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Phase II Study of the Angiopoietin-1 and -2 Peptibody AMG 386 for the Treatment of Angiosarcoma

Phase 2
18 Years
Open (Enrolling)
Adult Angiosarcoma, Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma

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Trial Information

Phase II Study of the Angiopoietin-1 and -2 Peptibody AMG 386 for the Treatment of Angiosarcoma


I. To determine the overall response rate (ORR), defined as complete response (CR) +partial
response (PR), in patients with advanced, unresectable angiosarcoma treated with trebananib
(AMG 386).


I. To evaluate the progression-free survival (PFS) and overall survival (OS) of patients
with advanced, unresectable angiosarcoma treated with AMG 386.


I. To correlate ORR, PFS, and OS with: Baseline and post-treatment changes in expression of
angiopoietin 2 (Ang2) and TEK tyrosine kinase, endothelial (Tie2) by immunohistochemistry
(IHC); Serum levels of angiopoietin 1 (Ang1) and Ang2; Baseline and post-treatment changes
in phospho-receptor tyrosine kinase status of TIE2, vascular endothelial growth factor
receptor 2 (VEGFR-2), phosphatidylinositol 3 kinase (PI3K), mitogen-activated protein kinase
Inhibitor (MEK) in tumor tissue; Mutational status of VEGFR-2 and amplification of v-myc
myelocytomatosis viral oncogene homolog (avian) (MYC)/fms-related tyrosine kinase 4 (FLT4).

OUTLINE: This is a multicenter study.

Patients receive trebananib IV over 30-60 minutes on days 1, 8, 15, and 22. Courses repeat
every 28 days in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood sample collection at baseline and periodically during treatment
for correlative studies. Tumor tissue samples may be also collected.

After completion of study treatment, patients are followed up for 4 weeks and then every 6
months for 18 months.

Inclusion Criteria:

- Patients must have histologically confirmed angiosarcoma that is unresectable

- Patients must have measurable disease per Response Evaluation Criteria in Solid
Tumors(RECIST) 1.1, defined as at least one lesion that can be accurately measured in
at least one dimension (longest diameter to be recorded for non-nodal lesions and
short axis for nodal lesions) as >= 2 cm with conventional techniques or as >= 1 cm
with spiral computed tomography (CT) scan, magnetic resonance imaging (MRI), or
calipers by clinical exam

- Patients must have had =< 4 prior systemic treatment regimens

- Eastern Cooperative Oncology Group (ECOG) 0-1 or Karnofsky >= 70%

- Life expectancy of greater than 3 months

- Leukocytes >= 3,000/mcL

- Absolute neutrophil count >= 1,500/mcL

- Hemoglobin >= 8.5g/dL

- Platelet count >= 60,000/mcL

- Total bilirubin =< 1.5 times institutional upper limit of normal (ULN)

- Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase [SGOT]) =<
2.5 times institutional ULN

- Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase[SGPT]) =< 2.5
times institutional ULN

- Partial thromboplastin time (PTT) or activated (a)PTT =< 1.5 times ULN per
institutional laboratory range

- International normalized ratio(INR) =< 1.5 (unless on warfarin)

- Creatinine =< 1.5 times ULN OR creatinine clearance > 40 mL/min per 24-hour urine
collection or calculated according to the Cockcroft-Gault formula

- Urinary protein =< 30 mg/dL in urinalysis or =< 1+ on dipstick, unless quantitative
protein is < 1,000 mg in a 24-hour urine sample

- Women of childbearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control; abstinence) prior to study entry and
for the duration of study participation

- Women of child-bearing potential and men must agree to use adequate
contraception (hormonal or 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 she or her partner is participating in
this study, she should inform her treating physician immediately

- Because there is an unknown but potential risk for adverse events in nursing
infants secondary to treatment of the mother with AMG 386, breastfeeding must be
discontinued if the mother is treated with AMG 386; these potential risks may
also apply to other agents used in this study

- Female of childbearing potential is defined as the following: A female of
childbearing potential is a sexually mature woman who: 1) has not undergone a
hysterectomy or bilateral oophorectomy or 2) has not been naturally
postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had menses
at any time in the preceding 24 consecutive months)

- Generally well-controlled blood pressure with systolic blood pressure =< 150 mm Hg
and diastolic blood pressure =< 90 mm Hg (Note: The use of anti-hypertensive
medications to control hypertension is permitted)

- Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

- No known history of brain metastases

- History of clinically significant bleeding within 6 months of

- No unresolved toxicities from prior systemic therapy that are CTCAE version 4.0 >=
grade 2 in severity except alopecia

- Currently or previously treated with AMG 386, or other molecules that inhibit the
angiopoietins or Tie2 receptor

- Clinically significant cardiovascular disease within 12 months prior to
enrollment/randomization, including myocardial infarction, unstable angina, grade 2
or greater (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0)
peripheral vascular disease, cerebrovascular accident, transient ischemic attack,
congestive heart failure, or arrhythmias not controlled by outpatient medication or
placement of percutaneous transluminal coronary angioplasty/stent

- Major surgery within 28 days prior to enrollment or still recovering from prior

- Treatment within 30 days prior to enrollment with strong immune modulators including,
but not limited to, systemic cyclosporine, tacrolimus, sirolimus, mycophenolate
mofetil, methotrexate, azathioprine, rapamycin, thalidomide, lenalidomide, and
targeted immune modulators such as abatacept (CTLA-4- -Ig),adalimumab, alefacept,
anakinra, belatacept (LEA29Y), efalizumab, etanercept, infliximab, or rituximab

- Non-healing wound

- Subject not consenting to the use of highly effective contraceptive precautions
(e.g., double barrier method [i.e., condom plus diaphragm]) during the course of the
study and for 6 months after administration of the last study medication

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to AMG 386

- History of allergic reactions to bacterially-produced proteins

- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
nitrosoureas or mitomycin C) prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Patients who have not yet completed at least 21 days (30 days for prior monoclonal
antibody therapy) since ending other investigational device or drug trials, or who
are currently receiving other investigational treatments

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Non-pregnant, non-nursing; Note: Women of child bearing potential must have a
pregnancy test, serum based within 7 days prior to registration; this is because AMG
386 is an inhibitor of angiogenesis with the potential for teratogenic or
abortifacient effects

- Patients with a history of venous or arterial thromboembolism within 12 months prior
to enrollment/randomization should be excluded

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Confirmed response rate (CR or PR) using RECIST

Outcome Description:

The 95% confidence intervals should be provided using the method of Duffy and Santner.

Outcome Time Frame:

Up to 18 months

Safety Issue:


Principal Investigator

Sandra D'Angelo

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B


United States: Food and Drug Administration

Study ID:




Start Date:

July 2012

Completion Date:

Related Keywords:

  • Adult Angiosarcoma
  • Recurrent Adult Soft Tissue Sarcoma
  • Stage III Adult Soft Tissue Sarcoma
  • Stage IV Adult Soft Tissue Sarcoma
  • Hemangiosarcoma
  • Sarcoma



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