Locally Advanced Pancreatic Adenocarcinoma, Metastatic Pancreatic Cancer, Venous Thromboembolism
Conditions
Keywords
Metastatic Pancreatic Cancer, Pancreatic Adenocarcinoma, Thromboembolism, Cancer-associated Thrombosis, Deep Vein Thrombosis, Pulmonary Embolism, Chemotherapy-associated VTE, Locally Advanced Pancreatic Cancer
Brief summary
The aim of this Phase 3 study is to evaluate the efficacy of Kinisoquin™ as compared to the placebo in prevention of thromboembolic events in patients with metastatic or locally advanced 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. Kinisoquin™ 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 Kinisoquin™ in prevention of thromboembolic events in patients with metastatic or locally advanced pancreatic cancer. This trial is a randomized, placebo-controlled, double-blinded, Phase 3 trial in metastatic or locally advanced pancreatic cancer patients who are initiating chemotherapy.
Interventions
DRUGKinisoquin™
Kinisoquin™ capsules formulated with vitamin C and vitamin B3
DRUGPlacebo
Placebo
Sponsors
Quercis Pharma AG
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Intervention model description
Initially, patients will be randomized on a 1:1:1 basis to Kinisoquin™ 1000 mg, Kinisoquin™ 2000 mg, or matching placebo daily. Kinisoquin™ or placebo will be administered orally at 8 capsules per day for 16 weeks (4 capsules in the morning and 4 capsules in the evening). An interim analysis will be performed when 26 positively adjudicated primary endpoint events have been attained across all three arms, expected to have been accrued after enrolment of the 180th patient. Deselected dose patients will be followed long term for progression-free survival and overall survival but will not be included in the final primary endpoint analysis. Futility will be assessed at the interim and, if passed, the better 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participants must have histological or cytological confirmed pancreatic adenocarcinoma malignancy that is metastatic (including recurrent with distant metastases) or locally advanced. 2. Receiving first line chemotherapy (within 45 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 4 months. 5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 6. Participants must have preserved organ and marrow function as defined by: * Platelet count ≥ 100,000/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. Willingness of women of child-bearing potential and men to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation until at least 4 weeks after study completion. 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 12 months (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 (\> 100mg 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 to the active ingredient of Kinisoquin™, isoquercetin, nicotinic acid, or ascorbic acid (including known G6PD deficiency) 11. Females of child-bearing potential who are lactating, have a positive pregnancy test at Screening, or are unwilling to use acceptable contraception prior to study entry and for the duration of study participation until at least 4 weeks after study completion. 12. Participation in other clinical trials The study is open to any individual who has a metastatic or locally advanced pancreatic adenocarcinoma malignancy without discrimination based on race, religion, political affiliation, or other criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effectiveness of Kinisoquin™ | 16 weeks | The time to the first positively adjudicated thromboembolic event (TE) over 16 weeks of treatment in patients treated with Kinisoquin™ compared with placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Risk of TE | 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 of treatment in patients treated with Kinisoquin™ compared with placebo. |
| Catheter-related TEs | 16 weeks | To assess the risk of catheter-related TEs over 16 weeks after study treatment initiation in patients treated with Kinisoquin™ compared with placebo. |
| Risk of major hemorrhage | 16 weeks | To assess the risk of major hemorrhage in patients treated with Kinisoquin™ 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 |
| Risk of clinically relevant non-major bleeding | 16 weeks | To assess the risk of clinically relevant non-major bleeding in patients treated with Kinisoquin™ compared with placebo. |
| Progression-Free Survival (PFS) | 12 months | Progression-free survival until 12 months after study treatment initiation according to RECIST, as assessed by the site Investigator's review, in patients treated with Kinisoquin™ compared with placebo. |
| Overall Survival (OS) | 24 Months | Overall survival until 24 months after study treatment initiation in patients treated with Kinisoquin™ compared with placebo. |
Countries
United States
Contacts
CONTACTMukesh Kumar, PhD
CONTACTKanisha Shah, MSRA
Outcome results
None listed