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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00086723
Recruitment Status : Completed
First Posted : July 12, 2004
Last Update Posted : June 11, 2012
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Brief 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.

Condition or disease Intervention/treatment Phase
Unspecified Adult Solid Tumor, Protocol Specific Biological: recombinant tissue plasminogen activator Drug: captopril Phase 1 Phase 2

Detailed Description:



  • 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.


  • 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.


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Study Type : Interventional  (Clinical Trial)
Primary Purpose: Treatment
Official Title: Phase I/II Trial of In Vivo Angiostatin Generation With Tissue Plasminogen Activator (tPA) and Captopril in Patients With Progressive, Metastatic Cancer
Study Start Date : July 2003
Actual Primary Completion Date : January 2006
Actual Study Completion Date : January 2006

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. Angiostatin production

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 3 months


  • Granulocyte count at least 1,500/mm^3
  • Platelet count at least 100,000/mm^3
  • No bleeding diathesis


  • 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


  • Creatinine no greater than 1.8 mg/dL


  • 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)


  • 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


Biologic therapy

  • At least 4 weeks since prior biologic therapy
  • No concurrent immunomodulator therapy


  • At least 4 weeks since prior chemotherapy
  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 4 weeks since prior endocrine therapy


  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy


  • See Disease Characteristics
  • No recent intracranial or intraspinal surgery
  • No concurrent surgery


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00086723

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United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
National Cancer Institute (NCI)
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Principal Investigator: William J. Gradishar, MD Robert H. Lurie Cancer Center
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Responsible Party: Northwestern University Identifier: NCT00086723    
Other Study ID Numbers: NCI 00B9
First Posted: July 12, 2004    Key Record Dates
Last Update Posted: June 11, 2012
Last Verified: June 2012
Keywords provided by Northwestern University:
unspecified adult solid tumor, protocol specific
Additional relevant MeSH terms:
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Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Angiotensin-Converting Enzyme Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Antihypertensive Agents