First Name
Allison
Last Name
Aguado
Degree
MD
Address
3333 Burnet Avenue MLC 5031
Cincinnati, OH 45229
United States
Phone Number
(513) 636-6695
Fax
(513) 636-3754
Email
Allison.Aguado@cchmc.org
Upload Cover Letter
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Investigator/Applicant Allison
First Name
Investigator/Applicant Aguado
Last Name
Investigator/Applicant MD
Degree
Investigator/Applicant
Name Address
Allison Aguado, MD 3333 Burnet Avenue, MLC 5031
Cincinnati, OH 45229
United States
Investigator/Applicant (513) 636-6695
Name Phone Number
Investigator/Applicant Allison.Aguado@cchmc.org
Name Email
Title
Phase I study of transarterial radioembolization with yttrium-90 (TARE-Y90)
utilizing Therasphere® in children with unresectable primary or secondary liver
malignancy
Abstract of Proposed Research Plan (300 words)
Liver tumors account for only 0.5-2% of cancer in children. Pediatric tumors tend to be exquisitely
radiosensitive, but the use of external beam radiation in young children could result in significant long
term toxicity such as growth retardation or adverse organ function. Conventional chemotherapy and
surgical resection or transplantation can cure some affected
children; the majority of HCCs, however, remain unresectable or incurable.
TARE-Y90 has been used extensively in adults to treat primary and secondary malignancies of the liver,
however
experience with TARE-Y90 in children is very limited, primarily due to the specialized equipment and
expertise required for its safe use. TARE-Y90 allows extremely high radiation doses to be delivered to
tumors supplied by the hepatic artery, with a relatively low incidence of radioembolization-induced liver
disease (REILD).
We hypothesize that, once the safety of TARE-Y90 is established in children, it could be considered as an
adjunctive therapy and potentially used to convert unresectable tumors or as a bridge to transplant. In
order to address this hypothesis, we propose the following aims
Specific Aim 1: To determine the safety, toxicity, and complication rate of transarterial radioembolization
with yttrium-90 (TARE-Y90) in children with unresectable primary or secondary liver malignancy.
Specific Aim 2: To collect preliminary evidence of clinical efficacy of TARE-Y90 in children with
unresectable primary or secondary liver malignancy. This will be evaluated by Hepatic Progression Free
Survival.
The anticipated number of patients would be 12, with planned trial duration of 3 years. Our Institution and
research team is uniquely suited to performing this research, as CCHMC serves as a referral center for
HCC and therefore we have the largest patient population and best expertise to successfully complete the
proposed study.
Upload: Detailed plan
and bibliography
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Resources and Environment:
Imaging Facilities: As members of the Department of Radiology’s Imaging Research Center (IRC), CPIR
faculty members, staff, and students have access to all IRC and clinical Radiology infrastructure, including
six, state-of-the-art imaging instruments dedicated to research activities including 3T and 1.5T wholebody MR scanners and a state-of-the-art cath lab for large animal research. The 3T and 1.5T
instrumentation (Philips Achieva and Ingenia, respectively) are housed in 1,400 ft2 of dedicated laboratory
space and share a common control room. The 1.5T system is interconnected with
the large animal cath lab, housing a Philips FD-20 system, for multi-modality interventions. The IRC’s InVivo MicroImaging Laboratory (IVML) is a 1,436 ft2 space, housing a 7.0T, 30-cm-bore Bruker Biospec MRI
system (Bruker BioSpin MRI GmbH, Ettlingen, Germany). It also houses a 1.5T extremity scanner (GE
Healthcare, Waukesha WI) modified for preclinical use and also serves as the engineering prototype for the
CCHMC-developed MRI system installed in the Neonatal Intensive Care Unit (NICU). Finally, the lab houses
an ImTek micro-CT system (ImTek, Inc. Knoxville, TN) for scanning small animals.
IRC Electronics Laboratory: This previously funded Core facility consists of a 700 ft2 lab space allocated
for electronic instrumentation used to design and construction of custom MRI coils and related hardware.
It is equipped with two HP Network analyzers (8751A, 3577A), HP spectrum analyzer (8560E), WaveTek
function generator (148A), sweep oscillators (1062), electronic frequency counter (HP 5328A), Tektronix
analog oscilloscope (2445B), Guardian 6100 safety analyzer, and Lecroy digital oscilloscope (9354AM).
This lab maintains an inventory of MR compatible capacitors, pure copper wire and tape, and other
components needed for custom RF coil fabrication. It also houses a
hood and etching facility for PC board fabrication.
IRC Machine Shop: This 450 ft2 space houses an Enco lathe, Bridgeport milling machine, Jet belt sander,
Wilton band saw, Dewalt power miter saw, Delta drill press, an LPKF circuit board milling machine, and
numerous power hand tools needed for the fabrication of MRI apparatus for human and animal research.
This shop maintains and inventory of Plexiglass™ and Lexan™ stock for this
purpose. The shop and several permanent staff members are available for construction of experimental
apparatus.
Clinical:
CCHMC has a vibrant clinical research infrastructure available for clinical and translational research
projects
across campus. It is a member of the Clinical Translational Sciences Awards consortium (CTSA),
creating new research programs and pathways, and leveraging of facilities to enhance clinical and
translational research conduct across CCHMC and UC.
2014 statistics regarding the breadth of CCHMC research and training are provided below.
• The total number of CCHMC faculty is approximately 950 (Pediatrics 741, Surgery 104, anesthesiology
56, radiology 49, patient services 3).
• The total number of clinical fellows = 243
• Total number of research post-doctoral fellows = 183
• The total number of residents = 395, with 118 in Pediatrics and 27 in Medicine/Pediatrics
• The total number of students rotating through CCHMC in 2014 was 185. The total number of summer
students was 193.
CCHMC provides a fantastic collaborative and cohesive research environment, which facilitates the
activities of the CF-RDP. In FY2014, the extramural grant support was $200,158,852 ($151,167,306 direct
costs). > 75% of this funding was from the NIH. In addition, over $56 million were donated to CCHMC in
2014 in various philanthropic gifts. Over 1700 peer reviewed articles were published (of >2000 total
publications). Standing slots in the schedule are reserved for research several
days during the week. Night and weekend access for research is also routinely available. The department
of Radiology is committed to providing sufficient access to these scanners for IRC researchers.
Computer:
Storage and Computer Network - Scanners and workstations are inter-connected on an institution-wide,
1GB/sec Ethernet network.
Computing Linux Clusters:
Total of 350 CPU Cores
Over 800 GB of Memory
100TB Fibre Channel SAN
Storage Servers: 55 TB of total storage space
4 Apple OS X XServe
1 HP-Windows 2003 Server
1 Dell CentOS Backup Server
2 Spectra Logic Tape Backup Libraries: 350 TB of compressed tape storage capacity
Workstations:
55 Windows
28 Mac OS
5 SGI
3 Solaris
15 Linux (includes magnets)
Additionally there are two dedicated workstation with Amira software licenses (Visualization Sciences
Group, Bordeaux, France) for quantitative image analysis. Further, the CPIR and IRC have developed a wide
range of custom software for image analysis in MATLAB (The MathWorks, Inc.) and R languages.
Clinical Trial Support:
The Clinical Management & Research Support Core (CMRSC) provides expertise in the management of the
Divisions of Hematology, Oncology and BMT’s clinical trials, from protocol development through study
closure. The team of principal investigators, clinical research coordinators, clinical research nurses,
advance practice nurses, data management specialists, medical writers, and administrative support
personnel provides a high level of support in the operation of all types of clinical trials, from translational
and early phase trials to larger phase III trials. In addition, the Translational Research Trials Office (TRTO)
provides the regulatory support for IND submission and regulatory submissions to the FDA and RAC. This
trial will benefit from the clinical trials
resources and facilities available from TRTO and CMRSC.
CTSA: CCHMC and University of Cincinnati have an NCCR funded Center for Clinical and Translational
Science and Training (CCTST), which was established in 2005 as CCHMC and UC’s academic home for
clinical and translational research. The Translational Research Trials Office (TRTO) under the auspices of
the CCTST will serve as the SDMC for pilot translational studies.
The GCRC also falls under the CCTST and has the following available resources supporting research
in children and adults include a 12-bed inpatient/12-room outpatient (including 4 beds for sleep
research), 11,000 sq. ft. unit on the CCHMC main campus, and the 36-bed inpatient/18-room outpatient,
53,500 sq. ft. Cincinnati Center for Clinical Research on the CCHMC Oak campus. A 3,000 sq. ft. satellite
location at the Cincinnati VA Medical Center includes 2 inpatient beds with cardiac monitoring capabilities,
4 outpatient rooms, and 3 procedure rooms. Planned additional services include “scatter bed” support and
broader outpatient support beyond the GCRC to include University and Holmes Hospitals, the Barrett
Cancer Center, University
of Cincinnati, the Drake Center rehabilitation hospital, and community hospitals. Core services are
offered in biochemistry, body composition, behavioral science, and bionutrition.
Major Equipment:
For use in this study
Y90 Therasphere or Sirsphere are commercially available and will be purchased from their respective
suppliers as listed below.
