Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 18 and over NCI NU-NCI-00B9 NCT00086723

Special Category: SPORE trial

Objectives

Primary

1. Determine the maximum tolerated dose and toxicity of captopril and tissue plasminogen activator (tPA) in patients with progressive metastatic cancer.
2. Determine the in vivo generation of angiostatin by western analysis in patients treated with this regimen.

Secondary

1. Determine the antitumor effect of this regimen in these patients.

Entry 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

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

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 3 months

Hematopoietic

• Granulocyte count at least 1,500/mm³
• Platelet count at least 100,000/mm³
• 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

Expected Enrollment

Not specified.

Outcomes

Angiostatin production

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.

Trial Contact Information

Trial Lead Organizations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

William Gradishar, MD, Principal investigator		Ph: 312-695-4125 Email: w-gradishar@northwestern.edu

Registry Information
Official Title		Phase I/II Trial of In Vivo Angiostatin Generation with Tissue Plasminogen Activator (tPA) and Captopril in Patients with Progressive, Metastatic Cancer
Trial Start Date		2003-07-11
Registered in ClinicalTrials.gov		NCT00086723
Date Submitted to PDQ		2003-11-14
Information Last Verified		2005-08-08
NCI Grant/Contract Number		P50-CA89018, P30-CA60553

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