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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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 Summary:

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.

Current Primary Outcome:

• Antitumor Activity as Assessed by Number of Patients Showing an Objective Tumor Response [ Time Frame: Approximately 1 year ]
  '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.
• Number of Participants Who Experienced Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 [ Time Frame: Approximately 1 year ]
  See the adverse event tables for specifics.

Original Primary Outcome:

• Antitumor activity as assessed by objective tumor response [ Time Frame: Approximately 1 year ]
  '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. 95% Confidence Intervals will be estimated. Fisher's exact and t-tests or Wilcoxon rank-sum tests used to assess the univariate associations of patient characteristics with response. Logistic regression used to determine which covariates are jointly predictive of response.
• Toxicity as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 [ Time Frame: Approximately 1 year ]
  95% Confidence Intervals will be estimated. The frequency and severity of all side effects and toxicities will be tabulated and analyzed using categorical techniques.

Current Secondary Outcome:

• Time to Disease Progression [ Time Frame: Approximately 5 years ]
• Overall Survival [ Time Frame: Approximately 5 years ]
• Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF) [ Time Frame: Day 1 ]
• Plasma Levels of Angiogenic Peptides Including PIGF [ Time Frame: Day 22 ]

Original Secondary Outcome: Same as current

Information By: Wake Forest University Health Sciences

Dates:
Date Received: March 9, 2012
Date Started: October 2009
Date Completion:
Last Updated: December 10, 2013
Last Verified: December 2013