search
Back to results

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

Primary Purpose

Cerebral Vein Thrombosis, Deep Vein Thrombosis, Hematopoietic and Lymphoid Cell Neoplasm

Status
Active
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Apixaban
Sponsored by
Academic and Community Cancer Research United
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cerebral Vein Thrombosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Arizona
  • MedStar Georgetown University Hospital
  • Mayo Clinic in Florida
  • Cleveland Clinic-Weston
  • Northwestern University
  • NorthShore University HealthSystem-Evanston Hospital
  • Illinois CancerCare-Peoria
  • Carle Cancer Center
  • University of Iowa/Holden Comprehensive Cancer Center
  • Cancer Center of Kansas - Wichita
  • Saint Elizabeth Medical Center South
  • Dana-Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • Mayo Clinic in Rochester
  • Metro Minnesota Community Oncology Research Consortium
  • Washington University School of Medicine
  • University of Nebraska Medical Center
  • New Hampshire Oncology Hematology PA-Hooksett
  • Dartmouth Hitchcock Medical Center
  • Solinsky Center for Cancer Care
  • Montefiore Medical Center - Moses Campus
  • UNC Lineberger Comprehensive Cancer Center
  • University of North Carolina
  • Duke University Medical Center
  • FirstHealth of the Carolinas-Moore Regional Hospital
  • Altru Cancer Center
  • University of Washington Medical Center - Montlake
  • Mayo Clinic Health System-Eau Claire Clinic
  • Dean Hematology and Oncology Clinic
  • Marshfield Medical Center-Marshfield
  • Froedtert and the Medical College of Wisconsin LAPS
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Group I (lower dose apixaban)

Group II (higher dose apixaban)

Arm Description

Patients receive lower dose apixaban PO BID for 365 days.

Patients receive higher dose apixaban PO BID for 365 days.

Outcomes

Primary Outcome Measures

Proportion of patients who experience at least one bleeding event
Patients will be analyzed according to the drug they received. The analysis of major bleeding plus clinically relevant nonmajor bleeding events will primarily focus on those events which occurred during treatment or within 7 days of treatment discontinuation. Major bleeding events observed later will be described separately. The difference in the incidences of the combined endpoint at 6 months and at 12 months between treatment arms will be estimated along with a 95% confidence interval.

Secondary Outcome Measures

Proportion of patients who experienced at least one bleeding event
Will estimate the difference in proportion of patients who experience at least one bleeding event (i.e. the primary endpoint) within 6 months of beginning treatment across the two study arms. As with the primary analysis, a 95% confidence interval will be calculated for the difference between arms.
Venous thromboembolism recurrence
The time to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) outcome will be analyzed.

Full Information

First Posted
March 10, 2017
Last Updated
May 11, 2023
Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT03080883
Brief Title
Apixaban in Preventing Secondary Cancer Related Venous Thrombosis in Cancer Patients Who Have Completed Anticoagulation Therapy
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
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 14, 2017 (Actual)
Primary Completion Date
June 7, 2022 (Actual)
Study Completion Date
May 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Academic and Community Cancer Research United
Collaborators
National Cancer Institute (NCI)

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cerebral Vein Thrombosis, Deep Vein Thrombosis, Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Metastatic Malignant Solid Neoplasm, Pulmonary Embolism, Splanchnic Vein Thrombosis

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
370 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Group I (lower dose apixaban)
Arm Type
Experimental
Arm Description
Patients receive lower dose apixaban PO BID for 365 days.
Arm Title
Group II (higher dose apixaban)
Arm Type
Experimental
Arm Description
Patients receive higher dose apixaban PO BID for 365 days.
Intervention Type
Drug
Intervention Name(s)
Apixaban
Other Intervention Name(s)
BMS-562247, BMS-562247-01, Eliquis
Intervention Description
Given PO
Primary Outcome Measure Information:
Title
Proportion of patients who experience at least one bleeding event
Description
Patients will be analyzed according to the drug they received. The analysis of major bleeding plus clinically relevant nonmajor bleeding events will primarily focus on those events which occurred during treatment or within 7 days of treatment discontinuation. Major bleeding events observed later will be described separately. The difference in the incidences of the combined endpoint at 6 months and at 12 months between treatment arms will be estimated along with a 95% confidence interval.
Time Frame
Up to 12 months
Secondary Outcome Measure Information:
Title
Proportion of patients who experienced at least one bleeding event
Description
Will estimate the difference in proportion of patients who experience at least one bleeding event (i.e. the primary endpoint) within 6 months of beginning treatment across the two study arms. As with the primary analysis, a 95% confidence interval will be calculated for the difference between arms.
Time Frame
Up to 6 months
Title
Venous thromboembolism recurrence
Description
The time to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) outcome will be analyzed.
Time Frame
Up to 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert D McBane
Organizational Affiliation
Academic and Community Cancer Research United
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Mayo Clinic in Florida
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32224-9980
Country
United States
Facility Name
Cleveland Clinic-Weston
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
NorthShore University HealthSystem-Evanston Hospital
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60201
Country
United States
Facility Name
Illinois CancerCare-Peoria
City
Peoria
State/Province
Illinois
ZIP/Postal Code
61615
Country
United States
Facility Name
Carle Cancer Center
City
Urbana
State/Province
Illinois
ZIP/Postal Code
61801
Country
United States
Facility Name
University of Iowa/Holden Comprehensive Cancer Center
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Cancer Center of Kansas - Wichita
City
Wichita
State/Province
Kansas
ZIP/Postal Code
67214
Country
United States
Facility Name
Saint Elizabeth Medical Center South
City
Edgewood
State/Province
Kentucky
ZIP/Postal Code
41017
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Metro Minnesota Community Oncology Research Consortium
City
Saint Louis Park
State/Province
Minnesota
ZIP/Postal Code
55416
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
University of Nebraska Medical Center
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68198
Country
United States
Facility Name
New Hampshire Oncology Hematology PA-Hooksett
City
Hooksett
State/Province
New Hampshire
ZIP/Postal Code
03106
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
Solinsky Center for Cancer Care
City
Manchester
State/Province
New Hampshire
ZIP/Postal Code
03103
Country
United States
Facility Name
Montefiore Medical Center - Moses Campus
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
UNC Lineberger Comprehensive Cancer Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
FirstHealth of the Carolinas-Moore Regional Hospital
City
Pinehurst
State/Province
North Carolina
ZIP/Postal Code
28374
Country
United States
Facility Name
Altru Cancer Center
City
Grand Forks
State/Province
North Dakota
ZIP/Postal Code
58201
Country
United States
Facility Name
University of Washington Medical Center - Montlake
City
Seattle
State/Province
Washington
ZIP/Postal Code
98195
Country
United States
Facility Name
Mayo Clinic Health System-Eau Claire Clinic
City
Eau Claire
State/Province
Wisconsin
ZIP/Postal Code
54701
Country
United States
Facility Name
Dean Hematology and Oncology Clinic
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53717
Country
United States
Facility Name
Marshfield Medical Center-Marshfield
City
Marshfield
State/Province
Wisconsin
ZIP/Postal Code
54449
Country
United States
Facility Name
Froedtert and the Medical College of Wisconsin LAPS
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
31606897
Citation
McBane RD 2nd, Loprinzi CL, Ashrani A, Lenz CJ, Houghton D, Zemla T, Le-Rademacher JG, Wysokinski WE. Extending venous thromboembolism secondary prevention with apixaban in cancer patients: The EVE trial. Eur J Haematol. 2020 Feb;104(2):88-96. doi: 10.1111/ejh.13338. Epub 2019 Nov 11.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs