Study Title:

Cancer Venous Thromboembolism (VTE)

ClinicalTrials.gov Identifier:

Sponsor:

Daiichi Sankyo, Inc.

Study Design:

Randomized, open-label study

Target Enrollment:

1,000 patients

Participating Centers:

Approximately 130 study sites in North America, Europe, and Australia/New Zealand

Accrual Goal:

1,000 patients

Study Synopsis:

This is a multinational, prospective, randomized, open-label, blind-evaluator (PROBE), noninferiority study comparing edoxaban to dalteparin for prevention of the combined outcome of recurrent venous thromboembolism (VTE) or major bleeding in patients with cancer-associated VTE. Eligible patients will have both confirmed deep vein thrombosis (DVT) or pulmonary embolism (PE; symptomatic or unsuspected) as well as active cancer. Key exclusion criteria include: poor performance status, creatinine clearance less than 30 mL/min, life expectancy less than three months, platelet count no higher than 50 x 109/L, or more than 72 hours of therapeutic-dose LMWH prior to randomization. Participants will be treated with either edoxaban 60 mg by mouth daily* versus dalteparin 200 U/kg subcutaneously daily for 30 days (followed by 150 U/kg daily thereafter).

Rationale:

Patients with cancer are at increased risk of VTE, and evidence-based guidelines recommend that cancer-associated VTE be treated with at least six months of LMWH. Long-term LMWH is burdensome not only because it is expensive, but also because it must be administered subcutaneously.

Comment:

Edoxaban, an oral direct factor Xa inhibitor, has recently been approved in many jurisdictions for the treatment of VTE. Although high-quality evidence indicates that edoxaban (along with other direct oral anticoagulants [DOACs]) is at least as safe and effective as standard therapy for DVT and PE, very few patients participated in the registration trials for these newer anticoagulants had cancer-associated VTE. Furthermore, the principal comparator in the registration trials of edoxaban and other DOACs was warfarin, not LMWH. Therefore, a trial comparing a DOAC to LMWH in patients with cancer-associated thrombosis is much needed.

Given the frequency with which VTE occurs among persons with cancer and the unsatisfactory nature of the best-available therapy, patients would benefit substantially if edoxaban proved to be at least as effective (and as safe) as LMWH in this population.

*Patients randomized to edoxaban will receive five days of therapeutic-dose LMWH, and then switch to edoxaban. Patients with an estimated creatinine clearance lower than 50 mL/min or body weight less than 60 kg will receive 30 mg edoxaban by mouth daily.

Competing Interests

Dr. Garcia has received consulting honoraria from Daiichi Sankyo, the sponsor of the trial described here. Dr. Garcia is the U.S. National Coordinator for this trial.