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

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 940 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.

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 >= 21 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