Cancer Associated Thrombosis, a Pilot Treatment Study Using Rivaroxaban

NCT ID: NCT02746185

Last Updated: 2018-08-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 159 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-30
• Study Completion Date: 2018-04-25

Brief Summary

The study will compare the efficacy and safety of oral rivaroxaban and subcutaneous dalteparin in patients with cancer associated thrombosis. It is designed as a non-inferiority open label randomized multicenter trial with blinded adjudication of outcome events.

Detailed Description

Patients with active cancer and symptomatic pulmonary embolism, proximal deep vein thrombosis, iliac or caval thrombosis will be randomly assigned to receive either dalteparin using the CLOT regimen or to oral rivaroxaban using the conventional dosage given in the Einstein studies. Experimental and control treatments will be given for three months. The main outcome at three month will include all symptomatic and incidentally discovered venous thromboembolic events including pulmonary embolism (either objectively confirmed and death due to pulmonary embolism), lower limb and upper limb deep vein thrombosis, iliac, caval and visceral thrombosis and any worsening of vascular obstruction which will be collected systematically at inclusion and at day 90. The safety end-points will consist of the rate of major bleedings and the composite of major and non-major but clinically significant bleedings at day 90. All outcome events will be blindly adjudicated by a central independent adjudication committee.

Conditions

Neoplasm; Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Low-molecular-weight heparin

dalteparin, 200 IU/kg subcutaneously once daily for one month followed by 150 IU/kg subcutaneously once daily for 2 months

Group Type: ACTIVE_COMPARATOR

Low-molecular-weight heparin

Intervention Type: DRUG

dalteparin, 200 IU/kg OD for 4 weeks followed by 150 IU/kg OD for 8 weeks

Rivaroxaban

rivaroxaban, orally, 15 mg twice daily for 3 weeks followed by 20 mg once daily for 9 weeks

Group Type: EXPERIMENTAL

rivaroxaban

Intervention Type: DRUG

rivaroxaban, 15 mg BD (Bis in die) for 3 weeks followed by 20mg OD (Omni die) for 9 weeks

Interventions

rivaroxaban

rivaroxaban, 15 mg BD (Bis in die) for 3 weeks followed by 20mg OD (Omni die) for 9 weeks

Intervention Type: DRUG

Low-molecular-weight heparin

dalteparin, 200 IU/kg OD for 4 weeks followed by 150 IU/kg OD for 8 weeks

Intervention Type: DRUG

Other Intervention Names

xarelto; dalteparin

Eligibility Criteria

Inclusion Criteria

• Age > 18 years
• Social security affiliation
• Written informed consent
• Solid active cancer, high grade lymphoma or myeloma treated with Immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide). Active cancer is defined as the presence of measurable disease or ongoing (or planned) chemotherapy, radiotherapy or targeted therapy at inclusion.
• Histologically or cytologically proven cancer.
• Symptomatic venous thromboembolism objectively confirmed diagnosed because of symptoms or discovered incidentally
• High-risk of recurrent Venous thromboembolism (VTE) defined by a score of 0 or ≥ 1, using the following criteria: female sex (+1), lung cancer (+1), breast cancer (-1) non metastatic tumor (-2), previous VTE (+1).

Exclusion Criteria

• Exclusive adjuvant hormonal treatment with no measurable residual disease
• Sub-segmental isolated pulmonary embolism (PE) without associated proximal DVT
• Isolated distal deep vein thrombosis (DVT) of the legs
• Isolated upper-extremity DVT or superior vena cava thrombosis
• Isolated visceral thrombosis
• Platelet count < 50 000 G/L
• Active bleeding
• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C
• Hemostatic defect with contraindication to anticoagulant treatment at therapeutic dosage
• Vena cava filter at inclusion
• Fibrinolytic therapy within 3 days preceding inclusion
• Creatinine clearance < 30 ml/min according to Cockcroft-Gault formula
• Previous heparin-induced thrombocytopenia
• Anticoagulant treatment at curative dosage for more than 3 days before inclusion
• Pregnancy or lack of effective contraceptive treatment for women of childbearing age
• Treatment with both strong CYP3A4 and P-glycoprotein (PgP) inhibitors: protease inhibitors for HIV disease, systemic ketoconazole
• Treatment with a strong CYP3A4 inducer: rifampicin, carbamazepine, phenytoin.
• Life expectancy < 3 months
• Eastern Cooperative Oncology Group (ECOG) level 3 or 4

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guy Meyer, MD

Role: PRINCIPAL_INVESTIGATOR

APHP - HEGP

Locations

CHU Amiens - Medecine vasculaire (003)

Amiens, , France

CHU Angers - Medecin Interne (002)

Angers, , France

Espace Artois Santé

Arras, , France

Hopital Saint Andre - Medecine vasculaire (015)

Bordeaux, , France

CHU Brest - Departement de medecin interne et pneumologie (008)

Brest, , France

CHU Le Bocage - Medecine interne 1 (014)

Dijon, , France

CHU Grenoble - Medecine vasculaire (007)

Grenoble, , France

CH Départemental La Roche sur Yon

La Roche-sur-Yon, , France

Centre hospitalier Lyon Sud - Medecine interne (011)

Lyon, , France

CHRU de Nîmes - Pneumologie (012)

Nîmes, , France

HEGP - Pneumologie et soins intensifs (001)

Paris, , France

Institut Curie - Soins de support en Cancerologie (020)

Paris, , France

CHU Saint Etienne - Medecin vasculaire et therapeutique (006)

Saint-Etienne, , France

Hopital Saine Musse - Service de Medecine Vasculaire (010)

Toulon, , France

CHU Rangueil - Medecin Vasculaire (019)

Toulouse, , France

Countries

France

References

Planquette B, Bertoletti L, Charles-Nelson A, Laporte S, Grange C, Mahe I, Pernod G, Elias A, Couturaud F, Falvo N, Sevestre MA, Ray V, Burnod A, Brebion N, Roy PM, Timar-David M, Aquilanti S, Constans J, Bura-Riviere A, Brisot D, Chatellier G, Sanchez O, Meyer G, Girard P, Mismetti P; CASTA DIVA Trial Investigators. Rivaroxaban vs Dalteparin in Cancer-Associated Thromboembolism: A Randomized Trial. Chest. 2022 Mar;161(3):781-790. doi: 10.1016/j.chest.2021.09.037. Epub 2021 Oct 8.

Reference Type: DERIVED

PMID: 34627853 (View on PubMed)

Riaz IB, Fuentes HE, Naqvi SAA, He H, Sipra QR, Tafur AJ, Padranos L, Wysokinski WE, Marshall AL, Vandvik PO, Montori V, Bryce AH, Liu H, Badgett RG, Murad MH, McBane RD 2nd. Direct Oral Anticoagulants Compared With Dalteparin for Treatment of Cancer-Associated Thrombosis: A Living, Interactive Systematic Review and Network Meta-analysis. Mayo Clin Proc. 2022 Feb;97(2):308-324. doi: 10.1016/j.mayocp.2020.10.041. Epub 2021 Jun 22.

Reference Type: DERIVED

PMID: 34172290 (View on PubMed)

Other Identifiers

P141204

Identifier Type: -

Identifier Source: org_study_id