In Vivo Angiostatin Generation Using Tissue Plasminogen Activator and Captopril in Treating Patients With Progressive Metastatic Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: recombinant tissue plasminogen activator
* Drug: captopril


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: recombinant tissue plasminogen activator|nan|
|Drug: captopril|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Angiostatin production |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific