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

Recurrent Adult Soft Tissue Sarcoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01623869
• Other study ID #: NCI-2012-01978
• Secondary ID: NCI-2012-01978CD
• Status: Completed
• Phase: Phase 2
• First received: June 17, 2012
• Last updated: September 28, 2015
• Start date: July 2012
• Est. completion date: February 2015

Study information

• Verified date: June 2015
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 2015
• Est. primary completion date: September 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Other:
• Laboratory Biomarker Analysis
Correlative studies

Biological:
• Trebananib
Given IV

Locations

Country	Name	City	State
United States	Oncare Hawaii Inc-Pali Momi	Aiea	Hawaii
United States	Pali Momi Medical Center	Aiea	Hawaii
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Saint Joseph Medical Center	Bloomington	Illinois
United States	Cooper Hospital University Medical Center	Camden	New Jersey
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	Dayton CCOP	Dayton	Ohio
United States	Good Samaritan Hospital - Dayton	Dayton	Ohio
United States	Grandview Hospital	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Samaritan North Health Center	Dayton	Ohio
United States	Union Hospital of Cecil County	Elkton MD	Maryland
United States	Eureka Hospital	Eureka	Illinois
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Blanchard Valley Hospital	Findlay	Ohio
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Illinois CancerCare Galesburg	Galesburg	Illinois
United States	Wayne Hospital	Greenville	Ohio
United States	Illinois CancerCare-Havana	Havana	Illinois
United States	Mason District Hospital	Havana	Illinois
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Oncare Hawaii Inc-Kuakini	Honolulu	Hawaii
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	Franciscan Saint Francis Health-Indianapolis	Indianapolis	Indiana
United States	University of Iowa/Holden Comprehensive Cancer Center	Iowa City	Iowa
United States	Castle Medical Center	Kailua	Hawaii
United States	Kettering Medical Center	Kettering	Ohio
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Beebe Medical Center	Lewes	Delaware
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
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	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	Christiana Care Health System-Christiana Hospital	Newark	Delaware
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	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Illinois Oncology Research Association CCOP	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	OSF Saint Francis Medical Center	Peoria	Illinois
United States	Proctor Hospital	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	Reid Hospital and Health Care Services	Richmond	Indiana
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Mercy Medical Center-Sioux City	Sioux City	Iowa
United States	Saint Luke's Regional Medical Center	Sioux City	Iowa
United States	Siouxland Regional Cancer Center	Sioux City	Iowa
United States	Illinois CancerCare-Spring Valley	Spring Valley	Illinois
United States	Upper Valley Medical Center	Troy	Ohio
United States	Carle Cancer Center	Urbana	Illinois
United States	Washington Hospital Center	Washington	District of Columbia
United States	Greene Memorial Hospital	Xenia	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No