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

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

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.

Study Overview

• Status: Completed
• Conditions: Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Adult Angiosarcoma
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Trebananib

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Hospital Center
  • Hawaii
    • Aiea, Hawaii, United States, 96701
      • Oncare Hawaii Inc-Pali Momi
    • Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Honolulu, Hawaii, United States, 96813
      • Oncare Hawaii Inc-POB II
    • Honolulu, Hawaii, United States, 96817
      • Oncare Hawaii Inc-Kuakini
    • Kailua, Hawaii, United States, 96734
      • Castle Medical Center
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
  • Illinois
    • Bloomington, Illinois, United States, 61704
      • Illinois CancerCare-Bloomington
    • Bloomington, Illinois, United States, 61701
      • Saint Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Illinois CancerCare-Canton
    • Canton, Illinois, United States, 61520
      • Graham Hospital Association
    • Carthage, Illinois, United States, 62321
      • Illinois CancerCare-Carthage
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Eureka, Illinois, United States, 61530
      • Illinois CancerCare-Eureka
    • Eureka, Illinois, United States, 61530
      • Eureka Hospital
    • Galesburg, Illinois, United States, 61401
      • Illinois CancerCare Galesburg
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Havana, Illinois, United States, 62644
      • Illinois CancerCare-Havana
    • Kewanee, Illinois, United States, 61443
      • Illinois CancerCare-Kewanee Clinic
    • Macomb, Illinois, United States, 61455
      • Illinois CancerCare-Macomb
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Monmouth, Illinois, United States, 61462
      • Illinois CancerCare-Monmouth
    • Monmouth, Illinois, United States, 61462
      • Holy Family Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center Foundation
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Illinois CancerCare-Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Illinois CancerCare-Ottawa Clinic
    • Ottawa, Illinois, United States, 61350
      • Ottawa Regional Hospital and Healthcare Center
    • Pekin, Illinois, United States, 61554
      • Illinois CancerCare-Pekin
    • Pekin, Illinois, United States, 61554
      • Pekin Cancer Treatment Center
    • Peoria, Illinois, United States, 61637
      • OSF Saint Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • Illinois CancerCare-Peoria
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61603
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61615
      • Illinois Oncology Research Association CCOP
    • Peru, Illinois, United States, 61354
      • Illinois CancerCare-Peru
    • Peru, Illinois, United States, 61354
      • Illinois Valley Hospital
    • Princeton, Illinois, United States, 61356
      • Illinois CancerCare-Princeton
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • Illinois CancerCare-Spring Valley
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Saint Francis Health-Indianapolis
    • Richmond, Indiana, United States, 47374
      • Reid Hospital and Health Care Services
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51104
      • Saint Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center-Sioux City
  • Maryland
    • Elkton MD, Maryland, United States, 21921
      • Union Hospital of Cecil County
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Hospital University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Ohio
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Health Center
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45420
      • Dayton CCOP
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Xenia, Ohio, United States, 45385
      • Greene Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Trebananib; Given IV; Other Names: AMG 386; Angiopoietin 1/2-Neutralizing Peptibody AMG 386

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed Response Rate (CR or PR) Using RECIST	Response and progression will be evaluated using the international RECIST guidelines (v1.1). Patients are evaluated every 8 weeks for disease status, with a subsequent 4 week assessment required to confirm a response. Complete Response (CR) - All of the following must be true: Disappearance of all target and non-target lesions,; Each target lesion and non-target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease from the baseline measurements of the sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation.; Persistence of one or more non-target lesions or non-target lymph nodes. The confirmed response rate is estimated as the number of patients having a CR or PR, divided by the number of eligible patients having at least one post-baseline assessment. The 95% confidence intervals provided using the method of Duffy and Santner.	Up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	Progression-free survival (PFS) is defined as the duration of time from the start of treatment to time of radiologic or clinical progression or death, whichever occurs first. PFS will be censored at most recent radiographic assessment date for patients remaining alive at the time of the statistical analysis. Kaplan-Meier methodology will be used to estimate the distribution of PFS.	From the start of treatment to time of radiologic or clinical progression or death, whichever occurs first, assessed up to 18 months
OS	Overall survival (OS) is the duration of time from the date of registration/randomization to the date of death or the date of last follow-up for patients who remain alive or who are lost to follow-up at the time of the analysis. Kaplan-Meier methodology will be used to estimate the distribution of OS.	From the date of registration to the date of death or the date of last follow-up, assessed up to 18 months

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sandra D'Angelo, Alliance for Clinical Trials in Oncology

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (ACTUAL): September 1, 2014
• Study Completion (ACTUAL): February 1, 2015

Study Registration Dates

• First Submitted: June 17, 2012
• First Submitted That Met QC Criteria: June 17, 2012
• First Posted (ESTIMATE): June 20, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): October 19, 2015
• Last Update Submitted That Met QC Criteria: September 28, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue; Sarcoma; Hemangiosarcoma; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Trebananib
• Other Study ID Numbers: NCI-2012-01978 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); CDR0000735380; CALGB-A091103; A091103 (OTHER: CTEP)