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Apixaban or Dalteparin in Reducing Blood Clots in Patients With Cancer Related Venous Thromboembolism

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ClinicalTrials.gov Identifier: NCT02585713
Recruitment Status : Active, not recruiting
First Posted : October 23, 2015
Last Update Posted : June 7, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Academic and Community Cancer Research United

Brief Summary:

This randomized phase III trial studies the side effects of and compares apixaban and dalteparin in reducing blood clots in patients with cancer-related venous thromboembolism. Venous thromboembolism is a condition in which a blood clot forms in a vein and then breaks off and moves through the bloodstream. Patients with cancer are at increased risk for venous thromboembolism. Apixaban and dalteparin are drugs used to prevent blood clots from forming or to treat blood clots that have formed. It is not yet known whether apixaban or dalteparin is more effective in reducing blood clots in patients with cancer related venous thromboembolism.

ADAM-VTE


Condition or disease Intervention/treatment Phase
Cerebral Vein Thrombosis Deep Vein Thrombosis Gonadal Thrombosis Hepatic Thrombosis Malignant Neoplasm Mesenteric Thrombosis Metastatic Malignant Neoplasm Portal Vein Thrombosis Pulmonary Embolism Renal Vein Thrombosis Splenic Thrombosis Venous Thromboembolism Drug: Apixaban Drug: Dalteparin Other: Questionnaire Administration Phase 3

Detailed Description:

PRIMARY OBJECTIVES:

I. Any episode of major bleeding including fatal bleeding.

SECONDARY OBJECTIVES:

I. Venous thromboembolism (VTE) recurrence including deep vein thrombosis (DVT), pulmonary embolism (PE), fatal PE, or arterial thromboembolism.

II. Any episode of major bleeding including fatal bleeding or any episode of clinically relevant non-major bleeding.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive apixaban 10 mg orally (PO) twice daily (BID) on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.

ARM II: Patients receive dalteparin 200 international units (IU)/kg/day subcutaneously (SC) once daily (QD) on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.

After completion of study treatment, patients are followed up at 3 months.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 315 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: A Phase III, Randomized, Open Label Study Evaluating the Safety of Apixaban in Subjects With Cancer Related Venous Thromboembolism
Actual Study Start Date : November 20, 2015
Actual Primary Completion Date : April 2, 2018
Estimated Study Completion Date : November 20, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Blood Clots
Drug Information available for: Apixaban

Arm Intervention/treatment
Experimental: Arm I (apixaban)
Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.
Drug: Apixaban
Given PO
Other Names:
  • BMS-562247
  • BMS-562247-01
  • Eliquis

Other: Questionnaire Administration
Ancillary studies

Experimental: Arm II (dalteparin)
Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.
Drug: Dalteparin
Given SC

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Episode of major bleeding including fatal bleeding [ Time Frame: Up to 7 days after treatment termination ]
    Patients will be analyzed according to the drug they received. Major bleeding events observed after 7 days will be described separately. The frequency of major bleeding events will be summarized separately by treatment arm. The cumulative incidence of major bleeding at 6 months from treatment initiation and its associated 95% confidence interval will be estimated separately by treatment arm using a cumulative incidence function, treating death without bleeding as a competing risk. A Cox proportional hazard model will be used to determine the point estimate for the hazard ratio (comparing apixa


Secondary Outcome Measures :
  1. Incidence of bleeding event defined as a major bleed or a clinically relevant non-major bleed [ Time Frame: Up to 7 days after treatment termination ]
    A similar analysis as described for the primary safety analysis will be used. The impact of baseline covariates on the safety outcome will be explored by adjusting for them in the Cox models. The frequencies of the separate components contributing to the safety outcome will be described. Incidence of adverse events will be coded using the MedDRA Dictionary.

  2. Time to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) [ Time Frame: Up to 3 months post-treatment ]
    Analyzed using the same methods described above for the primary endpoint. The impact of baseline covariates (location of DVT, renal clearance, age, sex, mobility at randomization, pulmonary disease, and cardiac disease) on the efficacy outcome will be explored adjusting for them in the Cox models. There is no adjustment for multiple comparisons. This analysis will be conducted at the one-sided type I error of 0.05. The assumption of proportional hazards will be checked for all Cox models (including primary and secondary endpoints) using graphical methods as log(-log)-plots and plots of scaled



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed acute lower extremity or upper extremity (jugular, innominate, subclavian, axillary, brachial) DVT, PE, splanchnic (hepatic, portal, splenic, mesenteric, renal, gonadal), or cerebral vein thrombosis
  • Active cancer defined as metastatic disease and/or any evidence of cancer on cross-sectional or positron emission tomography (PET) imaging, cancer related surgery, chemotherapy or radiation therapy within the past 6 months; note: non-melanoma skin cancer does not meet the cancer requirement
  • Life expectancy >= 60 days
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
  • Obtained =< 30 days prior to randomization: Platelet count >= 50,000/mm^3
  • Obtained =< 30 days prior to randomization: Alanine aminotransferase (ALT) or aspartate transaminase (AST) =< 3 x upper limit of normal (ULN)
  • Obtained =< 30 days prior to randomization: International normalized ratio (INR) =< 1.6 (if not taking anticoagulant therapy)
  • Obtained =< 30 days prior to randomization: Calculated creatinine clearance must be >= 30 ml/min using the Cockcroft-Gault formula
  • Negative serum or urine pregnancy test done =< 24 hours prior to randomization, for women of childbearing potential only; note: a women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal; menopause is defined as 12 months of amenorrhea in a woman over age 45 years in the absence of other biological or physiological causes
  • Ability to complete questionnaire(s) by themselves or with assistance
  • Ability to provide informed written consent
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

