Angiotensin-(1-7) in Treating Patients With Metastatic or Unresectable Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: Angiotensin-(1-7) may stop the growth of solid tumors by blocking blood flow to the tumor. PURPOSE: This phase I trial is studying the side effects and best dose of angiotensin-(1-7) in treating patients with metastatic or unresectable solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of therapeutic angiotensin-(1-7) in patients with metastatic or unresectable solid tumors. Determine the pharmacokinetics of this drug in these patients. Secondary Determine tumor response in patients treated with this drug. OUTLINE: This is a dose-escalation study. Patients receive therapeutic angiotensin-(1-7) subcutaneously on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of therapeutic angiotensin-(1-7) 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 during the first 3 weeks of study therapy. At least 6 patients are treated at the MTD. Blood samples are collected from patients after the first and fifth doses of the study drug for pharmacokinetic correlative studies. PROJECTED ACCRUAL: A total of 18 patients will be accrued for this study.

Official Title
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Phase I Clinical Trial of Angiotensin 1-7 for Advanced Solid Tumors

Conditions
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Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Biological: therapeutic angiotensin-(1-7)


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed advanced solid tumor meeting 1 of the following criteria: Metastatic disease Unresectable disease Standard curative or palliative measures do not exist or are no longer effective Measurable or nonmeasurable disease Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan Nonmeasurable disease, defined as all other lesions, including small lesions (i.e., ≥ 1 unidimensionally measurable lesion < 20 mm by conventional techniques or < 10 mm by spiral CT scan) and truly nonmeasurable lesions, including any of the following: Bone lesions Ascites Pleural or pericardial effusion Lymphangitis cutis or pulmonis Abdominal masses not confirmed and followed by imaging techniques Cystic lesions No lung cancer with recent hemoptysis No brain metastasis PATIENT CHARACTERISTICS: ECOG performance status 0-2 Life expectancy > 4 weeks No evidence of bleeding diathesis Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception Granulocyte count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Creatinine clearance > 30 mL/min Bilirubin < 2 mg/dL AST and ALT < 3 times upper limit of normal No concurrent uncontrolled illness including, but not limited to, any of the following: Ongoing or active infection Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Uncontrolled hypertension or hypotension No psychiatric illness or social situation that would preclude informed consent or study compliance PRIOR CONCURRENT THERAPY: At least 4 weeks since prior major surgery At least 4 weeks since prior radiotherapy or chemotherapy (6 weeks for melphalan, nitrosoureas, or mitomycin C) No concurrent therapeutic anticoagulation No other concurrent investigational agents No concurrent angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers No concurrent combination antiretroviral therapy for HIV-positive patients

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: therapeutic angiotensin-(1-7)|sequentially increasing doses 50-1000 mcg/kg|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose |  | 21 days | 
| Toxicity |  | 105 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete or partial response) as measured by RECIST criteria |  | 105 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unspecified adult solid tumor, protocol specific