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.
- Determine the maximum tolerated dose and toxicity of captopril and tissue plasminogen
- Determine the in vivo generation of angiostatin by western analysis in patients treated
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.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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