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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
N/A
Open (Enrolling)
Both
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


PRIMARY OBJECTIVES:

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).

SECONDARY OBJECTIVES:

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

TERTIARY OBJECTIVES:

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
enrollment/randomization

- 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
surgery

- 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:

Interventional

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:

No

Principal Investigator

Sandra D'Angelo

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cancer and Leukemia Group B

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-01978

NCT ID:

NCT01623869

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

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021
Mayo ClinicRochester, Minnesota  55905
University of Iowa Hospitals and ClinicsIowa City, Iowa  52242
Washington University School of MedicineSaint Louis, Missouri  63110
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Beebe Medical CenterLewes, Delaware  19958
Memorial HospitalCarthage, Illinois  62321
Galesburg ClinicGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Proctor HospitalPeoria, Illinois  61614
Perry Memorial HospitalPrinceton, Illinois  61356
Grandview HospitalDayton, Ohio  45405
Eureka HospitalEureka, Illinois  61530
Graham Hospital AssociationCanton, Illinois  61520
Holy Family Medical CenterDes Plaines, Illinois  60016
Saint Joseph Medical CenterJoliet, Illinois  60435
Miami Valley HospitalDayton, Ohio  45409
Wayne HospitalGreenville, Ohio  45331
Greene Memorial HospitalXenia, Ohio  45385
Union Hospital of Cecil CountyElkton MD, Maryland  21921
Washington Hospital CenterWashington, District of Columbia  20010
Queen's Medical CenterHonolulu, Hawaii  96813
Northwestern UniversityChicago, Illinois  60611
Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701
Kapiolani Medical Center for Women and ChildrenHonolulu, Hawaii  96826
Straub Clinic and HospitalHonolulu, Hawaii  96813
Castle Medical CenterKailua, Hawaii  96734
OSF Saint Francis Medical CenterPeoria, Illinois  61637
Oncare Hawaii Inc-POB IIHonolulu, Hawaii  96813
Oncare Hawaii Inc-KuakiniHonolulu, Hawaii  96817
University of HawaiiHonolulu, Hawaii  96813
Community Cancer Center FoundationNormal, Illinois  61761
Illinois CancerCare-Ottawa ClinicOttawa, Illinois  61350
Ottawa Regional Hospital and Healthcare CenterOttawa, Illinois  61350
Pekin Cancer Treatment CenterPekin, Illinois  61554
Illinois Oncology Research Association CCOPPeoria, Illinois  61615
Illinois CancerCare-PeoriaPeoria, Illinois  61615
Illinois Valley HospitalPeru, Illinois  61354
Reid Hospital and Health Care ServicesRichmond, Indiana  47374
Mercy Medical Center-Sioux CitySioux City, Iowa  51104
Saint Luke's Regional Medical CenterSioux City, Iowa  51104
Cooper Hospital University Medical CenterCamden, New Jersey  08103
Good Samaritan Hospital - DaytonDayton, Ohio  45406
Dayton CCOPDayton, Ohio  45429
Samaritan North Health CenterDayton, Ohio  45415
Blanchard Valley HospitalFindlay, Ohio  45840
Atrium Medical Center-Middletown Regional HospitalFranklin, Ohio  45005-1066
Kettering Medical CenterKettering, Ohio  45429
Upper Valley Medical CenterTroy, Ohio  45373
Illinois CancerCare-BloomingtonBloomington%, Illinois  61701
Illinois CancerCare-CantonCanton, Illinois  61520
Illinois CancerCare-CarthageCarthage, Illinois  62321
Illinois CancerCare-EurekaEureka, Illinois  61530
Illinois CancerCare-HavanaHavana, Illinois  62644
Illinois CancerCare-Kewanee ClinicKewanee, Illinois  61443
Illinois CancerCare-MacombMacomb, Illinois  61455
Illinois CancerCare-MonmouthMonmouth, Illinois  61462
Illinois CancerCare-Community Cancer CenterNormal, Illinois  61761
Illinois CancerCare-PekinPekin, Illinois  61603
Illinois CancerCare-PeruPeru, Illinois  61354
Illinois CancerCare-PrincetonPrinceton, Illinois  61356
Illinois CancerCare-Spring ValleySpring Valley, Illinois  61362
Wilcox Memorial Hospital and Kauai Medical ClinicLihue, Hawaii  96766-1099
Siouxland Hematology Oncology AssociatesSioux City, Iowa  51101
Carle Foundation - Carle Cancer CenterUrbana, Illinois  61801
Franciscan St. Francis HealthIndianapolis, Indiana  46237
Christiana Care Health System-Christiana HospitalNewark, Delaware  19718
Oncare Hawaii Inc - Kapiolani Medical Center at Pali MomiAiea, Hawaii  96701