In Vivo Angiostatin Generation Using Tissue Plasminogen Activator and Captopril in Treating Patients With Progressive Metastatic Cancer
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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 |
- 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) |
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 |
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| United States, Illinois | |
| Robert H. Lurie Comprehensive Cancer Center at Northwestern University | |
| Chicago, Illinois, United States, 60611-3013 | |
| 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 Neoplastic Processes Neoplasms Pathologic Processes Captopril Plasminogen Tissue Plasminogen Activator Angiostatins Angiotensin-Converting Enzyme Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions |
Antihypertensive Agents Cardiovascular Agents Therapeutic Uses Fibrinolytic Agents Fibrin Modulating Agents Hematologic Agents Angiogenesis Inhibitors Angiogenesis Modulating Agents Growth Substances Physiological Effects of Drugs Growth Inhibitors Antineoplastic Agents |
ClinicalTrials.gov processed this record on May 19, 2013