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Cerebral Vein ThrombosisPhase 3NCT03080883

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

A Phase 3 study testing Apixaban in people with Cerebral Vein Thrombosis and Deep Vein Thrombosis, run by Academic and Community Cancer Research United at 32 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Apixaban
Could I receive a placebo?
No, everyone receives an active treatment
How many people
370 participants
Where
32 sitesUnited States
Study dates
14 Jul 2017to 9 May 2025
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

32 sites in 1 country.

32 sites in 1 country

United States32 sites

  • University of Michigan Comprehensive Cancer Center

    Ann Arbor, Michigan, 48109

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Northwestern University

    Chicago, Illinois, 60611

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Mayo Clinic Health System-Eau Claire Clinic

    Eau Claire, Wisconsin, 54701

  • Saint Elizabeth Medical Center South

    Edgewood, Kentucky, 41017

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Altru Cancer Center

    Grand Forks, North Dakota, 58201

  • New Hampshire Oncology Hematology PA-Hooksett

    Hooksett, New Hampshire, 03106

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Dartmouth Hitchcock Medical Center

    Lebanon, New Hampshire, 03756

  • Dean Hematology and Oncology Clinic

    Madison, Wisconsin, 53717

  • Solinsky Center for Cancer Care

    Manchester, New Hampshire, 03103

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Froedtert and the Medical College of Wisconsin LAPS

    Milwaukee, Wisconsin, 53226

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • Illinois CancerCare-Peoria

    Peoria, Illinois, 61615

  • FirstHealth of the Carolinas-Moore Regional Hospital

    Pinehurst, North Carolina, 28374

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Montefiore Medical Center - Moses Campus

    The Bronx, New York, 10467

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

  • Cleveland Clinic-Weston

    Weston, Florida, 33331

  • Cancer Center of Kansas - Wichita

    Wichita, Kansas, 67214

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. Any episode of major bleeding including fatal bleeding or clinically relevant non-major bleeding.

SECONDARY OBJECTIVES:

  1. 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.

Being tested
Apixaban
Medical subject headings
Intracranial Thrombosis, Venous Thrombosis, Hematologic Neoplasms, Neoplasm Metastasis, Pulmonary Embolism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ApixabanDrug

    Also called BMS-562247, BMS-562247-01, Eliquis

    Given PO

Study groups in NCT03080883
Study groupRoleWhat they receive
Group I (lower dose apixaban)ExperimentalPatients receive lower dose apixaban PO BID for 365 days.
Receives: Drug: Apixaban
Group II (higher dose apixaban)ExperimentalPatients receive higher dose apixaban PO BID for 365 days.
Receives: Drug: Apixaban

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 12 months

Secondary outcomes (2)

  1. 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.

    Measured: 6 months

  2. 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.

    Measured: 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Mar 2017
  2. Study start14 Jul 2017
  3. Primary completion7 Jun 2022
  4. Study completion9 May 2025

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
370 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03080883
Sponsor's protocol ID
ACCRU-SC-1601
Other IDs
NCI-2017-00325, ACCRU-SC-1601, P30CA015083
Status last verified
May 2025
First submitted
10 Mar 2017
Last updated
18 May 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • McBane RD 2nd, Loprinzi CL, Zemla T, Tafur A, Sanfilippo K, Liu JJ, Garcia DA, Heun J, Gundabolu K, Onitilo AA, Perepu U, Drescher MR, Henkin S, Houghton D, Ashrani A, Billett H, McCue SA, Lee MK, Le-Rademacher JG, Wysokinski WE; EVE trial investigators. Extending venous thromboembolism secondary prevention with apixaban in cancer patients. The EVE trial. J Thromb Haemost. 2024 Jun;22(6):1704-1714. doi: 10.1016/j.jtha.2024.03.011. Epub 2024 Mar 25.

    PubMed 38537780

  • 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.

    PubMed 31606897

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Apixaban in people with Cerebral Vein Thrombosis and Deep Vein Thrombosis, run by Academic and Community Cancer Research United at 32 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 32 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

CIF of Major or Clinically Relevant Non-major Bleeding Combined With Death as Competing Risk (time frame: 12 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03080883, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2025.

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