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

Phase 2

Completed

Conditions: Pulmonary Embolism
Cancer
Thrombosis

Interventions: Drug: Placebo
Drug: Apixaban

Registration Number: NCT00320255

Lead Sponsor: Bristol-Myers Squibb

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 130

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: Placebo	Placebo	Participants received placebo tablets once daily
Cohort 2: Placebo	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.
Cohort 1: Apixaban, 5 mg	Apixaban	Participants received apixaban as tablet, 5 mg, once daily
Cohort 1: Apixaban, 10 mg	Apixaban	Participants received apixaban as tablet, 10 mg, once daily
Cohort 1: Apixaban, 20 mg	Apixaban	Participants received apixaban as tablet, 20 mg, once daily
Cohort 2: Apixaban, 5 mg	Apixaban	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Composite of Confirmed Major Bleeding and Clinically Relevant Nonmajor (CRNM) Bleeding	From first dose to 2 days following last dose of study drug	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

Name	Time	Method
Number of Participants With Nonfatal Pulmonary Embolism	First dose to 2 days following last dose of study drug	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 Distal Deep Vein Thrombosis	First dose to 2 days following last dose of study drug	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 Composite of Venous Thromboembolism (VTE) and All-cause Death	First dose to 2 days following last dose of study drug	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 Pulmonary Embolism (Fatal or Nonfatal)	First dose to 2 days following last dose of study drug	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 Composite of Venous Thromboembolism (VTE) and VTE-related Death	First dose to 2 days following last dose of study drug	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 All-Cause Death	First dose to 2 days following last dose of study drug
Number of Participants With Deep Vein Thrombosis	First dose to 2 days following last dose of study drug	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 (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death	First dose to 30 days following last dose of study drug	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 Proximal Deep Vein Thrombosis	First dose to 2 days following last dose of study drug	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	First dose to 2 days following last dose of study drug	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.
Number of Participants With Composite of Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and Venous Thromboembolism (VTE)-Related Death	First dose to 2 days following last dose of study drug	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.

Trial Locations

Locations (9): Arizona Cancer Center
🇺🇸
Tucson, Arizona, United States
Univ. Of Southern Calif. /Norris Comprehensive Cancer Center
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Los Angeles, California, United States
Mount Sinai School Of Medicine
🇺🇸
New York, New York, United States
Dana-Farber Cancer Inst
🇺🇸
Boston, Massachusetts, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Nevada Cancer Institute
🇺🇸
Las Vegas, Nevada, United States
University Of Rochester
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Rochester, New York, United States
University Of Texas Md Anderson Cancer Ctr
🇺🇸
Houston, Texas, United States
Local Institution
🇨🇦
Montreal, Quebec, Canada