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

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 oncross-sectional or positron emission tomography (PET) imaging, cancer related surgery,chemotherapy or radiation therapy within the past 6 months; note: non-melanoma skincancer 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) oraspartate 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, forwomen of childbearing potential only; note: a women of childbearing potential (WOCBP)is defined as any female who has experienced menarche and who has not undergonesurgical sterilization (hysterectomy or bilateral oophorectomy) and is notpostmenopausal; menopause is defined as 12 months of amenorrhea in a woman over age 45years 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 MonitoringPhase of the study)

Exclusion Criteria:

• Any of the following:

• Pregnant women

• Nursing women

• Men or women of childbearing potential who are unwilling to employ adequatecontraception

• Note: women of child bearing potential must agree to follow instructions formethod(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 instructionsfor 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 activeare exempt from contraceptive requirements; however they must still undergopregnancy testing as described in this section

• Note: investigators shall counsel WOCBP and male subjects who are sexually active withWOCBP on the importance of pregnancy prevention and the implications of an unexpectedpregnancy Investigators shall advise WOCBP and male subjects who are sexually activewith WOCBP on the use of highly effective methods of contraception; highly effectivemethods of contraception have a failure rate of < 1% when used consistently andcorrectly

• At a minimum, subjects must agree to the use of one method of highly effectivecontraception as listed below:

• HIGHLY EFFECTIVE METHODS OF CONTRACEPTION

• Male condoms with spermicide

• Hormonal methods of contraception including combined oral contraceptivepills, 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 hormonebased contraceptives as one of the acceptable methods of contraception sincethey will not be receiving study drug

• IUDs, such as ParaGard

• Tubal ligation

• Vasectomy

• Complete abstinence

• Complete abstinence is defined as complete avoidance of heterosexualintercourse and is an acceptable form of contraception for all studydrugs; female subjects must continue to have pregnancy tests;acceptable alternate methods of highly effective contraception must bediscussed in the event that the subject chooses to forego completeabstinence

• Treatment with an anticoagulant for more than 7 days for the current blood clot, priorto 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 continuedon 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 monthsprior 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 torandomization

• 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