Phase I/II Trial of In Vivo Angiostatin Generation With Tissue Plasminogen Activator (tPA) and Captopril in Patients With Progressive, Metastatic Cancer

Date de début de l'étude : 1 juillet 2003

DISEASE CHARACTERISTICS: * Diagnosis of progressive metastatic cancer, excluding hematologic malignancies (i.e., leukemia or lymphoma) * Measurable disease not required * Must have received at least 1 prior systemic treatment for metastatic disease * No known CNS involvement * CNS involvement allowed provided it is successfully controlled by prior surgery or radiotherapy and there is no current requirement for corticosteroids PATIENT CHARACTERISTICS: Age * 18 and over Performance status * ECOG 0-2 Life expectancy * At least 3 months Hematopoietic * Granulocyte count at least 1,500/mm\^3 * Platelet count at least 100,000/mm\^3 * No bleeding diathesis Hepatic * Bilirubin no greater than 1.5 mg/dL * SGOT no greater than 3 times upper limit of normal * Albumin normal * PT and aPTT normal * Fibrinogen \> lower limit of normal Renal * Creatinine no greater than 1.8 mg/dL Cardiovascular * No myocardial infarction within the past 6 months * No history of stroke, transient ischemic attack, or symptoms of cerebral ischemia * No history of angioedema with captopril * No severe or uncontrolled hypertension (i.e., systolic blood pressure greater than 180 mm Hg or diastolic blood pressure greater than 110 mm Hg) * No congestive heart failure requiring therapy * No chronic hypotension (e.g., systolic blood pressure less than 100 mm Hg) Other * Not pregnant or nursing * Fertile patients must use effective contraception * HIV negative * Potassium no greater than 5.2 mmol/L * No active internal bleeding * No history of seizures * No psychiatric disorder that would preclude the giving of informed consent or study follow-up * No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No uncontrolled or active bacterial, viral, or invasive fungal infection * No recent trauma * No medical indication for anticoagulation * No contraindication to captopril PRIOR CONCURRENT THERAPY: Biologic therapy * At least 4 weeks since prior biologic therapy * No concurrent immunomodulator therapy Chemotherapy * At least 4 weeks since prior chemotherapy * No concurrent chemotherapy Endocrine therapy * See Disease Characteristics * At least 4 weeks since prior endocrine therapy Radiotherapy * See Disease Characteristics * At least 4 weeks since prior radiotherapy Surgery * See Disease Characteristics * No recent intracranial or intraspinal surgery * No concurrent surgery Other * More than 48 hours since prior anticoagulation agents (e.g., warfarin or heparin) * More than 3 weeks since prior investigational agents * No concurrent anticoagulation agents, aspirin, or nonsteroidal anti-inflammatory drugs * No other concurrent investigational agent * No concurrent phenytoin, phenobarbital, or other antiepileptic prophylaxis * Concurrent bisphosphonates allowed for metastatic bone disease