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

NCT03080883 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: ACCRU-SC-1601NCI-2017-00325P30CA015083
• Study Type: interventional
• Target: 370
• Locations: 1 country
• Sites: 32

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.

Conditions

Cerebral Vein Thrombosis; Deep Vein Thrombosis; Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Metastatic Malignant Solid Neoplasm; Pulmonary Embolism; Splanchnic Vein Thrombosis

Outcome Measures

Primary Outcomes (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

  12 months

Secondary Outcomes (2)

• Proportion of Patients Who Experienced at Least One Bleeding Event

  6 months

• Cumulative Incidence Function of DVT/PE Treating Death or AE Resulting in End of Treatment as Competing Risk by Study Arm

  12 months

Study Arms (2)

Group I (lower dose apixaban)

EXPERIMENTAL

Patients receive lower dose apixaban PO BID for 365 days.

Drug: Apixaban

Group II (higher dose apixaban)

EXPERIMENTAL

Patients receive higher dose apixaban PO BID for 365 days.

Drug: Apixaban

Interventions

Apixaban DRUG

Given PO

Also known as: BMS-562247, BMS-562247-01, Eliquis

Group I (lower dose apixaban); Group II (higher dose apixaban)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Academic and Community Cancer Research United: lead
• National Cancer Institute (NCI): collaborator

Study Sites (32)

Mayo Clinic in Arizona

Scottsdale, Arizona, 85259, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Cleveland Clinic-Weston

Weston, Florida, 33331, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

NorthShore University HealthSystem-Evanston Hospital

Evanston, Illinois, 60201, United States

Location

Illinois CancerCare-Peoria

Peoria, Illinois, 61615, United States

Location

Carle Cancer Center

Urbana, Illinois, 61801, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Cancer Center of Kansas - Wichita

Wichita, Kansas, 67214, United States

Location

Saint Elizabeth Medical Center South

Edgewood, Kentucky, 41017, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Metro Minnesota Community Oncology Research Consortium

Saint Louis Park, Minnesota, 55416, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

New Hampshire Oncology Hematology PA-Hooksett

Hooksett, New Hampshire, 03106, United States

Location

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

Solinsky Center for Cancer Care

Manchester, New Hampshire, 03103, United States

Location

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

FirstHealth of the Carolinas-Moore Regional Hospital

Pinehurst, North Carolina, 28374, United States

Location

Altru Cancer Center

Grand Forks, North Dakota, 58201, United States

Location

University of Washington Medical Center - Montlake

Seattle, Washington, 98195, United States

Location

Mayo Clinic Health System-Eau Claire Clinic

Eau Claire, Wisconsin, 54701, United States

Location

Dean Hematology and Oncology Clinic

Madison, Wisconsin, 53717, United States

Location

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, 54449, United States

Location

Froedtert and the Medical College of Wisconsin LAPS

Milwaukee, Wisconsin, 53226, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (2)

• 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.

  PMID: 38537780 DERIVED

• 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.

  PMID: 31606897 DERIVED

MeSH Terms

Conditions

Intracranial Thrombosis; Venous Thrombosis; Hematologic Neoplasms; Neoplasm Metastasis; Pulmonary Embolism

Interventions

apixaban

Condition Hierarchy (Ancestors)

Intracranial Embolism and Thrombosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Thromboembolism; Embolism and Thrombosis; Thrombosis; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Embolism

Results Point of Contact

• Title: Dr. Robert McBane
• Organization: Mayo Clinic

mcbane.robert@mayo.edu

(507)266-3964

Study Officials

• Robert D McBane

  Academic and Community Cancer Research United

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2017
• First Posted: March 15, 2017
• Study Start: July 14, 2017
• Primary Completion: June 7, 2022
• Study Completion: May 9, 2025
• Last Updated: May 18, 2025
• Results First Posted: December 12, 2023

Record last verified: 2025-05

Locations

US (32)