In Vivo Angiostatin Generation Using Tissue Plasminogen Activator and Captopril in Treating 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.

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 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