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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Northwestern University
ClinicalTrials.gov Identifier:
NCT00086723
First received: July 8, 2004
Last updated: June 7, 2012
Last verified: June 2012
  Purpose

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 Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Biological: recombinant tissue plasminogen activator
Drug: captopril
Phase 1
Phase 2

Study Type: Interventional
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • Angiostatin production [ Designated as safety issue: No ]

Study Start Date: July 2003
Study Completion Date: January 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00086723

Locations
United States, Illinois
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: William J. Gradishar, MD Robert H. Lurie Cancer Center
  More Information

No publications provided

Responsible Party: Northwestern University
ClinicalTrials.gov Identifier: NCT00086723     History of Changes
Other Study ID Numbers: NCI 00B9, NU-NCI-00B9
Study First Received: July 8, 2004
Last Updated: June 7, 2012
Health Authority: United States: Federal Government

Keywords provided by Northwestern University:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplastic Processes
Pathologic Processes
Angiostatins
Captopril
Plasminogen
Tissue Plasminogen Activator
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Angiotensin-Converting Enzyme Inhibitors
Antihypertensive Agents
Antineoplastic Agents
Cardiovascular Agents
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Growth Inhibitors
Growth Substances
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014