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

Phase 2CompletedNCT00320255

Bristol-Myers Squibb130 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

DOUBLE

Enrollment

130

Conditions

Thrombosis Cancer Pulmonary Embolism

Interventions

ApixabanDRUG

Oral tablets administered once daily in 5-, 10-, or 20-mg dose

PlaceboDRUG

Oral tablets administered once daily

Eligibility

Sex: ALLMin age: 18 YearsMax age: 90 Years

Medical Language ↔ Plain English

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.

Locations (14)

Arizona Cancer Center

Tucson, Arizona, United States

Univ. Of Southern Calif. /Norris Comprehensive Cancer Center

Los Angeles, California, United States

Dana-Farber Cancer Inst

Boston, Massachusetts, United States

Outcomes

Primary Outcomes

Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding

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.

Time frame: From first dose to 2 days following last dose of study drug

Secondary Outcomes

Number of Participants With Composite of Venous Thromboembolism (VTE) and All-cause Death

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.

Time frame: First dose to 2 days following last dose of study drug

Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death

Data from ClinicalTrials.gov

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Nevada Cancer Institute

Las Vegas, Nevada, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Mount Sinai School Of Medicine

New York, New York, United States

University Of Rochester

Rochester, New York, United States

University Of Texas Md Anderson Cancer Ctr

Houston, Texas, United States

Local Institution

Hamilton, Ontario, Canada

Local Institution

London, Ontario, Canada

...and 4 more locations

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.

Time frame: First dose to 30 days following last dose of study drug

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

Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death

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.

Time frame: First dose to 2 days following last dose of study drug

Number of Participants With All-Cause Death

Time frame: First dose to 2 days following last dose of study drug

Number of Participants With Pulmonary Embolism (Fatal or Nonfatal)

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.

Time frame: First dose to 2 days following last dose of study drug

Number of Participants With Nonfatal Pulmonary Embolism

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.

Time frame: First dose to 2 days following last dose of study drug

Number of Participants With Deep Vein Thrombosis

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.

Time frame: First dose to 2 days following last dose of study drug

Number of Participants With Distal Deep Vein Thrombosis

Time frame: First dose to 2 days following last dose of study drug

Number of Participants With Proximal Deep Vein Thrombosis

Time frame: First dose to 2 days following last dose of study drug

Number of Participants Who Died and With Adverse Events (AEs), Serious Adverse Events (SAEs), Bleeding AEs, and Discontinuations Due to AEs

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.

Time frame: First dose to 2 days following last dose of study drug