in vivo angiostatin generation using tissue plasminogen activator and captopril in treating patients with progressive metastatic cancer

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: rationale: tissue plasminogen activator and captopril may help the body generate angiostatin. angiostatin may stop the growth of cancer by stopping blood flow to the tumor. purpose: this phase i/ii trial is studying the side effects and best dose of tissue plasminogen activator and captopril and to see how well they work in treating patients with progressive metastatic cancer.

objectives: primary * determine the maximum tolerated dose and toxicity of captopril and tissue plasminogen activator (tpa) in patients with progressive metastatic cancer. * determine the in vivo generation of angiostatin by western analysis in patients treated with this regimen. secondary * determine the antitumor effect of this regimen in these patients. outline: this is a dose-escalation study. patients receive tissue plasminogen activator (tpa) iv over 6 hours and oral captopril twice daily on days 1-5. courses repeat every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity. patients who achieve a complete response (cr) receive 2 additional courses beyond cr. cohorts of 3-6 patients receive escalating doses of tpa and captopril until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. projected accrual: not specified.

Eligibility criteria:
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

Keywords: unspecified adult solid tumor, protocol specific