Heart and Blood Diseases

All Conditions

Neoplasms

Symptoms and General Pathology

Respiratory Tract (Lung and Bronchial) Diseases

Thrombosis

Venous Thrombosis

Neoplasm Metastasis

Pulmonary Embolism

Embolism

Embolism and Thrombosis

Vascular Diseases

Lung Diseases

Respiratory Tract Diseases

Anticoagulants

All Drugs and Chemicals

Anti-Infective Agents

Amino Acids

Apixaban

Factor Xa Inhibitors

Antithrombins

Antithrombin III

Protease Inhibitors

Serine Proteinase Inhibitors

HIV Protease Inhibitors

Enzyme Inhibitors

Serine

Patients receive lower dose apixaban PO BID for 365 days.

Patients receive higher dose apixaban PO BID for 365 days.

Robert D McBane

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.

PRIMARY OBJECTIVE:

I. Any episode of major bleeding including fatal bleeding or clinically relevant non-major bleeding.

SECONDARY OBJECTIVES:

I. The proportion of patients who experienced at least one such bleeding event within 6 months of beginning treatment.

II. Venous thromboembolism (VTE) recurrence including deep vein thrombosis (DVT), pulmonary embolism (PE), fatal PE, or arterial thromboembolism.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive lower dose apixaban orally (PO) twice daily (BID) for 365 days.

GROUP II: Patients receive higher dose apixaban PO BID for 365 days.

After completion of study treatment, patients are followed up for 30 days.

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

A Phase III, Randomized, Controlled, Double-Blind Study Evaluating the Safety of Two Doses of Apixaban for Secondary Prevention of Cancer Related Venous Thrombosis in Subjects Who Have Completed at Least Six Months of Anticoagulation Therapy

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

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 6 months between treatment arms will be estimated along with a 95% confidence interval.

For the secondary outcome analysis, the time from starting treatment to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) outcome will be analyzed using the same method described in the section for primary outcome plan. For this outcome, death without DVT/PE and adverse events leading to termination of treatment will be treated as the competing risks.

National Cancer Institute (NCI)

Academic and Community Cancer Research United

Group I (2.5mg Dose Apixaban)

Group II (5mg Dose Apixaban)

Patients receive lower dose apixaban PO BID for 365 days.\>

\> Apixaban: Given PO

Patients receive higher dose apixaban PO BID for 365 days.\>

\> Apixaban: Given PO

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Primary Tumor Site

0 Fully active, able to carry on all pre-disease performance without restriction

1. Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work
2. Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours
3. Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours
4. Completely disabled; cannot carry on any selfcare; totally confined to bed or chair
5. Dead

ECOG Performance Status

Location of Initial Thrombosis

Dr. Robert McBane

Patients receive lower dose apixaban PO BID for 365 days. \>

\> Apixaban: Given PO

Patients receive higher dose apixaban PO BID for 365 days. \>

\> Apixaban: Given PO

CIF of Major or Clinically Relevant Non-major Bleeding Combined With Death as Competing Risk

Proportion of Patients Who Experienced at Least One Bleeding Event

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

Overall Study

Thromboembolism

Venous Thromboembolism

Fibrinolytic Agents

Heparin, Low-Molecular-Weight

Tinzaparin

Dalteparin

Heparin

Calcium heparin

Patients receive apixaban 10 mg PO BID on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.

Patients receive dalteparin 200 IU/kg/day SC QD on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.

Questionnaire Administration

Robert McBane

This randomized phase III trial studies the side effects of and compares apixaban and dalteparin in reducing blood clots in patients with cancer-related venous thromboembolism. Venous thromboembolism is a condition in which a blood clot forms in a vein and then breaks off and moves through the bloodstream. Patients with cancer are at increased risk for venous thromboembolism. Apixaban and dalteparin are drugs used to prevent blood clots from forming or to treat blood clots that have formed. It is not yet known whether apixaban or dalteparin is more effective in reducing blood clots in patients with cancer related venous thromboembolism.

ADAM-VTE

PRIMARY OBJECTIVES:

I. Any episode of major bleeding including fatal bleeding.

SECONDARY OBJECTIVES:

I. Venous thromboembolism (VTE) recurrence including deep vein thrombosis (DVT), pulmonary embolism (PE), fatal PE, or arterial thromboembolism.

