Apixaban or Dalteparin in Reducing Blood Clots in Patients With Cancer Related Venous Thromboembolism
Condition: 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
MeSH terms: Neoplasms; Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Venous Thrombosis
Intervention: Apixaban; Dalteparin; Questionnaire Administration
Intervention description: Given PO; Given SC; Ancillary studies
Intervention MeSH terms: Dalteparin; Tinzaparin; Heparin, Low-Molecular-Weight; Apixaban
Phase: Phase 3
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 300.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility 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