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.

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.

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