Apixaban in Preventing Secondary Cancer Related Venous Thrombosis in Cancer Patients Who Have Completed Anticoagulation Therapy
Condition: Cerebral Vein Thrombosis; Deep Vein Thrombosis; Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Pulmonary Embolism; Splanchnic Vein Thrombosis
MeSH terms: Neoplasms; Pulmonary Embolism; Thrombosis; Embolism; Venous Thrombosis
Intervention: Apixaban
Intervention description: Given PO
Intervention MeSH terms: Apixaban
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 370.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies the best dose of apixaban and how well it works in
      preventing secondary cancer related venous thrombosis in cancer patients who have completed
      anticoagulation therapy. Apixaban may help in prevention by blocking some of the enzymes
      needed for venous thrombosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Confirmed acute index (original venous thrombotic) event: lower extremity or upper
             extremity (jugular, innominate, subclavian, axillary, brachial) DVT, PE, splanchnic
             (hepatic, portal, splenic, mesenteric, renal, gonadal), or cerebral vein thrombosis
             for which the patient has received >= 180 days (but =< 365 days) of anticoagulant
             therapy prior to registration; the date, imaging modality, and location of index event
             will be required; the date of initiation and specific type of anticoagulants used will
             also be required

          -  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 >= 6 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2

          -  Hemoglobin >= 8 g/dL obtained =< 30 days prior to registration

          -  Platelet count >= 50,000/mm^3 obtained =< 30 days prior to registration

          -  Alanine aminotransferase (ALT) or aspartate transaminase (AST) =< 3 x upper limit of
             normal (ULN) obtained =< 30 days prior to registration

          -  Calculated creatinine clearance must be >= 30 ml/min using the Cockcroft-Gault formula
             obtained =< 30 days prior to registration

          -  Negative serum or urine pregnancy test done =< 7 days prior to registration, for women
             of childbearing potential only;

               -  Note: a woman 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 provide informed written consent

          -  Willing to undergo monthly follow-up assessment, either in person at the enrolling
             institution or by telephone

        Exclusion Criteria:

          -  Any of the following because this study involves an investigational agent whose
             genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are
             unknown:

               -  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:

                         -  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

                         -  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; acceptable alternate methods of
                                 highly effective contraception must be discussed in the event that
                                 the subject chooses to forego complete abstinence

          -  Active major bleeding

          -  Severe hypersensitivity reaction to apixaban (e.g., anaphylactic reactions)

          -  Current use of strong CYP3A4 inducers or inhibitors

               -  NOTE: patients may be eligible if they transition to an alternative agent or are
                  able to stop CYP3A4 inducer or inhibitor

          -  Current use of 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

          -  Documented venous thromboembolism while on therapeutic anticoagulation
             ("anticoagulation failure")

          -  Mechanical heart valve

          -  Documented hemorrhagic tendencies (e.g., hemophilia)

          -  Bacterial endocarditis

          -  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

               -  Gross hematuria at the time of randomization