Clinical trial NCT02744092: Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer
Official title: Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer: A Randomized Effectiveness Trial (CANVAS Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cancer
Venous Thromboembolism
Deep Vein Thrombosis (DVT)
Pulmonary Embolism (PE)
Blood Clot
Keywords: Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
Dabigatran (Pradaxa)
Warfarin (Coumadin)
Low molecular weight heparin (LMWH)
Lead sponsor: Alliance Foundation Trials, LLC.
Sponsor class: OTHER
Collaborators: name: Patient-Centered Outcomes Research Institute
First posted: 2016-04-20
Enrollment: 811
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: The overarching objective of the study is to determine the effectiveness of LMWH/ warfarin vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The intervention strategy is Direct Oral AntiCoagulants (DOAC) therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is low molecular weight heparin (LMWH) alone or with warfarin. The information gained will empower cancer patients and physicians to make more informed choices about anticoagulation strategies to manage VTE.

Detailed description: Venous blood clots affect nearly a million Americans each year. Venous clots in the legs are called deep venous thrombosis (DVT) and are dangerous because they travel to the lungs where they cause blockages known as pulmonary emboli (PE). DVT and PE are called venous thromboemboli (VTE). Cancer is a risk factor with nearly 200,000 VTEs in cancer patients each year. The purpose of VTE treatment is to prevent the initial clot from spreading and to prevent new clots from forming. This is accomplished by thinning the blood, or anticoagulation. Without anticoagulation, VTEs recur and are often fatal.

Recently, the FDA has approved 4 new Direct Oral AntiCoagulants (DOACs) for preventing VTE recurrence. Few cancer patients were included in the efficacy trials, and practice guidelines fall silent on whether switching to DOAC therapy is advisable. To fill this knowledge gap, the Alliance Foundation Trials LLC, a research network of academic and community practices across the US, is conducting a pragmatic randomized effectiveness trial.

The overarching objective of the study is to determine the effectiveness of LMWH/ warfarin vs. DOAC anticoagulation for preventing recurrent VTE in cancer patients. The investigators will conduct a trial of 811 cancer patients followed for 6 months. The intervention strategy is DOAC therapy with edoxaban, apixaban, rivaroxaban, or dabigatran. The comparator is LMWH alone or with warfarin. Within each arm, patients can choose the agent they prefer based on side effects, drug interactions, and practical issues such as co-pays. The trial compares these two strategies in terms of treatment: 1) benefits based on VTE recurrence; 2) harms based on bleeding rates; 3) burdens based on patients' reports of their experiences; and 4) mortality rates.

The investigators hypothesize that the benefits, harms and burdens of DOAC treatment will be non-inferior to, or better than, usual care with LMWH/ warfarin among cancer patients. The information gained will empower cancer patients and physicians to make more informed choices about anticoagulation strategies to manage VTE.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of advanced solid tumor cancer, lymphoma, or myeloma (no time restrictions or limitations) -OR- diagnosis of early stage solid tumor cancer, lymphoma, or myeloma \<= 12 months prior to study enrollment
* Diagnosis of VTE \<= 30 days prior to study enrollment for which potential benefits of anticoagulation therapy to prevent recurrence of VTE are felt by the treating physician to exceed the potential harms

  * Any anticoagulation drug/strategy may be used to treat the index VTE; protocol treatment will begin \<= 30days after the index VTE diagnosis date
* Treating physician intends to put participant on anticoagulation therapy for at least three months.
* Age \>= 18 years
* Platelet count is \>= 50,000/mm\^3 (\<= 7 days prior to enrollment)
* CrCl (Creatinine Clearance) is \>= 15 ml/min (\<= 7 days prior to enrollment)

Exclusion Criteria:

* Diagnosis of acute leukemia
* Has ever received or is scheduled to receive an Allogeneic Hematopoietic Stem Cell Transplantation (alloHSCT)

  * Patients who have ever received an Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) ARE eligible.
  * Patients who are scheduled to receive an Autologous Hematopoietic Stem Cell Transplantation (autoHSCT) are NOT eligible
* Ongoing, clinically significant bleeding (CTCAE grade 3 or 4)
* Ongoing therapy with a P-gp inhibitor (e.g., nelfinavir, indinavir, or saquinavir-protease inhibitors for HIV) as these drugs interact with the factor Xa inhibitors
* Therapy with any azole antifungals (e.g., itraconazole, ketaconazole, voriconazole) at the time of enrollment

