and 4 hours following the first dose of study drug.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	618 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomized, Placebo-controlled, Double-blind Phase II/III Trial of Oral Isoquercetin to Prevent Venous Thromboembolic Events in Cancer Patients.
Study Start Date :	January 2015
Estimated Primary Completion Date :	August 2018
Estimated Study Completion Date :	April 2023

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Isoquercetin; Isoquercetin: Cohort A: 500 mg, Once daily, 28 days or 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; Other Names: quercetin-3-O-glucoside; 482-35-9

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants with Reduced D-dimer values [ Time Frame: Baseline, 56 Day ]
   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.
2. Safety [ Time Frame: study visits until day 56 ]
   Will evaluate toxicity of isoquercetin

Secondary Outcome Measures :

1. Cumulative Incidence of VTE at 56 days [ Time Frame: 56 days ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• 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
  • 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 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:

• 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.

Contacts and Locations

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Contacts

Contact: Jeffrey Zwicker, MD	617-667-9299	jzwicker@bidmc.harvard.edu

Locations

United States, California
USC/Norris Comprehensive Cancer Center	Recruiting
Los Angeles, California, United States, 90033
Contact: Howard Liebman, MD 323-865-0579 Liebman_h@med.usc.edu
Principal Investigator: Howard Liebman, MD
VA Northern California Health Care System	Recruiting
Sacramento, California, United States, 95655
Contact: Theodore Wun, MD 916-734-1507 Twun@ucdavis.edu
Principal Investigator: Theodore Wun, MD
United States, Connecticut
VA Connecticut Healthcare System	Recruiting
West Haven, Connecticut, United States, 06450
Contact: Ellice Wong, MD 203-937-3421 Ellice.wong@va.gov
Principal Investigator: Ellice Wong, MD
United States, District of Columbia
Veterans Affair Medical Center	Recruiting
Washington, District of Columbia, United States, 20422
Contact: Anita Aggarwal, DO, PhD 202-745-8000 anita.aggarwal@va.gov
Principal Investigator: Anita Aggarwal, DO, PhD
United States, Maine
York Hospital-Oncology Treatment Center	Recruiting
York, Maine, United States, 03909
Contact: Marilyn D. McLaughlin, MD 207-351-3777 Mmclaughlin@yorkhospital.com
Principal Investigator: Marilyn D. McLaughlin, MD
United States, Massachusetts
Boston VA Healthcare System	Recruiting
Boston, Massachusetts, United States, 02130
Contact: Kenneth Bauer, MD 857-364-5033 kenneth.bauer@va.gov
Principal Investigator: Kenneth A. Bauer, MD
Beth Israel Deaconess Medical Center	Recruiting
Boston, Massachusetts, United States, 02215
Contact: Jeffrey Zwicker, MD 617-667-9299 jzwicker@bidmc.harvard.edu
Principal Investigator: Jeffrey Zwicker, MD
Mount Auburn Hospital	Recruiting
Waltham, Massachusetts, United States, 02138
Contact: Thomas Caughey, MD 617-497-9646 tcaughey@mah.harvard.edu
Principal Investigator: Thomas Caughey, MD
United States, Missouri
Washington University in St. Louis	Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Kristen Sanfilippo, MD 314-362-0233 ksanfilippo@wustl.edu
Principal Investigator: Kristen Sanfilippo, MD
United States, Rhode Island
Providence VA Medical Center	Recruiting
Providence, Rhode Island, United States, 02908
Contact: Katherine Faricy-Anderson, MD 401-732-7100 ext 6158 Katherine.faricy-anderson@va.gov
Principal Investigator: Katherine Faricy-Anderson, MD
United States, Vermont
White River Junction VA Medical Center	Recruiting
White River Junction, Vermont, United States, 05009
Contact: Nancy Kuemmerle, DO, PhD 802-295-9363 Nancy.Kuemmerle@va.gov
Principal Investigator: Nancy Kuemmerle, DO, PhD

Sponsors and Collaborators

Jeffrey Zwicker, MD

Quercegen Pharmaceuticals

National Heart, Lung, and Blood Institute (NHLBI)

Investigators

Principal Investigator:	Jeffrey Zwicker, MD	Beth Israel Deaconess Medical Center

More Information

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Responsible Party:	Jeffrey Zwicker, MD, Principal Investigator, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:	NCT02195232 History of Changes
Other Study ID Numbers:	14-114
First Posted:	July 21, 2014
Last Update Posted:	May 17, 2018
Last Verified:	May 2018

Keywords provided by Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center:

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

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Pancreatic Neoplasms; Thromboembolism; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms	Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases