Direct Oral Anticoagulants (DOACs) Versus LMWH + / - Warfarin for VTE in Cancer

The overarching objective of the study is to determine the effectiveness of LMWH / warfarin vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The intervention strategy is Direct Oral AntiCoagulants (DOAC) therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is low molecular weight heparin (LMWH) alone or with warfarin. The information gained will empower cancer patients and physicians to make more informed choices about anticoagulation strategies to manage VTE.

Inclusion Criteria

• Diagnosis of advanced solid tumor cancer, lymphoma, or myeloma (no time restrictions or limitations) -OR- diagnosis of early stage solid tumor cancer, lymphoma, or myeloma <= 12 months prior to study enrollment
• Diagnosis of VTE <= 30 days prior to study enrollment for which potential benefits of anticoagulation therapy to prevent recurrence of VTE are felt by the treating physician to exceed the potential harms
• Any anticoagulation drug/strategy may be used to treat the index VTE; protocol treatment will begin <= 30days after the index VTE diagnosis date
• Treating physician intends to put participant on anticoagulation therapy for at least three months.
• Age >= 18 years
• Platelet count is >= 50,000/mm^3 (<= 7 days prior to enrollment)
• CrCl (Creatinine Clearance) is >= 15 ml/min (<= 7 days prior to enrollment)

Exclusion Criteria

• Diagnosis of acute leukemia
• Has ever received or is scheduled to receive an Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)
• Patients who have ever received an Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) ARE eligible.
• Patients who are scheduled to receive an Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) are NOT eligible
• Ongoing, clinically significant bleeding (CTCAE grade 3 or 4)
• Ongoing therapy with a P-gp inhibitor (e.g., nelfinavir, indinavir, or saquinavir-protease inhibitors for HIV) as these drugs interact with the factor Xa inhibitors
• Therapy with any azole antifungals (e.g., itraconazole, ketaconazole, voriconazole) at the time of enrollment

Venous blood clots affect nearly a million Americans each year. Venous clots in the legs are

called deep venous thrombosis (DVT) and are dangerous because they travel to the lungs where

they cause blockages known as pulmonary emboli (PE). DVT and PE are called venous

thromboemboli (VTE). Cancer is a risk factor with nearly 200,000 VTEs in cancer patients each

year. The purpose of VTE treatment is to prevent the initial clot from spreading and to

prevent new clots from forming. This is accomplished by thinning the blood, or

anticoagulation. Without anticoagulation, VTEs recur and are often fatal.

Recently, the FDA has approved 4 new Direct Oral AntiCoagulants (DOACs) for preventing VTE

recurrence. Few cancer patients were included in the efficacy trials, and practice guidelines

fall silent on whether switching to DOAC therapy is advisable. To fill this knowledge gap,

the Alliance Foundation Trials LLC, a research network of academic and community practices

across the US, is conducting a pragmatic randomized effectiveness trial.

The overarching objective of the study is to determine the effectiveness of LMWH/ warfarin

vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The investigators

will conduct a trial of 811 cancer patients followed for 6 months. The intervention strategy

is DOAC therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is LMWH

alone or with warfarin. Within each arm, patients can choose the agent they prefer based on

side effects, drug interactions, and practical issues such as co-pays. The trial compares

these two strategies in terms of treatment: 1) benefits based on VTE recurrence; 2) harms

based on bleeding rates; 3) burdens based on patients' reports of their experiences; and 4)

mortality rates.

The investigators hypothesize that the benefits, harms and burdens of DOAC treatment will be

non-inferior to, or better than, usual care with LMWH/ warfarin among cancer patients. The

information gained will empower cancer patients and physicians to make more informed choices

about anticoagulation strategies to manage VTE.

Trial Phase Phase NA

Trial Type Treatment

Lead Organization
Alliance Foundation Trials, LLC.

• Primary ID AFT-28
• Secondary IDs NCI-2017-00200, CER-1503-29805
• Clinicaltrials.gov ID NCT02744092