Cancer Associated Thrombosis, a Pilot Treatment Study Using Rivaroxaban

NCT02746185 | Completed Phase 3 DMC

• 1 other identifier: P141204
• Study Type: interventional
• Target: 159
• Locations: 1 country
• Sites: 15

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.

Conditions

Neoplasm; Venous Thromboembolism

Keywords

cancer; venous thromboembolism; low-molecular weight heparin; rivaroxaban

Outcome Measures

Primary Outcomes (4)

• Symptomatic DVT

  Recurrent VTE during the 3-month treatment period including all symptomatic DVT (lower limbs distal and proximal DVTs, iliac and caval thrombosis, visceral thrombosis and deep vein thrombosis of the arm)

  3 months

• Symptomatic PE

  Recurrent VTE during the 3-month treatment period including symptomatic PE

  3 months

• Unsuspected PE and DVT

  Recurrent VTE during the 3-month treatment period including clinically unsuspected PE and DVT discovered incidentally

  3 months

• Worsening of pulmonary vascular or venous obstruction

  Recurrent VTE during the 3-month treatment period including worsening of pulmonary vascular obstruction or venous obstruction on the systematic examinations performed at the end of the 3-month treatment period

  3 months

Secondary Outcomes (4)

• Major and clinically significant bleedings during the 3-month treatment period

  3 months

• Symptomatic recurrences of PE or DVT of the legs

  3 months

• Major and non-major clinically significant bleedings at day 90

  3 months

• Mortality

  3 months

Other Outcomes (1)

• Rivaroxaban plasma concentrations

  3 months

Study Arms (2)

Low-molecular-weight heparin

ACTIVE COMPARATOR

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

Drug: Low-molecular-weight heparin

Rivaroxaban

EXPERIMENTAL

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

Drug: rivaroxaban

Interventions

rivaroxaban DRUG

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

Also known as: xarelto

Rivaroxaban

Low-molecular-weight heparin DRUG

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

Also known as: dalteparin

Low-molecular-weight heparin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years
• Social security affiliation
• Written informed consent
• 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).

You may not qualify if:

• 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
• Creatinine clearance \< 30 ml/min according to Cockcroft-Gault formula
• Previous heparin-induced thrombocytopenia
• 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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Bayer: collaborator

Study Sites (15)

CHU Amiens - Medecine vasculaire (003)

Amiens, France

Location

CHU Angers - Medecin Interne (002)

Angers, France

Location

Espace Artois Santé

Arras, France

Location

Hopital Saint Andre - Medecine vasculaire (015)

Bordeaux, France

Location

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

Brest, France

Location

CHU Le Bocage - Medecine interne 1 (014)

Dijon, France

Location

CHU Grenoble - Medecine vasculaire (007)

Grenoble, France

Location

CH Départemental La Roche sur Yon

La Roche-sur-Yon, France

Location

Centre hospitalier Lyon Sud - Medecine interne (011)

Lyon, France

Location

CHRU de Nîmes - Pneumologie (012)

Nîmes, France

Location

HEGP - Pneumologie et soins intensifs (001)

Paris, 75015, France

Location

Institut Curie - Soins de support en Cancerologie (020)

Paris, France

Location

CHU Saint Etienne - Medecin vasculaire et therapeutique (006)

Saint-Etienne, France

Location

Hopital Saine Musse - Service de Medecine Vasculaire (010)

Toulon, France

Location

CHU Rangueil - Medecin Vasculaire (019)

Toulouse, France

Location

Related Publications (2)

• 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.

  PMID: 34627853 DERIVED

• 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.

  PMID: 34172290 DERIVED

MeSH Terms

Conditions

Neoplasms; Venous Thromboembolism

Interventions

Rivaroxaban; Heparin, Low-Molecular-Weight; Dalteparin

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Guy Meyer, MD

  APHP - HEGP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: April 21, 2016
• Study Start: September 1, 2016
• Primary Completion: April 25, 2018
• Study Completion: April 25, 2018
• Last Updated: August 13, 2018

Record last verified: 2018-08

Locations

FR (15)