Primary outcomes:
measure: Cumulative Non-Fatal VTE Recurrence at 6 Months (%)
timeFrame: 6 months
Secondary outcomes:
measure: Cumulative Rates of Major Bleeding
timeFrame: 6 months
measure: Health Related Quality of Life Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire
timeFrame: 3 months
measure: Burden of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire
timeFrame: 3 months
measure: Mortality Reported by Participants' Surrogates (Via Study-specific Questionnaire) or Clinicians (Via Study-specific Case Report Form)
timeFrame: 6 months
measure: Health Related Quality of Life Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire
timeFrame: 6 months
measure: Burden of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire
timeFrame: 6 months
measure: Benefit of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire
timeFrame: 3-months
measure: Benefit of Anticoagulation Therapy Reported by Participants Via the Anti-Clot Treatment Scale (ACTS) Questionnaire
timeFrame: 6-months
measure: Health Related Quality of Life (Mental Health) Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire at 3-months
timeFrame: 3-months
measure: Health Related Quality of Life (Mental Health) Reported by Participants Via the Optum SF-12v2 Health Survey Questionnaire at 6-months
timeFrame: 6-months
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: South County Hematology
state: California
city: Chula Vista
country: United States
facility: Sharp Rees-Stealy
state: California
city: Fremont
country: United States
facility: Washington Hospital Healthcare System
state: California
city: Fremont
country: United States
facility: Washington Hospital
state: California
city: Fresno
country: United States
facility: VA Central California Fresno Medical Center
state: California
city: La Mesa
country: United States
facility: Cancer Center Oncology Medical Group
state: California
city: San Diego
country: United States
facility: Medical Oncology Associates- San Diego
state: California
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: San Diego
country: United States
facility: Sharp Rees-Stealy
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center - Mission Bay
state: California
city: Stockton
country: United States
facility: Saint Joseph's Medical Center
state: California
city: Middletown
country: United States
facility: Middlesex Hospital
state: Connecticut
city: Stamford
country: United States
facility: The Stamford Hospital
state: Connecticut
city: Clearwater
country: United States
facility: Morton Plant Hospital
state: Florida
city: Hollywood
country: United States
facility: Breast Cancer Center at Memorial Regional Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Cancer Institute at Memorial Regional Hospital
state: Florida
city: Hollywood
country: United States
facility: Memorial Regional Hospital
state: Florida
city: Lakeland
country: United States
facility: Hollis Cancer Center
state: Florida
city: Pembroke Pines
country: United States
facility: Breast Cancer Center at Memorial Hospital West
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Cancer Institute at Memorial Hospital West
state: Florida
city: Pembroke Pines
country: United States
facility: Memorial Hospital West
state: Florida
city: Duluth
country: United States
facility: The Center for Cancer Care-Duluth
state: Georgia
city: Lawrenceville
country: United States
facility: Gwinnett Medical Center
state: Georgia
city: Snellville
country: United States
facility: The Center for Cancer Care-Snellville
state: Georgia
city: Honolulu
country: United States
facility: Hawaii Cancer Care POB II
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Oncology Inc POB I
state: Hawaii
city: Honolulu
country: United States
facility: Queen's Medical Center
state: Hawaii
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Cancer Care Liliha
state: Hawaii
city: Honolulu
country: United States
facility: Hawaii Oncology Inc Kuakini
state: Hawaii
city: Post Falls
country: United States
facility: Kootenai Health
state: Idaho
city: Chicago
country: United States
facility: University of Illinois
state: Illinois
city: Chicago
country: United States
facility: Advocate Illinois Masonic Medical Center
state: Illinois
city: Danville
country: United States
facility: Carle on Vermillion
state: Illinois
city: Effingham
country: United States
facility: Carle - Effingham
state: Illinois
city: Evanston
country: United States
facility: NorthShore University HealthSystem Evanston Hospital
state: Illinois
city: Glenview
country: United States
facility: NorthShore University HealthSystem Glenbrook Hospital
state: Illinois
city: Highland Park
country: United States
facility: NorthShore University HealthSystem Highland Park Hospital
