Trebananib in Treating Patients With Advanced Angiosarcoma That Cannot Be Removed by Surgery

NCT ID: NCT01623869

Last Updated: 2015-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2015-02-28

Brief 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.

Detailed Description

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:

Patients receive trebananib intravenously (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.

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

Conditions

Adult Angiosarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (trebananib)

Patients receive 30 mg/kg 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.

Group Type: EXPERIMENTAL

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Trebananib

Intervention Type: BIOLOGICAL

Given IV

Interventions

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Trebananib

Given IV

Intervention Type: BIOLOGICAL

Other Intervention Names

AMG 386; Angiopoietin 1/2-Neutralizing Peptibody AMG 386

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
• 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 Common Terminology Criteria for Adverse Events (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 (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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sandra D'Angelo

Role: PRINCIPAL_INVESTIGATOR

Alliance for Clinical Trials in Oncology

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Cooper Hospital University Medical Center

Camden, New Jersey, United States

Beebe Medical Center

Lewes, Delaware, United States

Christiana Care Health System-Christiana Hospital

Newark, Delaware, United States

Washington Hospital Center

Washington D.C., District of Columbia, United States

Oncare Hawaii Inc-POB II

Honolulu, Hawaii, United States

Queen's Medical Center

Honolulu, Hawaii, United States

Straub Clinic and Hospital

Honolulu, Hawaii, United States

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Oncare Hawaii Inc-Kuakini

Honolulu, Hawaii, United States

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Castle Medical Center

Kailua, Hawaii, United States

Wilcox Memorial Hospital and Kauai Medical Clinic

Lihue, Hawaii, United States

Oncare Hawaii Inc-Pali Momi

‘Aiea, Hawaii, United States

Pali Momi Medical Center

‘Aiea, Hawaii, United States

Saint Joseph Medical Center

Bloomington, Illinois, United States

Illinois CancerCare-Bloomington

Bloomington, Illinois, United States

Graham Hospital Association

Canton, Illinois, United States

Illinois CancerCare-Canton

Canton, Illinois, United States

Illinois CancerCare-Carthage

Carthage, Illinois, United States

Memorial Hospital

Carthage, Illinois, United States

Northwestern University

Chicago, Illinois, United States

Eureka Hospital

Eureka, Illinois, United States

Illinois CancerCare-Eureka

Eureka, Illinois, United States

Illinois CancerCare Galesburg

Galesburg, Illinois, United States

Illinois CancerCare-Havana

Havana, Illinois, United States

Mason District Hospital

Havana, Illinois, United States

Illinois CancerCare-Kewanee Clinic

Kewanee, Illinois, United States

Illinois CancerCare-Macomb

Macomb, Illinois, United States

Mcdonough District Hospital

Macomb, Illinois, United States

Holy Family Medical Center

Monmouth, Illinois, United States

Illinois CancerCare-Monmouth

Monmouth, Illinois, United States

Bromenn Regional Medical Center

Normal, Illinois, United States

Community Cancer Center Foundation

Normal, Illinois, United States

Illinois CancerCare-Community Cancer Center

Normal, Illinois, United States

Illinois CancerCare-Ottawa Clinic

Ottawa, Illinois, United States

Ottawa Regional Hospital and Healthcare Center

Ottawa, Illinois, United States

Illinois CancerCare-Pekin

Pekin, Illinois, United States

Pekin Cancer Treatment Center

Pekin, Illinois, United States

Methodist Medical Center of Illinois

Peoria, Illinois, United States

Proctor Hospital

Peoria, Illinois, United States

Illinois CancerCare-Peoria

Peoria, Illinois, United States

Illinois Oncology Research Association CCOP

Peoria, Illinois, United States

OSF Saint Francis Medical Center

Peoria, Illinois, United States

Illinois CancerCare-Peru

Peru, Illinois, United States

Illinois Valley Hospital

Peru, Illinois, United States

Illinois CancerCare-Princeton

Princeton, Illinois, United States

Perry Memorial Hospital

Princeton, Illinois, United States

Illinois CancerCare-Spring Valley

Spring Valley, Illinois, United States

Carle Cancer Center

Urbana, Illinois, United States

Franciscan Saint Francis Health-Indianapolis

Indianapolis, Indiana, United States

Reid Hospital and Health Care Services

Richmond, Indiana, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

Siouxland Regional Cancer Center

Sioux City, Iowa, United States

Mercy Medical Center-Sioux City

Sioux City, Iowa, United States

Saint Luke's Regional Medical Center

Sioux City, Iowa, United States

Union Hospital of Cecil County

Elkton MD, Maryland, United States

Mayo Clinic

Rochester, Minnesota, United States

Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Grandview Hospital

Dayton, Ohio, United States

Good Samaritan Hospital - Dayton

Dayton, Ohio, United States

Miami Valley Hospital

Dayton, Ohio, United States

Samaritan North Health Center

Dayton, Ohio, United States

Dayton CCOP

Dayton, Ohio, United States

Blanchard Valley Hospital

Findlay, Ohio, United States

Atrium Medical Center-Middletown Regional Hospital

Franklin, Ohio, United States

Wayne Hospital

Greenville, Ohio, United States

Kettering Medical Center

Kettering, Ohio, United States

Upper Valley Medical Center

Troy, Ohio, United States

Greene Memorial Hospital

Xenia, Ohio, United States

Countries

United States

Other Identifiers

NCI-2012-01978

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000735380

Identifier Type: -

Identifier Source: secondary_id

CALGB-A091103

Identifier Type: -

Identifier Source: secondary_id

A091103

Identifier Type: OTHER

Identifier Source: secondary_id

A091103

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-01978

Identifier Type: -

Identifier Source: org_study_id