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

• Status: Completed
• Trial end date: 2006-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Northwestern University
• Collaborator: National Cancer Institute (NCI)
• Treatments: Angiostatins; Captopril; Plasminogen; Tissue Plasminogen Activator

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