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

Phase 3

Not yet recruiting

• Conditions: Venous Thromboembolism; Metastatic Pancreatic Cancer
• Interventions: Drug: Isoquercetin; Drug: Placebo

• Registration Number: NCT06861088
• Lead Sponsor: Quercis Pharma AG

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2025-02
• Study First Submitted: 2025-02-28
• Study First Submitted QC: 2025-03-05
• Last Update Submitted: 2025-03-05
• Study First Posted: 2025-03-06
• Last Update Posted: 2025-03-06
• Study Start: 2025-06-30
• Primary Completion: 2026-07-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 340

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Isoquercetin 1000mg	Isoquercetin	Initially, patients will be randomized on a 1:1:1 basis to Isoquercetin 1000mg, Isoquercetin 2000mg or matching placebo daily. Patients in this group will be administered Isoquercetin at a daily dose of 1000mg (orally at 8 capsules per day for 16 weeks). An interim analysis will be performed when 26 primary endpoint events have been attained across all three arms and the best performing dose will be identified and a sample size reassessment performed. Thereafter, randomization to the study will continue only for the selected dose and placebo on a 1:1 basis.
Isoquercetin 2000mg	Isoquercetin	Initially, patients will be randomized on a 1:1:1 basis to Isoquercetin 1000mg, Isoquercetin 2000mg or matching placebo daily. Patients in this group will be administered Isoquercetin at a daily dose of 2000mg (orally at 8 capsules per day for 16 weeks). An interim analysis will be performed when 26 primary endpoint events have been attained across all three arms and the best performing dose will be identified and a sample size reassessment performed. Thereafter, randomization to the study will continue only for the selected dose and placebo on a 1:1 basis.
Placebo	Placebo	Patients in this group will be administered placebo orally at 8 capsules per day for 16 weeks (4 capsules in the morning and 4 capsules in the evening).

Primary Outcome Measures

Name	Time	Method
Effectiveness of Isoquercetin	16 weeks	The composite endpoint includes any proximal or distal lower extremity DVT, any pulmonary embolism, fatal pulmonary embolism diagnosed on autopsy, catheter-related thrombosis, visceral thrombosis or arterial thrombosis. Events will be classified as incidental or symptomatic: incidental TE will be so classified if the imaging was ordered primarily for staging or re-staging or conducted for reasons other than identification of a thrombosis as compared to the placebo.

Secondary Outcome Measures

Name	Time	Method
To assess the risk of TE defined as proximal or distal lower extremity DVT, any pulmonary embolism, fatal pulmonary embolism diagnosed on autopsy, or arterial thrombosis	16 weeks	To assess the risk of TE defined as proximal or distal lower extremity DVT, any pulmonary embolism, fatal pulmonary embolism diagnosed on autopsy, or arterial thrombosis over 16 weeks post randomization in patients treated with isoquercetin compared with placebo.
To assess the risk of major hemorrhage	16 weeks	To assess the risk of major hemorrhage in patients treated with isoquercetin compared with placebo according to ISTH definition. The criteria for major hemorrhage in non-surgical patients is: * Fatal bleeding, and/or; * Symptomatic bleeding in a critical area or organ such as intracranial, intraspinal, intraocular, retroperitoneal, intra-articular or pericardial, or intramuscular with compartment syndrome, and/or; * Bleeding causing a fall in hemoglobin level ≥ 2 g/L or; * Bleeding leading to a transfusion ≥ 2 units of packed red blood cells