Clinical trial NCT05171075: A Study Comparing Abelacimab to Dalteparin in the Treatment of Gastrointestinal/Genitourinary Cancer and Associated VTE
Official title: A Multicenter, Randomized, Open-label, Blinded Endpoint Evaluation, Phase 3 Study Comparing the Effect of Abelacimab vs. Dalteparin on Venous Thromboembolism (VTE) Recurrence and Bleeding in Patients With GI/GU Associated VTE
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Venous Thromboembolism
Deep Venous Thrombosis
Pulmonary Embolism
Keywords: Anticoagulants
VTE recurrence rate
PROBE design
LMWH
CAT
Cancer associated VTE
GI cancer
Abelacimab
Dalteparin
GU cancer
FXI
Major bleeding events
CRNM bleeding events
Lead sponsor: Anthos Therapeutics, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Itreas
First posted: 2021-12-28
Enrollment: 1020
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 3, multicenter, open-label, blinded endpoint study to evaluate the effect of abelacimab relative to dalteparin on venous thromboembolism (VTE) recurrence and bleeding in patients with gastrointestinal (GI)/genitourinary (GU) cancer associated VTE (Magnolia)

Detailed description: Cancer associated thrombosis (CAT) is a severe medical condition which is characterized by high incidence of Venous thromboembolism (VTE) recurrence and high risk for bleeding. Patients with intact GI and GU cancer have increased bleeding risk with oral direct anticoagulants (DOACs), Guidelines advice caution with those DOACs or state preference for low molecular weight heparin (LMWH) in this population. The ANT-008 study will compare treatment with abelacimab monthly administration to LMWH daily subcutaneous (sc) administration over 6-month treatment. The study outcomes include VTE recurrence, bleeding event and treatment discontinuation at 6 months

Eligibility criteria: Inclusion Criteria:

* Male or female subjects ≥18 years old or other legal maturity age according to the country of residence
* Confirmed GI (colorectal, pancreatic, gastric, esophageal, gastro-esophageal junction or hepatobiliary) or confirmed GU (renal, ureteral, bladder, prostate, or urethra) cancers if:

  * Unresectable, locally advanced, metastatic, or non-metastatic GI/GU cancer and
  * No intended curative surgery during the study
* Confirmed symptomatic or incidental proximal lower limb deep vein thrombosis (DVT) (i.e., popliteal, femoral, iliac, and/or inferior vena cava vein thrombosis) and/or a confirmed symptomatic pulmonary embolism (PE), or an incidental PE in a segmental, or larger pulmonary artery. Patients are eligible within 120 hours from diagnosis of the qualifying VTE.
* Anticoagulation therapy with LMWH for at least 6 months is indicated
* Able to provide written informed consent

Exclusion Criteria:

* Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) occurrence of DVT and/or PE
* More than 120 hours of pre-treatment with therapeutic doses of UFH, LMWH, or other anticoagulants
* An indication to continue treatment with therapeutic doses of an anticoagulant other than for VTE treatment prior to randomization (e.g., atrial fibrillation, mechanical heart valve, prior VTE)
* PE leading to hemodynamic instability (systolic BP \<90 mmHg or shock).
* Acute ischemic or hemorrhagic stroke or intracranial hemorrhage, in the last 4 weeks preceding screening.
* Brain trauma, or cerebral or a spinal cord surgery or spinal procedures such as lumbar puncture or epidural/spinal anesthesia within 4 weeks of screening
* Need for aspirin in a dosage of more than 100 mg/day or, any other antiplatelet agent alone or in combination with aspirin
* Bleeding requiring medical attention at the time of randomization or in the preceding 4 weeks
* Planned brain, spinal cord, cardiac, vascular, major thoracic and/or major abdominal surgery in the 4 weeks following randomization
* History of heparin induced thrombocytopenia
* Infective acute or subacute endocarditis at the time of presentation
* Primary brain cancer or untreated intracranial metastasis
* Eastern Cooperative Oncology Group (ECOG) performance status of 3 or 4 at screening
* Life expectancy of \<3 months at randomization
* Calculated creatinine clearance (CrCl) \<30 mL/min at the screening visit
* Platelet count \<50,000/ mm3 at the screening visit
* Hemoglobin \<8 g/dL at the screening visit
* Acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase ≥3 times and/or bilirubin ≥2 times the upper limit of normal (ULN) at the screening visit in the absence of clinical explanation
* Uncontrolled hypertension (systolic blood pressure \[BP\] \> 180 mm Hg or diastolic BP \>100 mm Hg despite antihypertensive treatment)
* Women of child-bearing potential (WOCBP) who are unwilling or unable to use highly effective contraceptive measures during the study from screening up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
* Sexually active males with sexual partners of childbearing potential must agree to use a condom or other reliable contraceptive measure up to 3 days after last treatment of dalteparin or 100 days after administration of abelacimab
* Pregnant or breast-feeding women
* History of hypersensitivity to any of the study drugs (including dalteparin) or its excipients, to drugs of similar chemical classes, or any contraindication listed in the label for dalteparin
* Subjects with any condition that in the judgement of the Investigator would place the subject at increased risk of harm if he/she participated in the study
* Use of other investigational (not-registered) drugs within 5 half-lives prior to enrollment or until the expected pharmacodynamic effect has returned to baseline, whichever is longer. Participation in academic non-interventional studies or interventional studies, comprising testing different strategies or different combinations of registered drugs is permitted.

