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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Comprehensive Cancer Center of Wake Forest University
ClinicalTrials.gov Identifier:
NCT01553539
First received: March 9, 2012
Last updated: December 10, 2013
Last verified: December 2013
  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.

Funding Source - FDA Office of Orphan Drug Products (OOPD)


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:


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

Primary Outcome Measures:
  • Antitumor Activity as Assessed by Number of Patients Showing an 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.

  • 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 ] [ Designated as safety issue: Yes ]
    See the adverse event tables for specifics.


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 ]

Enrollment: 20
Study Start Date: October 2009
Primary Completion Date: January 2013 (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/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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Principal Investigator: William Petty Wake Forest School of Medicine
  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, 003936-01A2
Study First Received: March 9, 2012
Results First Received: November 15, 2013
Last Updated: December 10, 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 July 22, 2014