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

Phase 2

Completed

Conditions: Recurrent Adult Soft Tissue Sarcoma
Stage III Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma
Adult Angiosarcoma

Interventions: Other: Laboratory Biomarker Analysis
Biological: Trebananib

Registration Number: NCT01623869

Lead Sponsor: National Cancer Institute (NCI)

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 16

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (trebananib)	Laboratory Biomarker Analysis	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.
Treatment (trebananib)	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.

Primary Outcome Measures

Name	Time	Method
Confirmed Response Rate (CR or PR) Using RECIST	Up to 18 months	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: 1. Disappearance of all target and non-target lesions, 2. Each target lesion and non-target lymph node must have reduction in short axis to \<1.0 cm. Partial Response (PR): 1. 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. 2. 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.

Secondary Outcome Measures

Name	Time	Method
OS	From the date of registration to the date of death or the date of last follow-up, assessed up to 18 months	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.
Progression Free Survival (PFS)	From the start of treatment to time of radiologic or clinical progression or death, whichever occurs first, assessed up to 18 months	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.

Trial Locations

Locations (70): Perry Memorial Hospital
🇺🇸
Princeton, Illinois, United States
Illinois CancerCare-Carthage
🇺🇸
Carthage, Illinois, United States
Illinois CancerCare-Havana
🇺🇸
Havana, Illinois, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Northwestern University
🇺🇸
Chicago, Illinois, United States
Illinois CancerCare-Eureka
🇺🇸
Eureka, Illinois, United States
Carle Cancer Center
🇺🇸
Urbana, Illinois, United States
Saint Luke's Regional Medical Center
🇺🇸
Sioux City, Iowa, United States
Kettering Medical Center
🇺🇸
Kettering, Ohio, United States
Pali Momi Medical Center
🇺🇸
Aiea, Hawaii, United States
Oncare Hawaii Inc-POB II
🇺🇸
Honolulu, Hawaii, United States
Kapiolani Medical Center for Women and Children
🇺🇸
Honolulu, Hawaii, United States
Illinois CancerCare-Bloomington
🇺🇸
Bloomington, Illinois, United States
Saint Joseph Medical Center
🇺🇸
Bloomington, Illinois, United States
Illinois CancerCare-Canton
🇺🇸
Canton, Illinois, United States
Eureka Hospital
🇺🇸
Eureka, Illinois, United States
Illinois CancerCare Galesburg
🇺🇸
Galesburg, 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
Illinois CancerCare-Monmouth
🇺🇸
Monmouth, Illinois, United States
Mcdonough District Hospital
🇺🇸
Macomb, Illinois, United States
Community Cancer Center Foundation
🇺🇸
Normal, Illinois, United States
Bromenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
Holy Family Medical Center
🇺🇸
Monmouth, 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
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
Methodist Medical Center of Illinois
🇺🇸
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 CancerCare-Princeton
🇺🇸
Princeton, Illinois, United States
Illinois Valley Hospital
🇺🇸
Peru, Illinois, United States
Illinois CancerCare-Spring Valley
🇺🇸
Spring Valley, 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
Washington University School of Medicine
🇺🇸
Saint Louis, Missouri, United States
Grandview Hospital
🇺🇸
Dayton, Ohio, United States
Good Samaritan Hospital - Dayton
🇺🇸
Dayton, Ohio, United States
Samaritan North Health Center
🇺🇸
Dayton, Ohio, United States
Blanchard Valley Hospital
🇺🇸
Findlay, Ohio, United States
Dayton CCOP
🇺🇸
Dayton, Ohio, United States
Atrium Medical Center-Middletown Regional Hospital
🇺🇸
Franklin, Ohio, United States
Wayne Hospital
🇺🇸
Greenville, Ohio, United States
Upper Valley Medical Center
🇺🇸
Troy, Ohio, United States
Greene Memorial Hospital
🇺🇸
Xenia, Ohio, United States
Oncare Hawaii Inc-Pali Momi
🇺🇸
Aiea, Hawaii, United States
Queen's Medical Center
🇺🇸
Honolulu, Hawaii, United States
Straub Clinic and Hospital
🇺🇸
Honolulu, Hawaii, United States
Wilcox Memorial Hospital and Kauai Medical Clinic
🇺🇸
Lihue, Hawaii, United States
Oncare Hawaii Inc-Kuakini
🇺🇸
Honolulu, Hawaii, United States
Castle Medical Center
🇺🇸
Kailua, Hawaii, United States
University of Hawaii Cancer Center
🇺🇸
Honolulu, Hawaii, United States
Graham Hospital Association
🇺🇸
Canton, Illinois, United States
Memorial Sloan-Kettering Cancer Center
🇺🇸
New York, New York, United States
Miami Valley Hospital
🇺🇸
Dayton, Ohio, United States
Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Cooper Hospital University Medical Center
🇺🇸
Camden, New Jersey, United States
Christiana Care Health System-Christiana Hospital
🇺🇸
Newark, Delaware, United States
Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Union Hospital of Cecil County
🇺🇸
Elkton MD, Maryland, United States