II. Any episode of major bleeding including fatal bleeding or any episode of clinically relevant non-major bleeding.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive apixaban 10 mg orally (PO) twice daily (BID) on days 1-7 and lower-dose apixaban 5 mg PO BID on days 8-180.

ARM II: Patients receive dalteparin 200 international units (IU)/kg/day subcutaneously (SC) once daily (QD) on days 1-30 and lower-dose dalteparin 150 IU/kg/day SC QD on days 31-180.

After completion of study treatment, patients are followed up at 3 months.

Apixaban or Dalteparin in Reducing Blood Clots in Patients With Cancer Related Venous Thromboembolism

A Phase III, Randomized, Open Label Study Evaluating the Safety of Apixaban in Subjects With Cancer Related Venous Thromboembolism

The rate (percentage) of patients experiencing major bleeding at 6 months from treatment initiation and its associated 95% confidence interval was estimated separately by treatment arm using a cumulative incidence function, treating death without bleeding as a competing risk.

A similar analysis as described for the primary safety analysis will be used. The rate (percentage) of patients experiencing major bleeding or a clinically relevant non-major bleed at 6 months from treatment initiation and its associated 95% confidence interval was estimated separately by treatment arm using a cumulative incidence function, treating death without bleeding as a competing risk.

Analyzed using the same methods described above for the primary endpoint.Time to the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE) is defined as the time from randomization to the date the patient experienced the first event of the composite deep vein thrombosis (DVT)/pulmonary embolism (PE).

Adverse events are summarized below for patients who received at least one cycle of treatment (i.e. patients who completed the study and patients with unknown reason for not completing the study in the Participant Flow) and completed at least one adverse event form.

Arm A (Apixaban)

Arm B (Dalteparin)

Eastern Cooperative Oncology Group PS Scale: 0)Fully active, able to carry on all pre-disease performance without restriction; 1)Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; 2)Ambulatory and capable of all selfcare but unable to carry out any work activities. Up and about more than 50% of waking hours; 3)Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; 4)Completely disabled. Cannot carry on any selfcare. Totally confined to bed or chair.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Apixaban in Preventing Secondary Cancer Related Venous Thrombosis in Cancer Patients Who Have Completed Anticoagulation Therapy	NCT03080883	Cerebral Vein T... Deep Vein Throm... Hematopoietic a... Malignant Solid... Metastatic Mali... Pulmonary Embol... Splanchnic Vein...	Apixaban	18 Years -	Academic and Community Cancer Research United
Apixaban in Preventing Secondary Cancer Related Venous Thrombosis in Cancer Patients Who Have Completed Anticoagulation Therapy	NCT03080883	Cerebral Vein T... Deep Vein Throm... Hematopoietic a... Malignant Solid... Metastatic Mali... Pulmonary Embol... Splanchnic Vein...	Apixaban	18 Years -	Academic and Community Cancer Research United
Apixaban or Dalteparin in Reducing Blood Clots in Patients With Cancer Related Venous Thromboembolism	NCT02585713	Cerebral Vein T... Deep Vein Throm... Gonadal Thrombo... Hepatic Thrombo... Malignant Neopl... Mesenteric Thro... Metastatic Mali... Portal Vein Thr... Pulmonary Embol... Renal Vein Thro... Splenic Thrombo... Venous Thromboe...	Apixaban Dalteparin Questionnaire A...	18 Years -	Academic and Community Cancer Research United
Apixaban or Dalteparin in Reducing Blood Clots in Patients With Cancer Related Venous Thromboembolism	NCT02585713	Cerebral Vein T... Deep Vein Throm... Gonadal Thrombo... Hepatic Thrombo... Malignant Neopl... Mesenteric Thro... Metastatic Mali... Portal Vein Thr... Pulmonary Embol... Renal Vein Thro... Splenic Thrombo... Venous Thromboe...	Apixaban Dalteparin Questionnaire A...	18 Years -	Academic and Community Cancer Research United

Spots Global Cancer Trial Database for cerebral vein thrombosis