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

June 7, 2012 updated by: Northwestern University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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 Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611-3013
        • Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Angiostatin production

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: William J. Gradishar, MD, Robert H. Lurie Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2003

Primary Completion (Actual)

January 1, 2006

Study Completion (Actual)

January 1, 2006

Study Registration Dates

First Submitted

July 8, 2004

First Submitted That Met QC Criteria

July 9, 2004

First Posted (Estimate)

July 12, 2004

Study Record Updates

Last Update Posted (Estimate)

June 11, 2012

Last Update Submitted That Met QC Criteria

June 7, 2012

Last Verified

June 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI 00B9
  • NU-NCI-00B9

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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