Clinical trial NCT01553539: Therapeutic Angiotensin-(1-7) in Treating Patients With Metastatic Sarcoma That Cannot Be Removed By Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2012-03-14
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Antitumor Activity as Assessed by Number of Patients Showing an Objective Tumor Response
timeFrame: Approximately 1 year
measure: Number of Participants Who Experienced Adverse Events as Assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
timeFrame: Approximately 1 year
Secondary outcomes:
measure: Time to Disease Progression
timeFrame: Approximately 5 years
measure: Overall Survival
timeFrame: Approximately 5 years
measure: Plasma Levels of Angiogenic Peptides Including Placental Growth Factor (PlGF)
timeFrame: Baseline and Day 22
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: William Petty
role: PRINCIPAL_INVESTIGATOR
References: