Cancer Venous Thromboembolism (VTE)

NCT02073682 | Completed Phase 3 Results DMC

• 2 other identifiers: DU176b-D-U3112014-004708-30
• Study Type: interventional
• Target: 1,046
• Locations: 6 countries
• Sites: 9

Brief Summary

The primary objective is to demonstrate the non-inferiority of edoxaban (preceded by a short course of LMWH) compared with dalteparin for the prevention of the combined outcome of recurrent venous thromboembolism (VTE) or major bleeding in subjects with VTE associated with cancer during a 12-month study period. If non-inferiority is established, LMWH/edoxaban will be compared with dalteparin for superiority.

Conditions

Venous Thromboembolism (VTE); Deep Vein Thrombosis (DVT); Pulmonary Embolism (PE); Cancer

Keywords

Active Cancer with Metastasis

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event

  12 months

Secondary Outcomes (6)

• Number of Participants With Adjudicated Major Bleeding Events While on Treatment

  12 months

• Number of Participants With Recurrent Venous Thromboembolism (VTE) During the Overall Study Period

  12 months

• Number of Participants With Recurrent Deep Vein Thrombosis (DVT) During the Overall Study Period

  12 months

• Number of Participants With Recurrent Non-Fatal Pulmonary Embolism (PE) During the Overall Study Period

  12 months

• Number of Participants With VTE-Related Death

  12 months

Study Arms (2)

Edoxaban group

EXPERIMENTAL

After 5 days of low molecular weight heparin (LMWH), patients receive edoxaban treatment daily - tablet for oral use

Drug: Edoxaban; Drug: Low molecular weight heparin

Dalteparin group

ACTIVE COMPARATOR

Participants receive Dalteparin treatment daily -solution for subcutaneous injection

Drug: Dalteparin

Interventions

Edoxaban DRUG

After the 5 day treatment with LMWH, patients receive edoxaban 60 mg once daily (QD) as 2 × 30 mg tablets (or 1 x 30 mg tablet QD for patients requiring dose adjustment) for the remainder of the treatment period.

Also known as: DU-176b

Edoxaban group

Dalteparin DRUG

Dalteparin was administered via subcutaneous injection at a dose of 200 IU/kg (maximum daily dose 18,000 IU) for 30 days, and at a dose of 150 IU/kg from Day 31 to the end of treatment.

Also known as: Active comparator

Dalteparin group

Low molecular weight heparin DRUG

Therapeutic doses of subcutaneous LMWH were administered for at least 5 days (to patients in the edoxaban group); this 5-day period may have included the pre-randomization LMWH (if applicable). The choice of parenteral LMWH was up to the treating physician.

Also known as: LMWH

Edoxaban group

Eligibility Criteria

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

You may qualify if:

• Male or female subjects with age ≥ 18 years or the otherwise legal lower age according to the country of residence;
• Confirmed acute lower extremity proximal DVT or PE for which long term treatment with low molecular weight heparin (LMWH) is indicated;
• Cancer, other than basal-cell or squamous-cell carcinoma of the skin;
• Able to provide written informed consent.

You may not qualify if:

• Thrombectomy, insertion of a caval filter, or use of a fibrinolytic agent to treat the current (index) episode of DVT and/or PE;
• Treatment with therapeutic doses of an anticoagulant other than that used for pretreatment of the current (index) VTE episode prior to randomization;
• Active bleeding or high risk for bleeding contraindicating treatment with LMWH or edoxaban;
• Any other contraindication listed in the local labeling of dalteparin, enoxaparin, or edoxaban;

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (9)

Unknown Facility

Brandon, Florida, United States

Location

Unknown Facility

Jonesboro, Georgia, United States

Location

Unknown Facility

Detroit, Michigan, United States

Location

Unknown Facility

Norfolk, Virginia, United States

Location

Unknown Facility

Leuven, Vlaams-Brabant, Belgium

Location

Unknown Facility

Saint-Etienne, France

Location

Unknown Facility

Debrecen, Hajdu-Bihar Megye, Hungary

Location

Unknown Facility

Varese, Italy

Location

Unknown Facility

Amsterdam, Netherlands

Location

Related Publications (3)

• Patell R, Hsu C, Shi M, Grosso MA, Duggal A, Buller HR, Raskob G, Zwicker JI. Impact of mild thrombocytopenia on bleeding and recurrent thrombosis in cancer. Haematologica. 2024 Jun 1;109(6):1849-1856. doi: 10.3324/haematol.2023.284192.

  PMID: 37855029 DERIVED

• Raskob GE, van Es N, Verhamme P, Carrier M, Di Nisio M, Garcia D, Grosso MA, Kakkar AK, Kovacs MJ, Mercuri MF, Meyer G, Segers A, Shi M, Wang TF, Yeo E, Zhang G, Zwicker JI, Weitz JI, Buller HR; Hokusai VTE Cancer Investigators. Edoxaban for the Treatment of Cancer-Associated Venous Thromboembolism. N Engl J Med. 2018 Feb 15;378(7):615-624. doi: 10.1056/NEJMoa1711948. Epub 2017 Dec 12.

  PMID: 29231094 DERIVED

• van Es N, Di Nisio M, Bleker SM, Segers A, Mercuri MF, Schwocho L, Kakkar A, Weitz JI, Beyer-Westendorf J, Boda Z, Carrier M, Chlumsky J, Decousus H, Garcia D, Gibbs H, Kamphuisen PW, Monreal M, Ockelford P, Pabinger I, Verhamme P, Grosso MA, Buller HR, Raskob GE. Edoxaban for treatment of venous thromboembolism in patients with cancer. Rationale and design of the Hokusai VTE-cancer study. Thromb Haemost. 2015 Nov 25;114(6):1268-76. doi: 10.1160/TH15-06-0452. Epub 2015 Aug 13.

  PMID: 26271200 DERIVED

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism; Neoplasms

Interventions

edoxaban; Dalteparin; Heparin, Low-Molecular-Weight

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Intervention Hierarchy (Ancestors)

Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates

Results Point of Contact

• Title: Daiichi Sankyo US Contact for Clinical Trial Results
• Organization: Daiichi Sankyo, Inc.

CTRinfo@DSI.com

1-908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2014
• First Posted: February 27, 2014
• Study Start: July 16, 2015
• Primary Completion: September 15, 2017
• Study Completion: September 15, 2017
• Last Updated: March 6, 2019
• Results First Posted: October 24, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

NL (1); HU (1); IT (1); BE (1); US (4); FR (1)