Exclusion Criteria:

  • Any of the following:

    • Pregnant women
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception

      • Note: women of child bearing potential must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 33 days after finishing the last dose
      • Males who are sexually active with WOCBP must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug (s) plus 93 days after finishing the last dose
      • Azoospermic males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements; however they must still undergo pregnancy testing as described in this section
  • Note: investigators shall counsel WOCBP and male subjects who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy Investigators shall advise WOCBP and male subjects who are sexually active with WOCBP on the use of highly effective methods of contraception; highly effective methods of contraception have a failure rate of < 1% when used consistently and correctly
  • At a minimum, subjects must agree to the use of one method of highly effective contraception as listed below:

    • HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

      • Male condoms with spermicide
      • Hormonal methods of contraception including combined oral contraceptive pills, vaginal ring, injectables, implants and intrauterine devices (IUDs) such as Mirena by WOCBP subject or male subject?s WOCBP partner
      • Female partners of male subjects participating in the study may use hormone based contraceptives as one of the acceptable methods of contraception since they will not be receiving study drug
      • IUDs, such as ParaGard
      • Tubal ligation
      • Vasectomy
      • Complete abstinence

        • Complete abstinence is defined as complete avoidance of heterosexual intercourse and is an acceptable form of contraception for all study drugs; female subjects must continue to have pregnancy tests; acceptable alternate methods of highly effective contraception must be discussed in the event that the subject chooses to forego complete abstinence
  • Treatment with an anticoagulant for more than 7 days for the current blood clot, prior to randomization
  • Active bleeding
  • Severe hypersensitivity reaction to apixaban, dalteparin, heparin or pork products (e.g., anaphylactic reactions)
  • Use of the following CYP3A4 inducers: rifampin, rifabutin, carbamazepine, efavirenz, phenobarbital, phenytoin, fosphenytoin, primidone, and St. John?s wort)
  • Thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) that will be continued on study
  • Severe liver disease (known cirrhosis Childs Pugh class B or C), or active hepatitis
  • Use of a Factor Xa inhibitor (e.g. apixaban, rivaroxaban, or edoxaban) =< 3 months prior to randomization
  • Treatment of a thromboembolic event =< 6 months prior to randomization
  • Documented venous thromboembolism while on therapeutic anticoagulation (?anticoagulation failure?)
  • Mechanical heart valve
  • Documented hemorrhagic tendencies
  • Bacterial endocarditis
  • History of heparin induced thrombocytopenia
  • Any of the following conditions:

    • Intracranial bleeding =< 6 months prior to randomization
    • Intraocular bleeding =< 6 months prior to randomization
    • Gastrointestinal bleeding and/or endoscopically proven ulcer =< 6 months prior to randomization
    • Head trauma or major trauma =<1 month prior to randomization
    • Neurosurgery =< 2 weeks prior to randomization
    • Major surgery =< 1 week prior to randomization
    • Overt major bleeding at the time of randomization
    • Gross hematuria at the time of randomization

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): NCT02585713


Locations
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United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, Florida
Mayo Clinic in Florida
Jacksonville, Florida, United States, 32224-9980
United States, Illinois
NorthShore University HealthSystem-Evanston Hospital
Evanston, Illinois, United States, 60201
Illinois CancerCare-Peoria
Peoria, Illinois, United States, 61615
United States, Iowa
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, United States, 52242
Siouxland Regional Cancer Center
Sioux City, Iowa, United States, 51101
United States, Kansas
Cancer Center of Kansas - Wichita
Wichita, Kansas, United States, 67214
United States, Michigan
Cancer Research Consortium of West Michigan NCORP
Grand Rapids, Michigan, United States, 49503
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Coborn Cancer Center at Saint Cloud Hospital
Saint Cloud, Minnesota, United States, 56303
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, United States, 55416
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198
United States, New Hampshire
New Hampshire Oncology Hematology PA-Hooksett
Hooksett, New Hampshire, United States, 03106
United States, North Carolina
FirstHealth of the Carolinas-Moore Regional Hosiptal
Pinehurst, North Carolina, United States, 28374
United States, Ohio
Columbus NCI Community Oncology Research Program
Columbus, Ohio, United States, 43215
Toledo Clinic Cancer Centers-Toledo
Toledo, Ohio, United States, 43623
United States, Pennsylvania
Guthrie Medical Group PC-Robert Packer Hospital
Sayre, Pennsylvania, United States, 18840
United States, South Dakota
Rapid City Regional Hospital
Rapid City, South Dakota, United States, 57701
Sponsors and Collaborators
Academic and Community Cancer Research United
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Robert McBane Academic and Community Cancer Research United

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Academic and Community Cancer Research United
ClinicalTrials.gov Identifier: NCT02585713     History of Changes
Other Study ID Numbers: RU221501I
NCI-2015-01573 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CV185-444
RU221501I ( Other Identifier: Academic and Community Cancer Research United )
P30CA015083 ( U.S. NIH Grant/Contract )
First Posted: October 23, 2015    Key Record Dates
Last Update Posted: June 7, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

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