Long-term treatment of cancer associated venous thromboembolism: reduced vs full dose of apixaban : API-CAT STUDY for APIxaban Cancer Associated Thrombosis

• Signed Written Informed Consent
• Any cancer diagnosed histologically (other than basal-cell or squamous-cell
carcinoma of the skin, primary brain tumor or intra-cerebral metastasis)
• Active cancer defined as the presence of measurable disease or ongoing (or
planned) chemotherapy, radiotherapy, hormonotherapy, targeted therapy,
immunotherapy at inclusion.
• Objectively documented index event of :
symptomatic or incidental proximal lower-limb, iliac, inferior vena cava
DVT or symptomatic or incidental PE in a segmental or larger pulmonary artery
(1) Proximal DVT is defined as DVT that involves at least the popliteal vein or
a more proximal vein, demonstrated by imaging with compression ultrasound
(CUS), including grey-scale or color-coded Doppler, or ascending contrast
venography or contrast enhanced computed tomography or magnetic resonance
imaging.
(2) PE has to be demonstrated by imaging as follows:
* an intraluminal filling defect in segmental or more proximal branches on
contrast enhanced chest computed tomography or on computed tomography pulmonary
angiography ; or
* an intraluminal filling defect or a sudden cutoff of vessels more than 2.5 mm
in diameter on the pulmonary angiogram; or
* a perfusion defect of at least 75% of a segment with a local normal
ventilation result (high-probability) on ventilation/perfusion lung scan (VPLS)
(3) Incidental VTE is defined as proximal DVT or PE detected by imaging
incidentally when a patient undergoes imaging studies as standard of care for
the management of his or her malignancy or other reasons but not for a VTE
suspicion(e.g. cancer diagnosis or staging).• At least 6 months of
anticoagulant therapy at therapeutic dosage (whatever the drug and the dosing),
or completed assigned clinical trial study treatment, for the treatment of the
index event; and patient still receiving anticoagulant treatment after
occurrence or the index VTE .
• No objectively documented symptomatic recurrence of VTE between the index
event and randomization.

• WOCBP who are unwilling or unable to use an acceptable method of birth
control [such as oral contraceptives, other hormonal contraceptives (vaginal
products, skin patches, or implanted or injectable products), or mechanical
products such as an intrauterine device or barrier methods (condoms)] to avoid
pregnancy for the entire study • Women who are pregnant or breastfeeding •
Women with a positive pregnancy test on enrollment or prior to investigational
product administration • Isolated sub-segmental (incidental or symptomatic) PE
without associated DVT • Isolated distal DVT of the legs • Isolated
upper-extremity DVT or superior vena cava thrombosis • Isolated visceral
thrombosis • Isolated catheter thrombosis • Objectively documented symptomatic
recurrence of VTE after the index event under anticoagulant treatment • VTE
during anticoagulant treatment given at therapeutic dosage • Subjects with
indications for long-term treatment with a VKA, such as: - Mechanical heart
valve - Antiphospholipid syndrome • Subjects with indication for long-term
anticoagulation with a VKA or a DOAC at therapeutic dosage • Conditions
increasing the risk of serious bleeding - intracranial or intraocular bleeding
within the 6 months - major surgery within 2 weeks prior to randomization -
overt major bleeding at time of randomization • Life expectancy < 12 months
• Eastern Cooperative Oncology Group (ECOG) level 3 or 4 • Bacterial
endocarditis • Uncontrolled hypertension: systolic blood pressure >180 mm Hg
or diastolic blood pressure >110 mm Hg • Platelet count < 75,000/mm3 •
Hemoglobin < 8g /dl • Creatinine clearance < 30 ml /min based on the
Cockcroft Gault equation (see Section 5.7.4) • Acute hepatitis, chronic active
hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or
more and/or bilirubin level 2 times or more higher the upper limit of the
normal range • Subjects requiring ASA >165 mg/day at randomization or
thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) • Subjects
requiring dual anti-platelet therapy (such as acetylsalicylic acid plus
clopidogrel or acetylsalicylic acid plus ticlopidine) at randomization.
Subjects who transition from dual antiplatelet therapy to monotherapy prior to
randomization will be eligible for the trial • Concomitant use of strong
inhibitors of both cytochrome P-450 3A4 and P Glycoprotein (e.g. human
immunodeficiency virus protease inhibitors or systemic ketoconazole) or strong
inducers of both cytochrome P-450 3A4 and P Glycoprotein (e.g. rifampicin,
carbamazepine, or phenytoin) • Prisoners or subjects who are involuntarily
incarcerated • Subjects who are compulsorily detained for treatment of either a
psychiatric or physical (e.g. infectious disease) illness • Hypersensitivity to
apixaban • Subjects participating in another pharmaco therapeutic program with
an experimental therapy that is known to affect the coagulation system • Under
18 years old • Patients under legal protection (guardianship; court decision)