Cancer Patients First-ever Acute Ischemic Stroke
Conditions
Keywords
Enoxaparin, Aspirin, stroke, 12-264
Brief summary
Patients with cancer who develop stroke are at high risk for future strokes or other clotting events. These patients are routinely treated with medicines that thin their blood, including enoxaparin or aspirin. However, it is unclear which medicine is best and whether these medicines can be adequately studied in a clinical trial. The purpose of this Phase I/II study is to determine if a clinical trial of different blood thinners in patients with cancer and stroke is possible. In addition, the study aims to compare the effects, good and/or bad, of enoxaparin with those of aspirin on patients with cancer and recent stroke.
Interventions
DRUGEnoxaparin
Patients will be receive 6 months of subcutaneous enoxaparin (1 mg/kg BID with a maximum starting dose of 100 mg BID. Patients who weigh more than 100 kg will start at a dose of 100 mg BID; their subsequent dosing will be guided by hematology and may change.
DRUGAspirin
Patients will receive 6 months of oral aspirin (81 mg per day unless a higher dose is preferred by study physicians although the maximum acceptable dose will be 325 mg per day).
Sponsors
New York Presbyterian Hospital
Weill Medical College of Cornell University
Memorial Sloan Kettering Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Any adult patient with active systemic cancer diagnosed with acute ischemic stroke at the main MSKCC campus or at any of MSKCC's New York City outpatient center WCMC, NYPH/CUMC within the prior four weeks would be eligible. Inclusion Criteria: * 18 to 85 years of age. * Active cancer, defined as a pathologic diagnosis of or treatment for any cancer, other than basal-cell or squamous-cell carcinoma of the skin, within the past six months; or patients with known recurrent or metastatic disease within the past six months. * A pathology report issued at the enrolling site confirming the diagnosis of cancer is required for enrollment. * Acute ischemic stroke within the prior four weeks, defined as a new neurologic deficit(s) with MRI evidence of acute ischemia in a referable location, and no clinical or radiologic indication of a non-cerebrovascular mimic, such as a brain metastasis, as the etiology of the deficit(s).
Exclusion criteria
* Inability to get brain MRI * Known malignant primary brain tumor. * Diagnosis of intracranial hemorrhage within the past 3 months, including intratumoral hemorrhage into brain metastases from a systemic cancer. * Active or serious bleeding within two weeks of enrollment. * Patient condition associated with a high risk of bleeding such as recent surgery or peptic ulcer disease. * Clear indication for anticoagulation (e.g., atrial fibrillation) anticipated during the study period. * Clear indication for antiplatelet agents (e.g., cardiac stents); a patient receiving aspirin for primary prevention prior to index stroke may be enrolled as long as study investigators believe it would be safe for the patient to stop aspirin if the patient was randomized to the enoxaparin arm. * Active bleeding diathesis. * Platelet count of ≤ 70,000/mm3, an international normalized ratio (INR) \> 1.6, or a partial thromboplastin time (PTT) \> 40 seconds. * Known allergy to heparin or aspirin or a history of heparin induced thrombocytopenia. * Serum creatinine \> 2 mg/dl. * AST or ALT \> 200 U/L. * Hemoglobin \< 8 gm/dl * Symptomatic carotid stenosis. * Active pregnancy. * Life expectancy \< 1 month or current hospice care * Unavailability for follow-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcomes | 1 year | Number of Participants with intracranial hemorrhage, symptomatic intracranial hemorrhage, major bleeding, and death |
| Feasibility Outcomes | 6 months | The primary feasibility outcome is patient enrollment defined as the number of patients who enroll in the study divided by the number of patients who were eligible to enroll. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With or Without Recurrent Ischemic Stroke | 6 months | Secondary efficacy outcomes will be assessed for and will include recurrent ischemic stroke, all strokes (ischemic or hemorrhagic), transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism, and systemic arterial thrombosis. Functional outcomes will also be evaluated, including the modified Rankin Scale score, the National Institute of Health Stroke Scale, and the Karnofsky Performance Status Scale. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Enoxaparin Patients assigned to enoxaparin.
Enoxaparin: Patients will be receive 6 months of subcutaneous enoxaparin (1 mg/kg BID with a maximum starting dose of 100 mg BID. Patients who weigh more than 100 kg will start at a dose of 100 mg BID; their subsequent dosing will be guided by hematology and may change. | 10 |
| Aspirin Patients assigned to Aspirin.
Aspirin: Patients will receive 6 months of oral aspirin (81 mg per day unless a higher dose is preferred by study physicians although the maximum acceptable dose will be 325 mg per day). | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | Enoxaparin | Total | Aspirin |
|---|---|---|---|
| Age, Continuous | 68 years | 71 years | 71 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 20 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 12 Participants | 8 Participants |
| Region of Enrollment United States | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 8 Participants | 15 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 5 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 10 | 6 / 10 |
| other Total, other adverse events | 10 / 10 | 10 / 10 |
| serious Total, serious adverse events | 5 / 10 | 6 / 10 |
Outcome results
Primary
Feasibility Outcomes
The primary feasibility outcome is patient enrollment defined as the number of patients who enroll in the study divided by the number of patients who were eligible to enroll.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Enoxaparin | Feasibility Outcomes | 41 percentage of eligible pts enrolled |
Primary
Safety Outcomes
Number of Participants with intracranial hemorrhage, symptomatic intracranial hemorrhage, major bleeding, and death
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enoxaparin | Safety Outcomes | Fatal Recurrent AIS | 1 Participants |
| Enoxaparin | Safety Outcomes | Nonfatal gastrointestinal bleeding | 0 Participants |
| Enoxaparin | Safety Outcomes | Nonfatal pulmonary hemorrhage | 1 Participants |
| Enoxaparin | Safety Outcomes | No hemorrahage, major bleeding or death | 8 Participants |
| Aspirin | Safety Outcomes | No hemorrahage, major bleeding or death | 7 Participants |
| Aspirin | Safety Outcomes | Fatal Recurrent AIS | 0 Participants |
| Aspirin | Safety Outcomes | Nonfatal pulmonary hemorrhage | 0 Participants |
| Aspirin | Safety Outcomes | Nonfatal gastrointestinal bleeding | 3 Participants |
Secondary
Number of Participants With or Without Recurrent Ischemic Stroke
Secondary efficacy outcomes will be assessed for and will include recurrent ischemic stroke, all strokes (ischemic or hemorrhagic), transient ischemic attack, myocardial infarction, deep vein thrombosis, pulmonary embolism, and systemic arterial thrombosis. Functional outcomes will also be evaluated, including the modified Rankin Scale score, the National Institute of Health Stroke Scale, and the Karnofsky Performance Status Scale.
Time frame: 6 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Enoxaparin | Number of Participants With or Without Recurrent Ischemic Stroke | Recurrent ischemic event | 1 Participants |
| Enoxaparin | Number of Participants With or Without Recurrent Ischemic Stroke | No recurrent ischemic event | 9 Participants |
| Aspirin | Number of Participants With or Without Recurrent Ischemic Stroke | Recurrent ischemic event | 0 Participants |
| Aspirin | Number of Participants With or Without Recurrent Ischemic Stroke | No recurrent ischemic event | 10 Participants |