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

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well therapeutic angiotensin-(1-7) works as second-line therapy or third-line therapy in treating patients with metastatic sarcoma that cannot be removed by surgery. Therapeutic angiotensin-(1-7) may stop the growth of sarcoma by blocking blood flow to the tumor. Funding Source - FDA Office of Orphan Drug Products (OOPD)

Detailed Description
-----------------
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.

Official Title
-----------------
A Phase II Clinical Trial of Angiotensin 1-7 For the Second or Third Line Treatment of Patients With Metastatic or Unresectable Sarcomas

Conditions
-----------------
Bone Cancer, Chondrosarcoma, Clear Cell Sarcoma of the Kidney, Metastatic Osteosarcoma, Ovarian Sarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Osteosarcoma, Recurrent Uterine Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage III Uterine Sarcoma, Stage IV Adult Soft Tissue Sarcoma, Stage IV Uterine Sarcoma

Intervention / Treatment
-----------------
* Drug: therapeutic angiotensin-(1-7)
* Other: laboratory biomarker analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (antiangiogenesis therapy)<br>Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity. | Drug: therapeutic angiotensin-(1-7)<br>* Given SC<br>* Other names: TXA127;Other: laboratory biomarker analysis<br>* Correlative study<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antitumor Activity as Assessed by Number of Patients Showing an Objective Tumor Response | 'Activity' will be operationalized using objective tumor response, which will be estimated as the proportion of partial and complete responders (according to Response Evaluation Criteria in Solid Tumors [RECIST] criteria) among all evaluable patients. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. | Approximately 1 year | 
| Number of Participants Who Experienced Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 | See the adverse event tables for specifics. | Approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression |  | Approximately 5 years | 
| Overall Survival |  | Approximately 5 years | 
| Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) |  | Baseline and Day 22 |