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Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer (CANVAS)

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ClinicalTrials.gov Identifier: NCT02744092
Recruitment Status : Recruiting
First Posted : April 20, 2016
Last Update Posted : February 21, 2019
Sponsor:
Collaborator:
Patient-Centered Outcomes Research Institute
Information provided by (Responsible Party):
Alliance Foundation Trials, LLC.

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.

Condition or disease Intervention/treatment Phase
Cancer Venous Thromboembolism Deep Vein Thrombosis (DVT) Pulmonary Embolism (PE) Blood Clot Drug: Rivaroxaban Drug: Apixaban Drug: Edoxaban Drug: Dabigatran Drug: Warfarin Drug: Dalteparin Drug: Enoxaparin Drug: Fondaparinux Not Applicable

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 940 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 940 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Direct Oral Anticoagulants (DOACs) Versus LMWH +/- Warfarin for VTE in Cancer: A Randomized Effectiveness Trial (CANVAS Trial)
Study Start Date : December 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Thinners

Arm Intervention/treatment
Experimental: Randomized Arm 1
Randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC). There are four FDA-approved DOAC drugs that may be used for this study: Rivaroxaban, Apixaban, Edoxaban, or Dabigatran. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.
Drug: Rivaroxaban
Anticoagulation therapy.
Other Name: Xarelto

Drug: Apixaban
Anticoagulation therapy.
Other Name: Eliquis

Drug: Edoxaban
Anticoagulation therapy.
Other Name: Savaysa

Drug: Dabigatran
Anticoagulation therapy.
Other Name: Pradaxa

Active Comparator: Randomized Arm 2
Randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin. There are three FDA-approved LMWH drugs that may be used for this study: Dalteparin, Enoxaparin, or Fondaparinux. The treatment (including dosage form, dosage, frequency and duration) should be administered in accordance with the drug's FDA package insert, and all modifications are at the discretion of the treating investigator.
Drug: Warfarin
Anticoagulation therapy.
Other Name: Coumadin

Drug: Dalteparin
Anticoagulation therapy.
Other Name: Fragmin

Drug: Enoxaparin
Anticoagulation therapy.
Other Name: Lovenox

Drug: Fondaparinux
Anticoagulation therapy.
Other Name: Arixtra

Experimental: Preference Cohort

If an eligible participant is offered randomization and declines randomization, then a limited number of participants (up to N=190) will be allowed to enroll in the Preference Cohort. In this case, the treating physician and patient choose Arm 1 or Arm 2 (non-randomized).

Preference cohort: Non-randomized Arm 1 will get anticoagulation therapy with a Direct Oral AntiCoagulant (DOAC).

Preference cohort: Non-randomized Arm 2 will get anticoagulation therapy with low molecular weight heparin (LMWH) with or without a transition to warfarin.

Drug: Rivaroxaban
Anticoagulation therapy.
Other Name: Xarelto

Drug: Apixaban
Anticoagulation therapy.
Other Name: Eliquis

Drug: Edoxaban
Anticoagulation therapy.
Other Name: Savaysa

Drug: Dabigatran
Anticoagulation therapy.
Other Name: Pradaxa

Drug: Warfarin
Anticoagulation therapy.
Other Name: Coumadin

Drug: Dalteparin
Anticoagulation therapy.
Other Name: Fragmin

Drug: Enoxaparin
Anticoagulation therapy.
Other Name: Lovenox

Drug: Fondaparinux
Anticoagulation therapy.
Other Name: Arixtra




Primary Outcome Measures :
  1. Cumulative VTE recurrence reported by participants (via study-specific questionnaire) or clinicians (via study-specific case report form) [ Time Frame: 6 months ]
    To compare the effectiveness of anticoagulation with a DOAC (intervention) with LMWH/warfarin (comparator) for preventing VTE recurrence in patients with cancer based on cumulative VTE recurrence reported by patients or clinicians at 6 months.


Secondary Outcome Measures :
  1. Cumulative rates of major bleeding reported by participants (via study-specific questionnaire) or clinicians (via study-specific case report form) [ Time Frame: 6 months ]
    To compare the harms of DOAC vs. LMWH/warfarin therapy for cancer patients with VTE based on the cumulative rate of major bleeding at 6 months.

  2. Health related quality of life reported by participants via the Optum SF-12v2 Health Survey questionnaire [ Time Frame: 3 and 6 months ]
    To compare the impact of DOAC vs. LMWH/warfarin therapy on the health related quality of life (HRQOL) for cancer patients with VTE at 3 and 6 months.

  3. Burden of anticoagulation therapy reported by participants via the Anti-Clot Treatment Scale (ACTS) questionnaire [ Time Frame: 3 and 6 months ]
    To compare the burden of anticoagulation therapy with DOAC vs. with LMWH/warfarin for cancer patients with VTE at 3 and 6 months.

  4. Mortality reported by participants' surrogates (via study-specific questionnaire) or clinicians (via study-specific case report form) [ Time Frame: 6 months ]
    To compare the impact of DOAC vs. LMWH/warfarin therapy on mortality in cancer patients with VTE based on survival at 6 months.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 >= 21 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02744092


Contacts
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Contact: Deborah Schrag, MD MPH 617-582-8301 deb_schrag@dfci.harvard.edu
Contact: Jean Connors, MD 617-525-9337 jconnors@partners.org

  Show 146 Study Locations
Sponsors and Collaborators
Alliance Foundation Trials, LLC.
Patient-Centered Outcomes Research Institute
Investigators
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Study Chair: Deborah Schrag, MD MPH Alliance Foundation Trials, LLC.
Study Chair: Jean Connors, MD Alliance Foundation Trials, LLC.

Additional Information:
Study Data/Documents: Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: AFT-28
Email the study team at CANVAS@AllianceFoundationTrials.org.

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Responsible Party: Alliance Foundation Trials, LLC.
ClinicalTrials.gov Identifier: NCT02744092     History of Changes
Other Study ID Numbers: AFT-28
CER-1503-29805 ( Other Grant/Funding Number: Patient-Centered Outcomes Research Institute (PCORI) )
First Posted: April 20, 2016    Key Record Dates
Last Update Posted: February 21, 2019
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Individual-level de-identified datasets will be made available to investigators working under an institution with a Federal Wide Assurance (FWA) who formally submit a request to Alliance Foundation Trials LLC (AFT). Prior to the release of datasets, AFT ensures certain requirements, e.g., IRB approval and data use agreement, are in place. These datasets will be available within 6 months of publication of the manuscript and following a formal request by an investigator to and approval from AFT.

Keywords provided by Alliance Foundation Trials, LLC.:
Rivaroxaban (Xarelto)
Apixaban (Eliquis)
Edoxaban (Savaysa)
Dabigatran (Pradaxa)
Warfarin (Coumadin)
Low molecular weight heparin (LMWH)

Additional relevant MeSH terms:
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Thrombosis
Thromboembolism
Embolism
Venous Thromboembolism
Pulmonary Embolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Heparin
Warfarin
Rivaroxaban
Dabigatran
Apixaban
Heparin, Low-Molecular-Weight
Dalteparin
Edoxaban
Fondaparinux
PENTA
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors