Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This phase II trial studies how well trebananib works in treating patients with advanced angiosarcoma that cannot be removed by surgery. Trebananib may stop the growth of tumor cells by blocking blood flow to the tumor.

Further Study Information

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.

Eligibility Criteria

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

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Sandra D'Angelo

Principal Investigator

U.S.A.
Delaware
	Lewes
	Tunnell Cancer Center at Beebe Medical Center
		Stephen Scott Grubbs	Ph: 302-733-6227
	Newark
	Helen F. Graham Cancer Center at Christiana Hospital
		Stephen Scott Grubbs	Ph: 302-733-6227
District of Columbia
	Washington
	Washington Cancer Institute at Washington Hospital Center
		Dennis A Priebat	Ph: 202-877-8839
Hawaii
	Aiea
	Kapiolani Medical Center at Pali Momi
		Jeffrey L. Berenberg	Ph: 808-586-2979
		Jeffrey L. Berenberg	Ph: 808-586-2979
	Honolulu
	Cancer Research Center of Hawaii
		Jeffrey L. Berenberg	Ph: 808-586-2979
	Kapiolani Medical Center for Women and Children
		Jeffrey L. Berenberg	Ph: 808-586-2979
	OnCare Hawaii, Incorporated - Kuakini
		Jeffrey L. Berenberg	Ph: 808-586-2979
	OnCare Hawaii, Incorporated - Lusitana
		Jeffrey L. Berenberg	Ph: 808-586-2979
	Queen's Cancer Institute at Queen's Medical Center
		Jeffrey L. Berenberg	Ph: 808-586-2979
	Straub Clinic and Hospital, Incorporated
		Jeffrey L. Berenberg	Ph: 808-586-2979
	Kailua
	Castle Medical Center
		Jeffrey L. Berenberg	Ph: 808-586-2979
	Lihue
	Kauai Medical Clinic
		Jeffrey L. Berenberg	Ph: 808-586-2979
Illinois
	Bloomington
	St. Joseph Medical Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Bloomington%
	Illinois CancerCare - Bloomington
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Canton
	Illinois CancerCare - Canton
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Carthage
	Illinois CancerCare - Carthage
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Eureka
	Eureka Community Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Eureka
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Galesburg
	Galesburg Clinic, PC
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Havana
	Illinois CancerCare - Havana
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Kewanee
	Illinois CancerCare - Kewanee Clinic
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Macomb
	Illinois CancerCare - Macomb
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Monmouth
	Illinois CancerCare - Monmouth
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	OSF Holy Family Medical Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Normal
	BroMenn Regional Medical Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Community Cancer Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Community Cancer Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Ottawa
	Community Hospital of Ottawa
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Ottawa
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Pekin
	Cancer Treatment Center at Pekin Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Pekin
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Peoria
	CCOP - Illinois Oncology Research Association
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois CancerCare - Peoria
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Methodist Medical Center of Illinois
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	OSF St. Francis Medical Center
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Proctor Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Peru
	Illinois CancerCare - Princeton
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Illinois Valley Community Hospital
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Princeton
	Illinois CancerCare - Princeton
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Spring Valley
	Illinois CancerCare - Spring Valley
		Nguyet A Le-Lindqwister	Ph: 800-793-2262
	Urbana
	Carle Cancer Center at Carle Foundation Hospital
		Maria T Grosse-Perdekamp	Ph: 800-446-5532
			Email: kcheek@dmhhs.org
Indiana
	Indianapolis
	St. Francis Hospital Cancer Care Services
		Howard M. Gross	Ph: 317-783-8918
	Richmond
	Reid Hospital & Health Care Services
		Howard M. Gross	Ph: 317-783-8918
Iowa
	Iowa City
	Holden Comprehensive Cancer Center at University of Iowa
		Mohammed M Milhem	Ph: 800-237-1225
	Sioux City
	Mercy Medical Center - Sioux City
		Donald Bruce Wender	Ph: 712-252-0088
	Siouxland Hematology-Oncology Associates, LLP
		Donald Bruce Wender	Ph: 712-252-0088
	St. Luke's Regional Medical Center
		Donald Bruce Wender	Ph: 712-252-0088
Maryland
	Elkton MD
	Union Hospital of Cecil County
		Stephen Scott Grubbs	Ph: 302-733-6227
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Steven I Robinson	Ph: 507-538-7623
Missouri
	Saint Louis
	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
		Brian A Van Tine	Ph: 800-600-3606
			Email: info@siteman.wustl.edu
New Jersey
	Camden
	Cancer Institute of New Jersey at Cooper University Hospital - Camden
		Stephen Scott Grubbs	Ph: 302-733-6227
New York
	New York
	Memorial Sloan-Kettering Cancer Center
		Sandra P D'Angelo	Ph: 212-639-7202
Ohio
	Dayton
	CCOP - Dayton
		Howard M. Gross	Ph: 317-783-8918
	David L. Rike Cancer Center at Miami Valley Hospital
		Howard M. Gross	Ph: 317-783-8918
	Good Samaritan Hospital
		Howard M. Gross	Ph: 317-783-8918
	Grandview Hospital
		Howard M. Gross	Ph: 317-783-8918
	Samaritan North Cancer Care Center
		Howard M. Gross	Ph: 317-783-8918
	Findlay
	Blanchard Valley Regional Cancer Center
		Howard M. Gross	Ph: 317-783-8918
	Franklin
	Atrium Medical Center
		Howard M. Gross	Ph: 317-783-8918
	Greenville
	Wayne Hospital
		Howard M. Gross	Ph: 317-783-8918
	Kettering
	Charles F. Kettering Memorial Hospital
		Howard M. Gross	Ph: 317-783-8918
	Troy
	UVMC Cancer Care Center at Upper Valley Medical Center
		Howard M. Gross	Ph: 317-783-8918
	Xenia
	Ruth G. McMillan Cancer Center at Greene Memorial Hospital
		Howard M. Gross	Ph: 317-783-8918

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01623869
Information obtained from ClinicalTrials.gov on May 06, 2013

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