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.

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.

1 year