angiotensin-(1-7) in treating patients with metastatic or unresectable solid tumors

Conditions: Unspecified Adult Solid Tumor, Protocol Specific

Summary: 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.

Eligibility criteria:
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

Keywords: unspecified adult solid tumor, protocol specific