Cancer Venous Thromboembolism (VTE)

• ClinicalTrials.gov Identifier: NCT02073682
• Recruitment Status: Completed
• First Posted: February 27, 2014
• Results First Posted: October 24, 2018
• Last Update Posted: March 6, 2019
• Sponsor: Daiichi Sankyo, Inc.
• Information provided by (Responsible Party): Daiichi Sankyo, Inc.

Tracking Information

• First Submitted Date: February 25, 2014
• First Posted Date: February 27, 2014
• Results First Submitted Date: September 26, 2018
• Results First Posted Date: October 24, 2018
• Last Update Posted Date: March 6, 2019
• Actual Study Start Date: July 16, 2015
• Actual Primary Completion Date: September 15, 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: September 26, 2018): Number of Participants With Adjudicated Recurrent Venous Thromboembolism (VTE) or Major Bleeding Event [ Time Frame: 12 months ]

Original Primary Outcome Measures (submitted: February 25, 2014)

• incidence of recurrent VTE at end of study [ Time Frame: 6 months ]
  primary efficacy outcome is incidence of recurrent VTE at end of study
• incidence of of clinically relevant bleeding while on treatment [ Time Frame: 6 months ]
  primary safety outcome is incidence of clinically relevant bleeding while on treatment

Current Secondary Outcome Measures (submitted: September 26, 2018)

• Number of Participants With Adjudicated Major Bleeding Events While on Treatment [ Time Frame: 12 months ]
  The primary safety endpoint was major bleeding events during the On-Treatment Study Period (defined as on-study drug or up to 3 days after the last dose of study drug).
• Number of Participants With Recurrent Venous Thromboembolism (VTE) During the Overall Study Period [ Time Frame: 12 months ]
• Number of Participants With Recurrent Deep Vein Thrombosis (DVT) During the Overall Study Period [ Time Frame: 12 months ]
• Number of Participants With Recurrent Non-Fatal Pulmonary Embolism (PE) During the Overall Study Period [ Time Frame: 12 months ]
• Number of Participants With VTE-Related Death [ Time Frame: 12 months ]
• Number of Participants With Recurrent VTE, Major Bleed or All-Cause Death [ Time Frame: 12 months ]

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cancer Venous Thromboembolism (VTE)
• Official Title: A Phase 3b, Prospective, Randomized, Open-label, Blind Evaluator (PROBE) Study Evaluating the Efficacy and Safety of (LMW) Heparin/Edoxaban Versus Dalteparin in Venous Thromboembolism Associated With Cancer
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: Edoxaban
  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.
  Other Name: DU-176b
• Drug: Dalteparin
  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.
  Other Name: Active comparator
• Drug: Low molecular weight heparin
  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.
  Other Name: LMWH

Study Arms

• Experimental: Edoxaban group
  After 5 days of low molecular weight heparin (LMWH), patients receive edoxaban treatment daily - tablet for oral use
  Interventions:

  • Drug: Edoxaban
  • Drug: Low molecular weight heparin
• Active Comparator: Dalteparin group
  Participants receive Dalteparin treatment daily -solution for subcutaneous injection
  Intervention: Drug: Dalteparin

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 26, 2018): 1046
• Original Enrollment: Not Provided
• Actual Study Completion Date: September 15, 2017
• Actual Primary Completion Date: September 15, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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;

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Hungary, Italy, Netherlands, United States

Administrative Information

• NCT Number: NCT02073682
• Other Study ID Numbers: DU176b-D-U311; 2014-004708-30 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (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.
• URL: https://vivli.org/ourmember/daiichi-sankyo/

• Current Responsible Party: Daiichi Sankyo, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Daiichi Sankyo, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Global Clinical Leader; Daiichi Sankyo, Inc.

• PRS Account: Daiichi Sankyo, Inc.
• Verification Date: September 2018