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JOURNAL ONKOLOGIE – STUDIE
API-CAT

API-CAT STUDY for APIxaban Cancer Associated Thrombosis

Rekrutierend

NCT-Nummer:
NCT03692065

Studienbeginn:
Oktober 2018

Letztes Update:
25.02.2021

Wirkstoff:
Apixaban 5 MG

Indikation (Clinical Trials):
Thrombosis

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Assistance Publique - Hôpitaux de Paris

Collaborator:
Bristol-Myers Squibb

Studienleiter

Guy Meyer, Pr
Study Director
APHP(ASSISTANCE PUBLIQUE DES HOPITAUX DE PARIS

Kontakt

Studienlocations
(3 von 106)

Medical university of Vienna
Vienna
AustriaAktiv, nicht rekrutierend» Google-Maps
HÔPITAL PRIVÉ ARRAS LES BONNETTES - Espace Artois Santé
62012 Arras
FranceAktiv, nicht rekrutierend» Google-Maps
Centre Hospitalier d'Avignon
84000 Avignon
FranceAktiv, nicht rekrutierend» Google-Maps
C.H. Des Pays de Morlaix
29600 Morlaix
FranceAktiv, nicht rekrutierend» Google-Maps
Athens School of Medicine
Athens
GreeceAktiv, nicht rekrutierend» Google-Maps
Amsterdam university medical center
Amsterdam
NetherlandsAktiv, nicht rekrutierend» Google-Maps
Hospital genarl Univ de Albacete
Albacete
SpainAktiv, nicht rekrutierend» Google-Maps
Parc Santari Sant Joan de Deu - Hospital general
Barcelona
SpainAktiv, nicht rekrutierend» Google-Maps
Fundacio Hospital de L'Esperit Sant
Barcelone
SpainAktiv, nicht rekrutierend» Google-Maps
Hospital general Universitario Santa Lucia
Carthagène
SpainAktiv, nicht rekrutierend» Google-Maps
Hospital universitario Infanta Sofia
Madrid
SpainAktiv, nicht rekrutierend» Google-Maps
Istituto Oncologico della svizzera Italiana
Bellinzona
SwitzerlandAktiv, nicht rekrutierend» Google-Maps
Queens centre castle hill hospital
Cottingham
United KingdomAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

For patients completing at least 6 months of anticoagulant therapy in whom the cancer is

active, the thrombotic risk is arguably ongoing and indefinite anticoagulation seems

required.

Given apixaban 5 mg bid is an alternative for the first 6 months of treatment, we intend to

assess whether it is possible to lower the dose of apixaban (2.5 mg bid) after completing at

least 6 months of anticoagulant treatment in a specific population of patients with cancer

associated thrombosis (CAT) requiring extended anticoagulant treatment and with significant

life expectancy. There are 2 conditions to be met : demonstrate the non-inferiority of the

2.5 mg bid regimen on the efficacy endpoint and then demonstrate the superiority of the 2.5

mg bid regimen as compared to the 5 mg bid on the safety endpoint.

It is a multicenter, international, prospective, randomized, parallel-group, double-blind

non-inferiority trial with blinded adjudication of outcome events (approximately 160 centers

in approximately 10 countries (France, Italy, Spain, Belgium, Greece, Netherlands, UK,

Switzerland, Poland, Austria), with a number of expected inclusions of 11 patients per site.

Subjects should be randomized within 7 days after the last dose of their initial 6-month

treatment, defined as the treatment ongoing after completing at least 6 months of

anticoagulant treatment from the beginning of the anticoagulant treatment for the index

event. This treatment may be low-molecular weight heparin (LMWH), direct oral anticoagulant

(DOAC) or vitamin K antagonist (VKA). If a VKA was used as standard anticoagulant therapy,

then an INR must be documented as 2 or less before randomization. Every attempt should be

made to randomize subjects as soon as possible after the initial treatment has been

discontinued.

Subjects will be stratified based on the cancer site and the type of disease treated (PE

with/without DVT or DVT alone). If a subject had both symptomatic DVT and symptomatic PE, the

subject will be stratified as having symptomatic PE.