Primary outcomes:
measure: Time to first event of centrally adjudicated VTE recurrence consisting of new proximal deep venous thrombosis, new pulmonary embolism (PE) or fatal PE, including unexplained death for which PE cannot be ruled out
timeFrame: 6 months
Secondary outcomes:
measure: Time to first event of ISTH-adjudicated major or clinically relevant non-major (CRNM) bleeding events
timeFrame: 6 months
measure: Net clinical benefit defined as survival without VTE recurrence, or major or CRNM bleeding
timeFrame: 6 months
Other outcomes:
Locations:
city: Aurora
country: United States
facility: University of Colorado Anschutz Medical Campus
state: Colorado
city: Washington
country: United States
facility: Washington DC VAMC
state: District of Columbia
city: Miami
country: United States
facility: University of Miami Health System/Sylvester Comprehensive Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute of Emory University
state: Georgia
city: Evanston
country: United States
facility: NorthShore University Health System
state: Illinois
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Barnes-Jewish Hospital
state: Missouri
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center-Middletown
state: New Jersey
city: Commack
country: United States
facility: Memorial Sloan Kettering Cancer Center-Commack
state: New York
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center-West Harrison
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania - Penn Blood Disorders Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Hospital
state: Pennsylvania
city: San Antonio
country: United States
facility: University of Texas Mays Cancer Center
state: Texas
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Epping
country: Australia
facility: Northern Health
state: Victoria
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Perth
country: Australia
facility: Perth Blood Institute
city: Prahran
country: Australia
facility: The Alfred Hospital
city: Graz
country: Austria
facility: LKH - Universitätsklinikum Graz
city: Neustadt
country: Austria
facility: LK Wiener Neustadt
city: Vienna
country: Austria
facility: Medical University of Vienna
city: Hamilton
country: Canada
facility: Hamilton Health Sciences, Juravinski Hospital and Cancer Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Instituite
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Instituite
state: Ontario
city: Saint Catharines
country: Canada
facility: Niagara Health System
state: Ontario
city: Montréal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Montréal
country: Canada
facility: McGill University Health Centre
state: Quebec
city: Calgary
country: Canada
facility: University of Calgary
city: Marie
country: Canada
facility: Sault Area Hospital
city: Toronto
country: Canada
facility: Toronto General Hospital
city: Beijing
country: China
facility: Beijing Shijitan Hosp.
city: Beijing
country: China
facility: Peking University Third Hospital
city: Ch'ang-ch'un
country: China
facility: Jilin Province Tumor Hospital
city: Guangdong
country: China
facility: Southern Medical University - Zhujiang Hospital
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
city: Guangzhou
country: China
facility: The Sixth Affiliated Hospital of Sun Yat-Sen University
city: Huizhou
country: China
facility: Huizhou Municipal Central Hospital
city: Nanjing
country: China
facility: Nanjing First Hospital
city: Tongzhou
country: China
facility: Nantong Tumor Hospital (Tumor Hospital Affiliated to Nantong University )
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science &Technology
city: Wuhan
country: China
facility: Hubei Cancer Hospital
city: Zhejiang
country: China
facility: The Second Hospital of Jiaxing
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Hradec Králové
country: Czechia
facility: University Hospital Hradec Kralove
city: Nová Ves Pod Pleší
country: Czechia
facility: Nemocnice Na Pleši s.r.o.
city: Prague
country: Czechia
facility: Onkologická klinika VFN a 1. LF UK
city: Praha
country: Czechia
facility: Thomayerova nemocnice
city: Brest
country: France
facility: CHU de Brest - Hôpital de la Cavale Blanche