• TheraSphere® is approved by the U.S. Food and Drug Administration (FDA) under a Humanitarian Device
Exemption (HDE). It isd produced by BTG International ltd http://www.btg-im.com/
• SIR-Spheres microspheres are manufactured by Sirtex Medical Limited which has its headquarters in
Sydney, Australia and U.S. operations in Woburn, Massachusetts.
http://www.sirtex.com/us/clinicians/about-sir-spheres-microspheres/
Fluoroscopy - Philips Allure Xper FD20. Available for this study in the Fluoroscopy Suite at CCHMC, with
trained technicians and appropriate software for image analysis and manipulation. The 2k digital imaging
chain of the Allura Xper FD20 fixed X-ray system provides virtually distortion-free visualization of small
details and objects to support endovascular surgery, including AAA and
carotid stenting procedures. Advanced X-ray dose reduction features reduce radiation exposure for
patients and staff. Fixed X-ray system features automated settings and table-side controls that
help clinicians focus on the patient and the procedure
Live 3D image guidance tools provide extra support for complex minimally invasive procedures in the
hybrid room. DoseWise offers low X-ray dose and excellent image quality Table tilt and cradle movement
enable optimal patient positioning for more invasive or needle
guided puncture procedures
PET/CT - Philips Ingenuitiy TF scanner. Available for this study in the Fluoroscopy Suite at CCHMC, with
trained technicians and appropriate software for image analysis and manipulation.
Combining the high-fidelity imaging performance of Astonish TF with the latest in Ingenuity CT
innovation, including iDose4, iPatient and SyncRight, Ingenuity TF offers high image quality, fast scans,
and the ability to choose the right dose – without compromise. Astonish TF is the next evolution in Timeof-Flight (TOF) technology. With up to 30% improved contrast over non-TOF, Astonish TF provides
enhanced lesion detectability with reconstruction speeds as fast as 30 seconds/bed. The system also
features iDose4, an iterative reconstruction technique that gives you control of the dial so you can
personalize image quality based on your patients’ needs at low dose.
Full-fidelity imaging accuracy with PET imaging utilizes full listmode capabilities, allowing for fast scans,
and exceptional image quality that combine to provide greater accuracy in quantitative assessment.
Other equipment available
General Electric 1.5 Tesla MR scanners: Researchers and collaborators of the IRC and CPIR enjoy research
access to three 1.5 T GE MR imaging scanners located in the clinical section of the hospital. Standing slots
in the schedule are reserved for research several days during the week. Night and weekend access for
research is also routinely available. Two of the scanners are installed in fixed suites and operate with 15.0
M4 software. The third GE scanner is in a mobile trailer and operates with 12.0 software. One of the fixedsite scanners has a gradient slew rate of 120 mT/m/ms. The other fixed-site scanner and the mobile
scanner have a slew rate of 77 mT/m/ms. The GE MR scanners feature actively
shielded, super-conducting magnets and a comprehensive collection of surface coils. The Department of
Radiology is committed to providing sufficient access to these scanners to permit the
investigators to develop and test the new hardware and software described in this proposal as needed.
Siemens 1.5 Tesla MR scanner: Researchers and collaborators of the IRC and CPIR enjoy research
access to a Siemens Espree MRI scanner located in the interventional suites of the hospital. Standing slots
in the schedule are reserved for research several days during the week. This wide-bore scanner features
an actively shielded, super-conducting magnet with a comprehensive collection of surface coils. The
Department of Radiology is committed to providing sufficient access to this scanner to permit the
investigators to develop and test the new hardware and software described in this proposal.
Philips Achieva 3.0T X-series MRI scanner: The Department of Radiology has a 3.0T Philips MR
scanner that is identical to the one in the IRC. Researchers and collaborators of the IRC and CPIR have
standing slots in the schedule for this scanner.
ONI 1.5T MRI scanner Radiology has a 1.5T extremity MR scanner in the NICU —identical to the one
installed in the IRC—that is operated as a satellite operation of the department. The scanner has a
gradient set capable of 70 mT/m gradient pulses with a slew rate of 300 mT/m/ms. It also has identical
coil plugs to the large-bore magnets in the main Department of Radiology and the IRC neonate magnet,
permitting the development and use of common coils for these scanners. The scanner has 16 receive
channels and interchangeable volume coils to facilitate coil development and optimal
coil designs. Because of its location, the NICU scanner is
reserved exclusively for NICU patients.
Award Payee First
Melissa
Name
Award Payee Last
Name
Knight
Award Payee Address
Cincinnati Children's Hospital Medical Center 3333 Burnet Avenue, MLC 7030
Cincinnati, OH 45229
United States
Award Payee Phone
(513) 636-7744
Number
Award Payee Email
sponsoredprograms@cchmc.org
Grant Administrator's
Aren
First Name
Grant Administrator's
Enderle
Last Name
Grant Administrator's
Address
Children's Hospital Research Foundation 3333 Burnet Avenue, MLC 7030
Cincinnati, OH 45229
United States
Grant Administrator's
(513) 636-8874
Phone Number
Grant Administrator's
sponsoredprograms@cchmc.org
Email
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Vitae
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