Ein-/Ausschlusskriterien

Minimum Age: 18 Years

Maximum Age:

Sex: All Gender Based: No Accepts Healthy Volunteers: No

Criteria:

Inclusion Criteria:

- 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 : Symptomatic or incidental proximal lower-limb,

iliac, inferior vena cava DVT or symptomatic or incidental pulmonary embolism in a

segmental or larger pulmonary artery 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).

- Completed at least 6 months of anticoagulant therapy at therapeutic dosage (whatever

the drug and the dosing),or completed assigned a clinical trial study treatment, for

the treatment of the index event and patient still receiving anticoagulant treatment 6

months after occurrence of the VTE index

- No objectively documented symptomatic recurrence of VTE between the index event and

randomization.

- Anticipated duration of anticoagulant treatment of at least 12 months at the time of

randomization

- Patient affiliated to social security for French centers.

Exclusion Criteria:

- 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

1. intracranial or intraocular bleeding within the 6 months

2. major surgery within 2 weeks prior to randomization

3. 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

- 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 acetylsalicylic acid >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 P450 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 (eg, 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).

Studien-Rationale

Primary outcome:

1. The incidence of an an adjudicated composite endpoint (Time Frame - During the treatment period (12 months)):
The incidence of an adjudicated composite of recurrent symptomatic VTE (proximal and/or distal DVT and/or symptomatic PE and/or upper limb or central venous catheter thrombosis or incidental VTE (proximal DVT or PE), or death due to PE during the treatment period. 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 the malignancy or other reasons but not for a VTE suspicion.



Secondary outcome:

1. The incidence of adjudicated major and clinically relevant non-major bleeding (Time Frame - During the treatment period (12 months)):
The definition of major bleeding described is adapted from the International Society on Thrombosis and Hemostasis (ISTH) definition (Schulman JTH 2005).

2. Recurrent symptomatic VTE (Time Frame - During the treatment period (12 months)):
Recurrent VTE objectively confirmed after clinical suspicion

3. VTE related-death (Time Frame - During the treatment period (12 months)):
VTE related-death: PE based on objective diagnostic testing, autopsy, or sudden death; i.e. death occurring within one hour of the onset of new symptoms which cannot be attributed to a documented cause (unexplained death) and for which PE/DVT cannot be ruled out as the cause.

4. All-cause death (Time Frame - During the treatment period (12 months)):
All deaths will be adjudicated by the ICAC and classified as either VTE-related, cancer death (including all deaths due to the underlying cancer), bleeding-related or others, including all deaths due to a clearly documented other cause, such as respiratory failure (e.g., terminal emphysema), infections/sepsis etc.

5. Adjudicated major bleeding. (Time Frame - During the treatment period (12 months)):
The definition of major bleeding described is adapted from the International Society on Thrombosis and Hemostasis (ISTH) definition (Schulman 2005) and includes Acute clinically overt bleeding with one or more of the following: A decrease in hemoglobin (Hgb) of 2 g/dL or more A transfusion of 2 or more units of packed red blood cells Symptomatic bleeding that occurs in at least one of the following critical sites: Intracranial Intraspinal Intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed) Pericardial Intra-articular Intramuscular with compartment syndrome Retroperitoneal Bleeding that is fatal: bleeding event that the independent adjudication committee determines is the primary cause of death or contributes directly to death.

6. Adjudicated composite of recurrent symptomatic VTE, VTE related-death, all-cause death, adjudicated major bleeding. (Time Frame - During the treatment period (12 months)):
Adjudicated composite of recurrent symptomatic VTE, VTE related-death, all-cause death, adjudicated major bleeding.

Studien-Arme

  • Active Comparator: Apixaban film coated tablets 2.5 mg
    Patients randomized in the apixaban reduced dose group will receive an apixaban 2.5 mg tablet and a placebo of apixaban 5 mg tablet, twice daily for 12 months.
  • Active Comparator: Apixaban film coated tablets 5 mg
    Patients randomized in the apixaban full dose group will receive a placebo of apixaban 2.5 mg tablet and an apixaban 5 mg tablet, twice daily for 12 months.

Geprüfte Regime

  • Apixaban 5 MG (Apixaban 2.5 MG):
    Subjects will be randomized (1:1 ratio) to apixaban 5 mg bid (full dose) or apixaban 2.5 mg bid (reduced-dose) using a centralized IWRS (double blind study).

Quelle: ClinicalTrials.gov


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