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Phase I/II Trial of In Vivo Angiostatin Generation With Tissue Plasminogen Activator (tPA) and Captopril in Patients With Progressive, Metastatic Cancer


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I/II Trial of In Vivo Angiostatin Generation With Tissue Plasminogen Activator (tPA) and Captopril in 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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Angiostatin production

Safety Issue:

No

Principal Investigator

William J. Gradishar, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Robert H. Lurie Cancer Center

Authority:

United States: Federal Government

Study ID:

NCI 00B9

NCT ID:

NCT00086723

Start Date:

July 2003

Completion Date:

January 2006

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • unspecified adult solid tumor, protocol specific
  • Neoplasm Metastasis

Name

Location

Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611