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A Phase 2 Pilot Study of Apixaban for the Prevention of Thromboembolic Events in Patients With Advanced (Metastatic) Cancer

This study has been completed.
Sponsor:
Collaborator:
Ontario Clinical Oncology Group (OCOG)
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00320255
First received: April 28, 2006
Last updated: August 11, 2016
Last verified: August 2016
  Purpose
The purpose of this study is to learn whether apixaban is well-tolerated and acceptable as anticoagulant therapy, when administered to patients with advanced or metastatic cancer and at increased risk for venous thromboembolic events. Demonstration of a favorable benefit:risk profile could lead to significant reduction in this serious and sometimes fatal complication of ongoing cancer and its treatment.

Condition Intervention Phase
Thrombosis
Cancer
Pulmonary Embolism
Drug: Apixaban
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blind, Placebo-controlled Study of Apixaban for the Prevention of Thromboembolic Events in Patients Undergoing Treatment for Advanced Cancer: A Phase 2 Pilot Study

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding [ Time Frame: From first dose to 2 days following last dose of study drug ] [ Designated as safety issue: Yes ]

    Major bleeding was defined as clinically overt bleeding accompanied by 1 or more of the following:

    • A decrease in hemoglobin of 20 g/L or more or
    • Required transfusion of 2 or more units of packed red blood cells or whole blood, or
    • Occurred in a critical site
    • Contributed to death.

    CRNM bleeding was defined as bleeding that did not meet the criteria for major bleeding but that, in routine clinical practice, would be considered relevant and not trivial by a patient and physician. Such bleeding satisfied a priori criteria defined by the ICAC, including:

    • Skin hematoma
    • Epistaxis that lasted for longer than 5 minutes, was repetitive, or led to an intervention
    • Hematuria that was macroscopic and either spontaneous or lasted for longer than 24 hours after instrumentation of the urogenital tract
    • Any other bleeding type that was considered to have clinical consequences.


Secondary Outcome Measures:
  • Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT:

    • New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS
    • Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

    Any 1 of the following was considered diagnostic for PE:

    • Constant intraluminal filling defects in 2 or more views on pulmonary angiography
    • Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram
    • A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect)
    • An abnormal VQ lung scan with satisfaction of either criterion 1 or 2
    • Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

  • Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death [ Time Frame: First dose to 30 days following last dose of study drug ] [ Designated as safety issue: No ]

    Any 1 of the following was considered diagnostic for DVT:

    • New or previously undocumented noncompressibility of 1 or more proximal venous segments (popliteal vein or higher) of the legs on CUS
    • Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

    Any 1 of the following was considered diagnostic for PE:

    • Constant intraluminal filling defects in 2 or more views on pulmonary angiography
    • Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram
    • A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect)
    • An abnormal VQ lung scan (nonhigh probability) with satisfaction of either criterion 1 or 2
    • Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

  • Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related Death [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    VTE includes symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE). Any 1 of the following was considered diagnostic for DVT:

    • New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS
    • Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

    Any 1 of the following was considered diagnostic for PE:

    • Constant intraluminal filling defects in 2 or more views on pulmonary angiography
    • Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram
    • A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect)
    • An abnormal VQ lung scan with satisfaction of either criterion 1 or 2
    • Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

  • Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    VTE includes symptomatic DVT and PE. Any 1 of the following was considered diagnostic for DVT:

    • New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS
    • Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

    Any 1 of the following was considered diagnostic for PE:

    • Constant intraluminal filling defects in 2 or more views on pulmonary angiography
    • Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram
    • A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect)
    • An abnormal VQ lung scan with satisfaction of either criterion 1 or 2
    • Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

  • Number of Participants With All-Cause Death [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]
  • Number of Participants With Pulmonary Embolism (Fatal or Nonfatal) [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    Any 1 of the following was considered diagnostic for PE:

    • Constant intraluminal filling defects in 2 or more views on pulmonary angiography
    • Sudden contrast cutoff of 1 or more vessels of greater than 2.5 mm in diameter on a pulmonary angiogram
    • A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect)
    • An abnormal VQ lung scan with satisfaction of either criterion 1 or 2
    • Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

  • Number of Participants With Nonfatal Pulmonary Embolism [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    Any 1 of the following was considered diagnostic for PE:

    • Constant intraluminal filling defects in 2 or more views on pulmonary angiography
    • Sudden contrast cutoff of 1 or more vessels more than 2.5 mm in diameter on a pulmonary angiogram
    • A high probability VQ lung scan showing 1 or more segmental perfusion defects with corresponding normal ventilation (mismatch defect)
    • An abnormal VQ lung scan with satisfaction of either criterion 1 or 2
    • Abnormal spiral computed tomography scan showing thrombus in pulmonary vessels.

  • Number of Participants With Deep Vein Thrombosis [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    Any 1 of the following was considered diagnostic for DVT:

    • New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS
    • Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

  • Number of Participants With Distal Deep Vein Thrombosis [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    Any 1 of the following was considered diagnostic for DVT:

    • New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS
    • Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

  • Number of Participants With Proximal Deep Vein Thrombosis [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: No ]

    Any 1 of the following was considered diagnostic for DVT:

    • New or previously undocumented noncompressibility of 1 or more proximal venous segments of the legs on CUS
    • Constant intraluminal filling defects on 2 or more views on contrast venography in 1 or more venous segments in the legs or pelvis or involving the inferior vena cava.

  • Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs [ Time Frame: First dose to 2 days following last dose of study drug ] [ Designated as safety issue: Yes ]
    AE=any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency/abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization.


Enrollment: 130
Study Start Date: June 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Cohort 1: Placebo
Participants received placebo tablets once daily
Drug: Placebo
Oral tablets administered once daily
Placebo Comparator: Cohort 1: Apixaban, 5 mg
Participants received apixaban as tablet, 5 mg, once daily
Drug: Apixaban
Oral tablets administered once daily in 5-, 10-, or 20-mg dose
Other Name: BMS-562247
Active Comparator: Cohort 1: Apixaban, 10 mg
Participants received apixaban as tablet, 10 mg, once daily
Drug: Apixaban
Oral tablets administered once daily in 5-, 10-, or 20-mg dose
Other Name: BMS-562247
Active Comparator: Cohort 1: Apixaban, 20 mg
Participants received apixaban as tablet, 20 mg, once daily
Drug: Apixaban
Oral tablets administered once daily in 5-, 10-, or 20-mg dose
Other Name: BMS-562247
Placebo Comparator: Cohort 2: Placebo
Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received placebo once daily.
Drug: Placebo
Oral tablets administered once daily
Active Comparator: Cohort 2: Apixaban, 5 mg
Participants in this cohort were admitted to the trial following the addition of a protocol amendment (Amendment 5), which removed the prohibition of inclusion of patients receiving chemotherapy with concomitant antiangiogenic therapy with bevacizumab. Patients received apixaban as tablet, 5 mg, once daily.
Drug: Apixaban
Oral tablets administered once daily in 5-, 10-, or 20-mg dose
Other Name: BMS-562247

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Recipients of either first- or second-line chemotherapy for advanced or metastatic lung, breast, gastrointestinal, bladder, ovarian, or prostate cancer or myeloma, selected lymphomas, or cancer of unknown origin
  • Able to begin study medication ≤6 weeks of starting either first- or second-line chemotherapy.
  • Expected course of chemotherapy must have been ≥ 90 days after the start of chemotherapy
  • Per Protocol Amendment 5, patients receiving bevacizumab were eligible to participate, provided that bevacizumab was used for indications approved by local country law

Key Exclusion Criteria:

  • Women who are pregnant, breastfeeding
  • History of deep vein thrombosis or pulmonary embolism
  • Active bleeding or at high risk of bleeding
  • Metastatic brain cancer
  • Familial bleeding diathesis
  • Serious hemorrhage requiring hospitalization, transfusion, or surgical intervention within 4 weeks of study entry
  • Expected survival <6 months or an Eastern Cooperative Oncology Group performance status ≥3.
  • Candidates for bone marrow transplantation within the 12-week treatment period or 30-day follow-up period
  • Uncontrolled hypertension (systolic blood pressure >200 mm Hg and/or diastolic blood pressure >110 mm Hg
  • Coagulopathy (international normalized ratio >1.5 or platelet count <100*10^9/L) if not yet receiving chemotherapy or <50*10^9/L if receiving chemotherapy). Platelet count must have been >100*10^9/L before starting study medication
  • One or more of the following: alanine aminotransferase >3 times the upper limit of normal (ULN), total bilirubin >2*ULN, or calculated creatinine clearance <30 mL/min.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00320255

Locations
United States, Arizona
Arizona Cancer Center
Tucson, Arizona, United States, 85724
United States, California
Univ. Of Southern Calif. /Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033
United States, Massachusetts
Dana-Farber Cancer Inst
Boston, Massachusetts, United States, 02115
United States, Nevada
Nevada Cancer Institute
Las Vegas, Nevada, United States, 89135
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Mount Sinai School Of Medicine
New York, New York, United States, 10029
University Of Rochester
Rochester, New York, United States, 14642
United States, Texas
University Of Texas Md Anderson Cancer Ctr
Houston, Texas, United States, 77030
Canada, Ontario
Local Institution
Hamilton, Ontario, Canada, L8V 2C5
Local Institution
London, Ontario, Canada, N6A 4L6
Local Institution
Toronto, Ontario, Canada, M4N 3M5
Local Institution
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Local Institution
Montreal, Quebec, Canada, H1T 2M4
Local Institution
Montreal, Quebec, Canada, H3G 1A4
Sponsors and Collaborators
Bristol-Myers Squibb
Ontario Clinical Oncology Group (OCOG)
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00320255     History of Changes
Other Study ID Numbers: CV185-027 
Study First Received: April 28, 2006
Results First Received: March 14, 2016
Last Updated: August 11, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Bristol-Myers Squibb:
anticoagulant

Additional relevant MeSH terms:
Apixaban
Thrombosis
Embolism
Pulmonary Embolism
Thromboembolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Factor Xa Inhibitors
Antithrombins
Serine Proteinase Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anticoagulants

ClinicalTrials.gov processed this record on December 09, 2016