state: Illinois
city: Mattoon
country: United States
facility: Carle - Mattoon/Charleston
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center
state: Illinois
city: Skokie
country: United States
facility: NorthShore University HealthSystem Skokie ACC
state: Illinois
city: Urbana
country: United States
facility: The Carle Foundation Hospital/Carle Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Franciscan St. Francis Health - Indianapolis
state: Indiana
city: Michigan City
country: United States
facility: Woodland Cancer Care Center
state: Indiana
city: Mooresville
country: United States
facility: Franciscan St. Francis Health - Mooresville
state: Indiana
city: Richmond
country: United States
facility: Reid Health
state: Indiana
city: South Bend
country: United States
facility: Memorial Hospital at South Bend
state: Indiana
city: Terre Haute
country: United States
facility: Union Hospital
state: Indiana
city: Edgewood
country: United States
facility: Saint Elizabeth Medical Center South
state: Kentucky
city: Fort Thomas
country: United States
facility: Saint Elizabeth Medical Center Fort Thomas
state: Kentucky
city: Lexington
country: United States
facility: Chandler Medical Center - University of Kentucky
state: Kentucky
city: Louisville
country: United States
facility: James Graham Brown Cancer Center
state: Kentucky
city: Louisville
country: United States
facility: Norton Hospital
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Hospital
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville Physicians, PSC
state: Kentucky
city: Louisville
country: United States
facility: University of Louisville, Division of Surgical Oncology
state: Kentucky
city: Bangor
country: United States
facility: Eastern Maine Medical Center
state: Maine
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Bethesda
country: United States
facility: Walter Reed National Military Medical Center
state: Maryland
city: Boston
country: United States
facility: DF/BWCC at Milford Regional Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Brighton
country: United States
facility: St. Elizabeth's Medical Center
state: Massachusetts
city: Lowell
country: United States
facility: Lowell General Hospital
state: Massachusetts
city: South Weymouth
country: United States
facility: South Shore Hospital
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Escanaba
country: United States
facility: Green Bay Oncology, Ltd./St. Francis Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Masonic Cancer Center University of Minnesota Medical Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Health: Clinics and Surgery Center
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Columbia
country: United States
facility: Veterans Administration/Harry S Truman Memorial Hospital
state: Missouri
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center University of Missouri Healthcare
state: Missouri
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - South County
state: Missouri
city: Saint Louis
country: United States
facility: Siteman Cancer Center - West County
state: Missouri
city: Saint Peters
country: United States
facility: Siteman Cancer Center - St. Peters
state: Missouri
city: Anaconda
country: United States
facility: Community Hospital of Anaconda
state: Montana
city: Billings
country: United States
facility: Billings Clinic
state: Montana
city: Billings
country: United States
facility: Montana Cancer Consortium
state: Montana
city: Bozeman
country: United States
facility: Bozeman Health
state: Montana
city: Great Falls
country: United States
facility: Benefis Sletten Cancer Institute
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Las Vegas
country: United States
facility: Nevada Cancer Specialists - Oakey
state: Nevada
city: Las Vegas
country: United States
facility: Ann M Wierman MD LTD
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Specialists - Tenaya
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Cancer Specialists - Fort Apache
state: Nevada
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada - Central Valley
state: Nevada
city: Concord
country: United States
facility: New Hampshire Oncology - Hematology PA
state: New Hampshire
city: Hooksett
country: United States
facility: New Hampshire Oncology-Hematology PA
state: New Hampshire
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Londonderry
country: United States
facility: Dana-Farber/New Hampshire Oncology Hematology
state: New Hampshire
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University Medical Center
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Asheville
country: United States
facility: Mission Hospital - Memorial Campus
state: North Carolina
city: Clinton
