In Vivo Angiostatin Generation Using Tissue Plasminogen Activator and Captopril in Treating Patients With Progressive Metastatic Cancer
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.
Description
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.
Study Design
Primary Purpose: Treatment
Conditions
Unspecified Adult Solid Tumor, Protocol Specific
Intervention
recombinant tissue plasminogen activator, captopril
Location
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago
Illinois
United States
60611-3013
Status
Active, not recruiting
Source
National Cancer Institute (NCI)
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00086723
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Anistreplase
An acylated inactive complex of streptokinase and human lysine-plasminogen. After injection, the acyl group is slowly hydrolyzed, producing an activator that converts plasminogen to plasmin, thereby initiating fibrinolysis. Its half-life is about 90 minutes compared to 5 minutes for TPA; (TISSUE PLASMINOGEN ACTIVATOR); 16 minutes for UROKINASE-TYPE PLASMINOGEN ACTIVATOR and 23 minutes for STREPTOKINASE. If treatment is initiated within 3 hours of onset of symptoms for acute myocardial infarction, the drug preserves myocardial tissue and left ventricular function and increases coronary artery patency. Bleeding complications are similar to other thrombolytic agents.
Tissue Plasminogen Activator
A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.
Receptors, Urokinase Plasminogen Activator
An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.
Plasminogen Activator Inhibitor 1
A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.
Plasminogen Activator Inhibitor 2
Member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.
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