state: Cedex
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
state: Cedex
city: Le Puy-en-Velay
country: France
facility: CH Le Puy en Velay
state: Chantemesse
city: Colombes
country: France
facility: Hôpital Louis Mourier
state: Renouiflers
city: Vandœuvre-lès-Nancy
country: France
facility: CHU de Nancy - Hôpital de Brabois Adultes
state: Rue Du Morvan
city: Amiens
country: France
facility: CHU Amiens - Hopital Nord
city: Angers
country: France
facility: CHU Angers - Hôpital Hôtel Dieu
city: Clermont-Ferrand
country: France
facility: CHU Clermont Ferrand - Hopital Gabriel Montpied
city: Dijon
country: France
facility: CHU Dijon - Hôpital Bocage Central
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Albert Michallon
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Marseille
country: France
facility: Hopital Timone Adultes
city: Paris
country: France
facility: Groupe Hospitalier Pitie-Salpetriere
city: Paris
country: France
facility: Hôpital Européen Georges Pompidou
city: Pierre-Bénite
country: France
facility: Hospices Civils de Lyon (HCL) - Centre Hospitalier Lyon-Sud
city: Rouen
country: France
facility: CHU de Rouen - Hôpital de Bois Guillaume
city: Saint-Étienne
country: France
facility: CHU de Saint-Etienne - Hopital Nord
city: Strasbourg
country: France
facility: CHU Strasbourg - Nouvel Hôpital Civil
city: Strasbourg
country: France
facility: Nouvel Hôpital Civil de Strasbourg
city: Toulon
country: France
facility: Centre Hospitalier Intercommunal de Toulon
city: Vandœuvre-lès-Nancy
country: France
facility: CHU de Nancy - Hôpital de Brabois Adultes
city: Dresden
country: Germany
facility: Staedtisches Klinikum Dresden Standort Dresden-Friedrichstadt
city: Dresden
country: Germany
facility: Universitaetsklinikum Carl Gustav Carus TU Dresden
city: Görlitz
country: Germany
facility: Praxis für Gefäßmedizin
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf
city: Kiel
country: Germany
facility: Universitätsklinik der Christian-Albrechts-Universität
city: Leipzig
country: Germany
facility: Universitätsklinik Leipzig
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet
city: Debrecen
country: Hungary
facility: Debreceni Egyetem
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz es Rendelointezet
city: Kecskemét
country: Hungary
facility: Bacs-Kiskun County Hospital
city: Pécs
country: Hungary
facility: University of Pécs
city: Cork
country: Ireland
facility: Cork University Hospital
city: Cork
country: Ireland
facility: Bon Secour Hospital
city: Dublin
country: Ireland
facility: Beaumont Hospital
city: Limerick
country: Ireland
facility: University Hospital, Limerick
city: Bari
country: Italy
facility: IRCCS Istituto Tumori Giovanni Paolo II
city: Bergamo
country: Italy
facility: Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
city: Bologna
country: Italy
facility: Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
city: Castelfranco Veneto
country: Italy
facility: Presidio Ospedaliero di Castelfranco Veneto
city: Chieti
country: Italy
facility: SS. ma Annunziata
city: Cosenza
country: Italy
facility: Ospedale Civile Dell Annunziata
city: Faenza
country: Italy
facility: Ospedale Degli Infermi
city: Genova
country: Italy
facility: Azienda Ospedaliero Universitaria San Martino
city: Grosseto
country: Italy
facility: Presidio Ospedaliero della Misericordia
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Santi Paolo e Carlo
city: Modena
country: Italy
facility: A.O.U. Policlinico di Modena
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione G. Pascale
city: Padova
country: Italy
facility: Azienda Ospedale - Università Padova
city: Padova
country: Italy
facility: Ospedale Universitario
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
city: Perugia
country: Italy
facility: Universit degli Studi di Perugia - Azienda Ospedaliera di Perugia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Reggio Emilia
country: Italy
facility: Arcispedale S. Maria Nuova Azienda Ospedaliera di Reggio Emilia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli IRCCS.
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Treviso
country: Italy
