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

Purpose

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

Condition	Intervention	Phase
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	Drug: therapeutic angiotensin-(1-7) Other: laboratory biomarker analysis	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
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

Resource links provided by NLM:

MedlinePlus related topics: Bone Cancer Cancer Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by Comprehensive Cancer Center of Wake Forest University:

Primary Outcome Measures:

Antitumor activity as assessed by objective tumor response [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]
'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 ] [ Designated as safety issue: Yes ]
95% Confidence Intervals will be estimated. The frequency and severity of all side effects and toxicities will be tabulated and analyzed using categorical techniques.

Secondary Outcome Measures:

Time to disease progression [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
Plasma levels of angiogenic peptides including placental growth factor (PlGF) [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
Plasma levels of angiogenic peptides including PIGF [ Time Frame: Day 22 ] [ Designated as safety issue: No ]

Estimated Enrollment:	20
Study Start Date:	October 2009
Estimated Primary Completion Date:	October 2015 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Treatment (antiangiogenesis therapy) Patients receive therapeutic angiotensin-(1-7) SC once daily in the absence of disease progression or unacceptable toxicity.	Drug: therapeutic angiotensin-(1-7) Given SC Other Names: therapeutic Ang-(1-7) TXA127 Other: laboratory biomarker analysis Correlative study

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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/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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01553539

Locations

United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157

Sponsors and Collaborators

Comprehensive Cancer Center of Wake Forest University

National Cancer Institute (NCI)

Investigators

Principal Investigator:

William Petty

Wake Forest University

More Information

No publications provided

Responsible Party:	Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:	NCT01553539 History of Changes
Obsolete Identifiers:	NCT00974545
Other Study ID Numbers:	CCCWFU 71108, NCI-2009-01259
Study First Received:	March 9, 2012
Last Updated:	March 25, 2013
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Bone Neoplasms
Osteosarcoma
Chondrosarcoma
Sarcoma, Clear Cell
Sarcoma
Neoplasms by Site
Neoplasms
Bone Diseases
Musculoskeletal Diseases

Neoplasms, Bone Tissue
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Angiotensin I (1-7)
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 22, 2013