Angiotensin-(1-7) [Ang-(1-7)] is a first-in-class drug for treating cancer that functions as an agonist for the Gprotein coupled receptor, mas. Ang-(1-7) is endogenous hormone that has demonstrated anti-angiogenic properties in a variety of animal models. In cancer, Ang-(1-7) inhibits angiogenesis by both directly inhibiting endothelial cell proliferation and reducing the secretion of pro-angiogenic peptides from cancer cells. The Phase 2 study proposed in this application will examine the activity of this drug when given once a day continuously. The goals of the study are to establish the safety of this dosing schedule and assess the radiographic and biomarker activity. Completion of this study will lead to an improved understanding of the clinical benefits and adverse events associated with this treatment.

Public Health Relevance

The phase II study of Ang-(1-7) proposed in this grant is designed to study clinical outcomes, biomarker changes, and pharmacologic measures. This trial will enroll 20 patients at a dose of 20 mg once daily continuously. Based on the planned interim safety analysis of the first 10 patients and continuous review of safety data for 18 patients currently enrolled, it appears that this dose is very well tolerated. There has only been one serious adverse event attributed as possibly related to the Ang-(1-7) which was a grade 3, uncomplicated deep vein thrombosis (DVT). The dose de-escalation cohort of 20 additional patients will not be needed. Placental growth factor (PlGF) and other angiogenic biomarkers will be evaluated on day 1 and day 22. In addition, blood samples obtained on day 22 will be assessed to measure accumulation of the parent drug and its metabolites. Data and safety monitoring are critical for the safe conduct of this study and are discussed in the Research Design and Methods. This clinical trial will be facilitated by an established Clinical Research Management core facility that is supported by the Comprehensive Cancer Center of Wake Forest University (CCCWFU).

Agency
National Institute of Health (NIH)
Institute
Food and Drug Administration (FDA)
Type
Research Project (R01)
Project #
1R01FD003936-01A2
Application #
8358258
Study Section
Special Emphasis Panel (ZFD1-OPD-N (S1))
Project Start
2012-09-14
Project End
2014-08-31
Budget Start
2012-09-14
Budget End
2014-08-31
Support Year
1
Fiscal Year
2012
Total Cost
Indirect Cost
Name
Wake Forest University Health Sciences
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157