facility: Ospedale Santa Maria di Cà Foncello
city: Udine
country: Italy
facility: Azienda Ospedaliero-Universitaria Santa Maria della Misericordia
city: Varese
country: Italy
facility: Università dell'Insubria
city: Venezia
country: Italy
facility: Ospedale SS. Giovanni e Paolo
city: Verduno
country: Italy
facility: Ospedalemichele e Pietro ferrer
city: Vicenza
country: Italy
facility: Ospedale San Bortolo di Vicenza
city: Anyang-Si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
city: Bucheon
country: Korea, Republic of
facility: SoonChunHyang University Hospital Bucheon
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Daegu
country: Korea, Republic of
facility: Daegu Catholic University Medical Center
city: Gyeonggi-do
country: Korea, Republic of
facility: Yongin Severance Hospital, Yonsei University Health System
city: Jeonju
country: Korea, Republic of
facility: Myongji Hospital
city: Jeonju
country: Korea, Republic of
facility: Jeonbuk National University Hospital
city: Pusan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Soonchunhyang University Seoul Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University Hospital at Gangdong
city: Seoul
country: Korea, Republic of
facility: Ewha Womans University Mokdong Hospital
city: Daugavpils
country: Latvia
facility: Daugavpils Regional Hospital
city: Liepāja
country: Latvia
facility: Liepaja Regional Hospital
city: Riga
country: Latvia
facility: Pauls Stradins CUH
city: Riga
country: Latvia
facility: Riga East Clinical University Hospital
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis, Locatie Oost
city: Beverwijk
country: Netherlands
facility: Rode Kruis Ziekenhuis
city: Den Haag
country: Netherlands
facility: Haga Ziekenhuis
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Dordwijk
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Haarlem
country: Netherlands
facility: Spaarne Gasthuis (Kennemer Gasthuis) - Haarlem-Zuid
city: Hilversum
country: Netherlands
facility: Tergooiziekenhuizen, Hilversum
city: Holland
country: Netherlands
facility: Amsterdam University Medical Center
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Ikazia Ziekenhuis
city: Fredrikstad
country: Norway
facility: Østfold Hospital Kalnes
city: Lørenskog
country: Norway
facility: Akershus Univeristy Hospital
city: Oslo
country: Norway
facility: Oslo University Hospital, Dep of Haematology
city: Alicante
country: Spain
facility: Hospital Universitario Del Vinalopo
city: Barcelona
country: Spain
facility: Complejo Hospital Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu I Sant Pau
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves
city: Jaén
country: Spain
facility: Hospital Universitario Ciudad de Jaen
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Hospital Universitario Infanta Leonor
city: Madrid
country: Spain
facility: MD Anderson Cancer Centre
city: Majadahonda
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
city: Ourense
country: Spain
facility: Complejo Hospitalario Universitario de Ourense
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturia
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
city: Santander
country: Spain
facility: Hospital Universitario Marques de Valdecilla
city: Santiago De Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Sundsvall
country: Sweden
facility: Länssjukhuset Sundsvall-Härnösand
city: Geneve
country: Switzerland
facility: Hopital Universitaire Geneve
city: Zürich
country: Switzerland
facility: University of Zürich
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung-Ho Memorial Hospital
city: New Taipei City
country: Taiwan
facility: Far Eastern Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University (NCKU) Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
state: England
city: London
country: United Kingdom
facility: Barts Health NHS Trust
state: England
city: Cottingham
country: United Kingdom
facility: Castle Hill Hospital, Department of Oncology & Haematology
state: ENG
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals
state: ENG
city: Glasgow
country: United Kingdom
facility: Queen Elizabeth University Hospital Campus
state: SCO
Study officials:
References: