Apixaban in Preventing Secondary Cancer Related Venous Thrombosis in Cancer Patients Who Have Completed Anticoagulation Therapy

Pulmonary Embolism Clinical Trial

Official title:

A Phase III, Randomized, Controlled, Double-Blind Study Evaluating the Safety of Two Doses of Apixaban for Secondary Prevention of Cancer Related Venous Thrombosis in Subjects Who Have Completed at Least Six Months of Anticoagulation Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03080883
• Other study ID #: ACCRU-SC-1601
• Secondary ID: NCI-2017-00325AC
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: July 14, 2017
• Est. completion date: May 31, 2025

Study information

• Verified date: May 2023
• Source: Academic and Community Cancer Research United
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVE: I. Any episode of major bleeding including fatal bleeding or clinically relevant non-major bleeding. SECONDARY OBJECTIVES: I. The proportion of patients who experienced at least one such bleeding event within 6 months of beginning treatment. II. Venous thromboembolism (VTE) recurrence including deep vein thrombosis (DVT), pulmonary embolism (PE), fatal PE, or arterial thromboembolism. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive lower dose apixaban orally (PO) twice daily (BID) for 365 days. GROUP II: Patients receive higher dose apixaban PO BID for 365 days. After completion of study treatment, patients are followed up for 30 days.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 370
• Est. completion date: May 31, 2025
• Est. primary completion date: June 7, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Vein Thrombosis
• Deep Vein Thrombosis
• Embolism
• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Metastatic Malignant Solid Neoplasm
• Neoplasms
• Pulmonary Embolism
• Splanchnic Vein Thrombosis
• Thrombosis
• Venous Thrombosis

Intervention

Drug:
• Apixaban
Given PO

Locations

Country	Name	City	State
United States	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	UNC Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	Duke University Medical Center	Durham	North Carolina
United States	Mayo Clinic Health System-Eau Claire Clinic	Eau Claire	Wisconsin
United States	Saint Elizabeth Medical Center South	Edgewood	Kentucky
United States	NorthShore University HealthSystem-Evanston Hospital	Evanston	Illinois
United States	Altru Cancer Center	Grand Forks	North Dakota
United States	New Hampshire Oncology Hematology PA-Hooksett	Hooksett	New Hampshire
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Mayo Clinic in Florida	Jacksonville	Florida
United States	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire
United States	Dean Hematology and Oncology Clinic	Madison	Wisconsin
United States	Solinsky Center for Cancer Care	Manchester	New Hampshire
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Froedtert and the Medical College of Wisconsin LAPS	Milwaukee	Wisconsin
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	FirstHealth of the Carolinas-Moore Regional Hospital	Pinehurst	North Carolina
United States	Mayo Clinic in Rochester	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Metro Minnesota Community Oncology Research Consortium	Saint Louis Park	Minnesota
United States	Mayo Clinic in Arizona	Scottsdale	Arizona
United States	University of Washington Medical Center - Montlake	Seattle	Washington
United States	Carle Cancer Center	Urbana	Illinois
United States	MedStar Georgetown University Hospital	Washington	District of Columbia
United States	Cleveland Clinic-Weston	Weston	Florida
United States	Cancer Center of Kansas - Wichita	Wichita	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Academic and Community Cancer Research United	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CIF of Major or Clinically Relevant Non-major Bleeding Combined With Death as Competing Risk	Incidence of major bleeding and clinically relevant non-major bleeding will be estimated using the cumulative incidence function (CIF) with death without major bleeding or clinically relevant non-major bleeding and with adverse events that results in termination of treatment (including vascular events) as competing risks. The time to event is defined as the time from randomization to the first occurrence of a major bleeding, a clinically relevant non-major bleeding, death without major bleeding or clinically relevant non-major bleeding, or an adverse event that results in termination of treatment. Patients who were lost to follow-up, who withdrew informed consent before the end of the predefined study duration will be censored at the last day the patient had a complete assessment for study outcomes within the intended study period. The difference in the incidences of the combined endpoint at 12 months between treatment arms will be estimated along with a 95% confidence interval	12 months
Secondary	Proportion of Patients Who Experienced at Least One Bleeding Event	Incidence of major bleeding and clinically relevant non-major bleeding will be estimated using the cumulative incidence function (CIF) with death without major bleeding or clinically relevant non-major bleeding and with adverse events that results in termination of treatment (including vascular events) as competing risks. The time to event is defined as the time from randomization to the first occurrence of a major bleeding, a clinically relevant non-major bleeding, death without major bleeding or clinically relevant non-major bleeding, or an adverse event that results in termination of treatment. Patients who were lost to follow-up, who withdrew informed consent before the end of the predefined study duration will be censored at the last day the patient had a complete assessment for study outcomes within the intended study period. The difference in the incidences of the combined endpoint at 6 months between treatment arms will be estimated along with a 95% confidence interval.	6 months
Secondary	Cumulative Incidence Function of DVT/PE Treating Death or AE Resulting in End of Treatment as Competing Risk by Study Arm	For the secondary outcome analysis, the time from starting treatment to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) outcome will be analyzed using the same method described in the section for primary outcome plan. For this outcome, death without DVT/PE and adverse events leading to termination of treatment will be treated as the competing risks.	12 months