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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.
 
ClinicalTrials.gov Identifier: NCT00086723
Recruitment Status : Completed
First Posted : July 12, 2004
Last Update Posted : June 11, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Northwestern University

Tracking Information
First Submitted Date  ICMJE July 8, 2004
First Posted Date  ICMJE July 12, 2004
Last Update Posted Date June 11, 2012
Study Start Date  ICMJE July 2003
Actual Primary Completion Date January 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June¬†4,¬†2007)
Angiostatin production
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE In Vivo Angiostatin Generation Using Tissue Plasminogen Activator and Captopril in Treating Patients With Progressive Metastatic Cancer
Official Title  ICMJE Phase I/II Trial of In Vivo Angiostatin Generation With Tissue Plasminogen Activator (tPA) and Captopril in Patients With Progressive, Metastatic Cancer
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.

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE Unspecified Adult Solid Tumor, Protocol Specific
Intervention  ICMJE
  • Biological: recombinant tissue plasminogen activator
  • Drug: captopril
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE Not Provided
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE January 2006
Actual Primary Completion Date January 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00086723
Other Study ID Numbers  ICMJE NCI 00B9
NU-NCI-00B9
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: William J. Gradishar, MD Robert H. Lurie Cancer Center
PRS Account Northwestern University
Verification Date June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP