Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery

PRIMARY OBJECTIVES:

I. To evaluate the response rate of chemotherapy-refractory sarcomas to 20 mg per day of
single-agent Ang(Angiotensin)-(1-7) or 10 mg per day of single-agent Ang-(1-7) if excessive
toxicity is observed at the 20 mg dose.

II. To evaluate toxicities associated with single-agent Ang-(1-7) when given to patients with
chemotherapy-refractory sarcomas.

SECONDARY OBJECTIVES:

I. To assess time to progression (TTP) and overall survival (OS) in patients treated with
Ang-(1-7).

II. To evaluate accumulation of Ang-(1-7) after 21 days of continuous treatment and quantify
changes in plasma levels of angiogenic peptides including placental growth factor (PlGF).

OUTLINE:

Patients receive therapeutic angiotensin-(1-7) subcutaneously (SC) once daily in the absence
of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3 months for 2 years, every
6 months for 3 years, and then annually thereafter.

Inclusion Criteria:

- Patients must have a histologically or cytologically confirmed sarcoma that is
metastatic or unresectable and have progressed despite 1 or 2 prior treatment regimens
with chemotherapy or targeted anti-cancer agents such as imatinib

- Prior treatment: >= 4 weeks since completion of radiation or chemotherapy, except for
>= 6 weeks for Melphalan, nitrosoureas, or mitomycin-C

- Eastern Cooperative Oncology Group (ECOG) performance status =< 2

- Absolute neutrophil count >= 1,500/Microliter (mcL)

- Platelets >= 100,000/mcL

- Total bilirubin =< 2 mg/dL

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) <
3 X upper limit or normal (ULN)

- Estimated (est.) creatinine clearance > 30 mL/min

- Measurable disease, defined as at least one lesion that can be accurately measured in
at least one dimension as > 10 mm

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or double-barrier method of birth control; abstinence) prior to study entry
and for the duration of study participation; should a woman become pregnant or suspect
she is pregnant while participating in this study, she should inform her treating
physician immediately

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- Patients may not be receiving any other investigational agents for cancer treatment

- Patients with evidence of bleeding diathesis are ineligible

- No concurrent treatment with angiotensin-converting-enzyme (ACE) inhibitors or
angiotensin II receptor blockers (ARBs)

- Uncontrolled intercurrent illness including, but not limited to ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, uncontrolled hypertension or hypotension, or psychiatric illness/social
situations that would limit compliance with study requirements

- Pregnant and nursing women are excluded from this study