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

Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00320255
• Other study ID #: CV185-027
• Status: Completed
• Phase: Phase 2
• First received: April 28, 2006
• Last updated: August 11, 2016
• Start date: June 2006
• Est. completion date: January 2009

Study information

• Verified date: August 2016
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 130
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 90 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cancer
• Embolism
• Pulmonary Embolism
• Thromboembolism
• Thrombosis

Intervention

Drug:
• Apixaban
Oral tablets administered once daily in 5-, 10-, or 20-mg dose
• Placebo
Oral tablets administered once daily

Locations

Country	Name	City	State
Canada	Local Institution	Hamilton	Ontario
Canada	Local Institution	London	Ontario
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Montreal	Quebec
Canada	Local Institution	Toronto	Ontario
Canada	Local Institution	Toronto	Ontario
United States	Dana-Farber Cancer Inst	Boston	Massachusetts
United States	University Of Texas Md Anderson Cancer Ctr	Houston	Texas
United States	Nevada Cancer Institute	Las Vegas	Nevada
United States	Univ. Of Southern Calif. /Norris Comprehensive Cancer Center	Los Angeles	California
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	Arizona Cancer Center	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ontario Clinical Oncology Group (OCOG)

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From first dose to 2 days following last dose of study drug	Yes
Secondary	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.	First dose to 2 days following last dose of study drug	No
Secondary	Number of Participants With Proximal Deep Vein Thrombosis (DVT), Nonfatal Pulmonary Embolism (PE), and All-cause Death	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.	First dose to 30 days following last dose of study drug	No
Secondary	Number of Participants With Composite of Venous Thromboembolism (VTE) and VTE-related 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.	First dose to 2 days following last dose of study drug	No
Secondary	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.	First dose to 2 days following last dose of study drug	No
Secondary	Number of Participants With All-Cause Death		First dose to 2 days following last dose of study drug	No
Secondary	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.	First dose to 2 days following last dose of study drug	No
Secondary	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.	First dose to 2 days following last dose of study drug	No
Secondary	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.	First dose to 2 days following last dose of study drug	No
Secondary	Number of Participants With Distal 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.	First dose to 2 days following last dose of study drug	No
Secondary	Number of Participants With Proximal 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.	First dose to 2 days following last dose of study drug	No
Secondary	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.	First dose to 2 days following last dose of study drug	Yes

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm
•   Investigator Inquiry form