Thromboembolism of Vein VTE in Colorectal CancerPhase 2/3CATIQNCT02195232
Cancer Associated Thrombosis and Isoquercetin (CATIQ)
A Phase 2/3 study testing Isoquercetin in people with Thromboembolism of Vein VTE in Colorectal Cancer and Thromboembolism of Vein in Pancreatic Cancer, run by Jeffrey Zwicker, MD at 11 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thromboembolism of Vein VTE in Colorectal Cancer, Thromboembolism of Vein in Pancreatic Cancer, Thromboembolism of Vein in Non-small Cell Lung Cancer
- What is being tested?
- Isoquercetin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 11 sitesUnited States
- Study dates
- Jan 2015to 22 Oct 2019
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
Who cannot join
- 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
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- 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.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
United States11 sites
Boston VA Healthcare System
Boston, Massachusetts, 02130
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
USC/Norris Comprehensive Cancer Center
Los Angeles, California, 90033
Providence VA Medical Center
Providence, Rhode Island, 02908
VA Northern California Health Care System
Sacramento, California, 95655
Washington University in St. Louis
St Louis, Missouri, 63110
Mount Auburn Hospital
Waltham, Massachusetts, 02138
Veterans Affair Medical Center
Washington D.C., District of Columbia, 20422
VA Connecticut Healthcare System
West Haven, Connecticut, 06450
White River Junction VA Medical Center
White River Junction, Vermont, 05009
York Hospital-Oncology Treatment Center
York Village, Maine, 03909
About this study
Official title: Randomized, Placebo-controlled, Double-blind Phase II/III Trial of Oral Isoquercetin to Prevent Venous Thromboembolic Events in Cancer Patients.
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.
Read the 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.
- Conditions
- Thromboembolism of Vein VTE in Colorectal Cancer, Thromboembolism of Vein in Pancreatic Cancer, Thromboembolism of Vein in Non-small Cell Lung Cancer
- Being tested
- Isoquercetin
- 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
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsoquercetinDrug
Also called quercetin-3-O-glucoside, 482-35-9
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Isoquercetin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 56 Day
Secondary outcomes (2)
Number of Participants With Hemorrhage
Investigating the safety of isoquercetin in cancer patients
Measured: study visits until day 56
Cumulative Incidence of VTE at 56 Days
To investigate the cumulative incidence of VTE according to tissue factor bearing microparticle status (and isoquercetin randomization).
Measured: 56 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2014 (estimated)
- Study startJan 2015
- Primary completionDec 2018
- Study completion22 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thromboembolism of Vein VTE in Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jeffrey Zwicker, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Quercegen Pharmaceuticals, National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Jeffrey Zwicker, MD, Beth Israel Deaconess Medical Center
- Investigators
- Jeffrey Zwicker, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02195232
- Sponsor's protocol ID
- 14-114
- Acronym
- CATIQ
- Status last verified
- Feb 2021
- First submitted
- 13 May 2014
- Last updated
- 3 Mar 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 30652973
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Placebo-controlled, Double-blind Phase II/III Trial of Oral Isoquercetin to Prevent Venous Thromboembolic Events in Cancer Patients.
- ClinicalTrials.gov ID
- NCT02195232
- Acronym / sponsor ID
- CATIQ / 14-114
- 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
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Jeffrey Zwicker, MDUniversity, hospital or other
- Collaborators
- Quercegen Pharmaceuticals, National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Jan 2015 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- 22 Oct 2019 (actual)
- First posted
- 21 Jul 2014 (estimated)
- Results
- Posted 12 Nov 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A - Isoquercetin | Experimental | Drug: Isoquercetin-- 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. |
| Cohort B - Isoquercetin | Experimental | Drug: Isoquercetin--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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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:
- 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.
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IsoquercetinAlso: quercetin-3-O-glucoside, 482-35-9 | Drug | Cohort A - Isoquercetin, Cohort B - Isoquercetin |
Primary outcome
Percent Change in D-dimer Value
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 secondary outcomes
Number of Participants With Hemorrhage
Time frame: study visits until day 56
Cumulative Incidence of VTE at 56 Days
Time frame: 56 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30652973Zwicker 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.
Related trials for Thromboembolism of Vein VTE in Colorectal Cancer
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Zwicker, MD principal investigator
Beth Israel Deaconess Medical Center
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Isoquercetin in people with Thromboembolism of Vein VTE in Colorectal Cancer and Thromboembolism of Vein in Pancreatic Cancer, run by Jeffrey Zwicker, MD at 11 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Nov 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in D-dimer Value (time frame: Baseline, 56 Day). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02195232, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2021.