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Goldsboro
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Greenville
country: United States
facility: East Carolina University
state: North Carolina
city: Jacksonville
country: United States
facility: Southeastern Medical Oncology Center
state: North Carolina
city: Kenansville
country: United States
facility: Kenansville Medical Center
state: North Carolina
city: Kinston
country: United States
facility: Kinston Medical Specialists, P.A.
state: North Carolina
city: Kinston
country: United States
facility: Lenoir Memorial Hospital
state: North Carolina
city: Richlands
country: United States
facility: Onslow Medical Center
state: North Carolina
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
city: Centerville
country: United States
facility: Dayton Physicians LLC, Miami Valley South
state: Ohio
city: Columbus
country: United States
facility: The James Cancer Hospital and Solove Research Institute
state: Ohio
city: Dayton
country: United States
facility: Dayton Physicians LLC, Samaritan North
state: Ohio
city: Dayton
country: United States
facility: Dayton Clincial Oncology Program
state: Ohio
city: Dayton
country: United States
facility: Veteran Affairs Medical Center
state: Ohio
city: Dayton
country: United States
facility: Wright Patterson Medical Center
state: Ohio
city: Franklin
country: United States
facility: Dayton Physicians LLC, Atrium
state: Ohio
city: Greenville
country: United States
facility: Dayton Physicians, Wayne
state: Ohio
city: Kettering
country: United States
facility: Greater Dayton Cancer Center
state: Ohio
city: Kettering
country: United States
facility: Kettering Medical Center
state: Ohio
city: Maumee
country: United States
facility: Toledo Clinic Cancer Center - Maumee
state: Ohio
city: Toledo
country: United States
facility: Toledo Clinic Cancer Center - Toledo
state: Ohio
city: Troy
country: United States
facility: Dayton Physicians LLC, Upper valley
state: Ohio
city: Ephrata
country: United States
facility: WellSpan Health Ephrata Cancer Center
state: Pennsylvania
city: Gettysburg
country: United States
facility: WellSpan Health Adams Cancer Center
state: Pennsylvania
city: Lebanon
country: United States
facility: WellSpan Health Sechler Family Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Western Pennsylvania Hospital
state: Pennsylvania
city: York
country: United States
facility: WellSpan Health York Cancer Center
state: Pennsylvania
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Fishersville
country: United States
facility: Augusta Health Cancer Center
state: Virginia
city: Fort Belvoir
country: United States
facility: Fort Belvoir Community Hospital
state: Virginia
city: Mechanicsville
country: United States
facility: Bon Secours Cancer Institute Medical Oncology at Memorial Regional
state: Virginia
city: Midlothian
country: United States
facility: Bon Secours Cancer Institute Medical Oncology at St. Francis
state: Virginia
city: Richmond
country: United States
facility: Bon Secours Cancer Institute Medical Oncology at St. Mary's
state: Virginia
city: Auburn
country: United States
facility: MultiCare Regional Cancer Center - Auburn
state: Washington
city: Gig Harbor
country: United States
facility: MultiCare Regional Cancer Center - Gig Harbor Medical Park
state: Washington
city: Puyallup
country: United States
facility: MultiCare Regional Cancer Center - Puyallup
state: Washington
city: Tacoma
country: United States
facility: Multicare Institute for Research & Innovation
state: Washington
city: Tacoma
country: United States
facility: MultiCare Regional Cancer Center - Tacoma
state: Washington
city: Green Bay
country: United States
facility: Green Bay Oncology, Ltd./HSHS St. Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: HSHS St. Vincent Hospital
state: Wisconsin
city: Green Bay
country: United States
facility: Green Bay Oncology, Ltd./HSHS St. Mary's Hospital Medical Center
state: Wisconsin
city: Green Bay
country: United States
facility: HSHS St. Mary's Hospital Medical Center
state: Wisconsin
city: La Crosse
country: United States
facility: Gundersen Lutheran Medical Center
state: Wisconsin
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Oconto Falls
country: United States
facility: Green Bay Oncology, Ltd./HSHS St. Clare Memorial Hospital
state: Wisconsin
city: Sturgeon Bay
country: United States
facility: Green Bay Oncology, Ltd./Door County Memorial Hospital
state: Wisconsin
Study officials:
affiliation: Alliance Foundation Trials, LLC.
name: Deborah Schrag, MD MPH
role: STUDY_CHAIR
affiliation: Alliance Foundation Trials, LLC.
name: Jean Connors, MD
role: STUDY_CHAIR
References:
citation: 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.