A Phase II Study Using LC Bead LUMI Radio-Opaque Embolic Beads to Detect and Characterize the Vascularity of Hepatic Tumors During Treatment With Transarterial Embolization (TAE) Alone or Combined With Thermal Ablation
Phase: NA
Conditions: Hepatic Cancer, Liver Neoplasms, Hepatocellular Cancer, Liver Cancer
Sponsor: National Institutes of Health Clinical Center (CC)

Abbreviated Title:  RFA + TACE with RO Beads
Version Date:  04/13/2018
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Abbreviated Title: RFA + TACE with RO Beads
CC Protocol #: 16-CC-0049 C
NCI Version Date: 04/13/2018
NCT Number:  NCT02649868
A Phase II Study using LC Bead LUMI Radio-Opaque Embolic Beads to Detect and 
Characterize the Vascularity of Hepatic Tumors during Treatment with Transarterial 
Embolization (TAE) Alone or combined with Thermal Ablation
NIH Principal Investigator: Bradford Wood, M.D.
Director, Center for Interventional Oncology
Diagnostic Radiology Department (DRD)
National Institutes of Health (NIH)
10 Center Drive, Bldg. 10, Rm 1C341 (MSC 1182)
Bethesda, Maryland 20892-1074
Phone:  301-496-7739
Email:  bwood@nih.gov
Device:  
Device Name:
LC bead LUMI Radiopaque embolic beads
FDA 510(k) Clearance:
K152157
Manufacturer:
BTG

Abbreviated Title:  RFA + TACE with RO Beads
Version Date:  04/13/2018
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PRÉCIS 
Background:

Hepatocellular Carcinoma (HCC) is the 3rd most common cause of cancer globally with 
an increasing incidence worldwide.

Management of hepatic malignancies from primary Hepatocellular Carcinoma (HCC) or 
metastatic disease involves a multidisciplinary approach of surgery and chemotherapy 
and in the case of HCC, transplant, anti-VEGF sorafenib, or local or regional image 
guided therapies. 

Thermal ablation (RFA or MWA) and transarterial embolization (TAE) are minimally 
invasive image guided local or regional therapies that have been extensively studied for 
decades, and more recently and to a lesser extent have been studied together as a 
combination therapy.

LC Bead LUMI™, a radiopaque embolic bead product (company code BTG 13-002), is 
an imageable spherical embolic product that can be visualised by X-ray based imaging 
(e.g., fluoroscopy and CT).  

The beads are non-resorbable microspheres with calibrated size ranges that occlude 
arteries for the purpose of blocking the blood flow to a target tissue. 

LC Bead LUMITM are intended to be used for the embolization of hypervascular tumors 
and arteriovenous malformations (AVMs). 
Objectives:

To determine the imaging characteristics of radiopaque beads including qualitatively 
comparing virtual and actual bead perfusion in the treatment of hepatic tumors using bead 
embolization. 
Eligibility:

Treatment eligibility for TAE requires agreement between the  Interventional Radiologist 
reviewing imaging and feasibility of TAE and the patient's NIH primary treatment team 
who will evaluate the patient's clinical parameters to undergo anesthesia and the TAE and 
or ablation procedure. 

At least ≥18 years of age

Patients with pathologically proven, hepatic-dominant neoplasm.

The extent of hepatic metastases is <50% of total hepatic volume.

Past treatment with Y90 must be 6 months from TAE treatment and liver function within 
NIH institutional limits

ECOG performance status <2 

Patients must have normal organ and marrow function per laboratory parameters

Patients with minor allergies to iodine will also be excluded.
Design:

Number of Participants: 30

Abbreviated Title:  RFA + TACE with RO Beads
Version Date:  04/13/2018
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
Recruitment Time Frame: ~2 years

Type of Study: Feasibility study

This is a pilot study to assess the characteristics of radio-opaque bland beads during TAE 
in the treatment of hepatic malignancies. Patients may also receive thermal ablation 
treatment in conjunction with TAE if clinically indicated, although comparison of bead 
treatment with or without thermal ablation is not part of the study’s aim. 

To compare virtual and actual perfusion characteristics of the LUMI radiopaque beads 
with CBCT and/or CT. Patients’ scans will be obtained per TAE standard of care 
schedule. Other imaging evaluation of this therapy may be performed at regular intervals 
following completion of treatment, and will be governed by standard conventional 
imaging regimen post treatment.  

The choice of which combination of imaging (CT, Cone beam CT (CBCT), or 
fluoroscopy) and when to image, will be made by the clinical care team for the patient, 
based upon multidisciplinary recommendations and NIH Clinical Center customary use 
and standard of care, and will be purely clinical decisions (not research-related).

The participants will have a diagnosed hepatic malignancy, and be eligible to undergo 
transarterial embolization and thermal ablation under general anesthesia.  The LC LUMI 
bead will be used in the transarterial embolization procedure.

Follow up will continue for 12 months from the time of initial treatment. 

Patients will be evaluated in multidisciplinary GI medical oncology clinic and up to 30 
patients will be enrolled to accrue 20 evaluable patients.

Abbreviated Title:  RFA + TACE with RO Beads
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TABLE OF CONTENTS 
PRÉCIS............................................................................................................................................3
TABLE OF CONTENTS ................................................................................................................5
1
INTRODUCTION ...................................................................................................................8
1.1
Study Objectives ...............................................................................................................8
1.1.1
Primary Objective......................................................................................................8
1.2
Background and Rationale................................................................................................8
1.2.1
Virtual Perfusion......................................................................................................10
1.2.2
LC Bead LUMI™....................................................................................................10
1.2.3
Summary and Rationale...........................................................................................10
2
ELIGIBILITY ASSESSMENT AND ENROLLMENT .......................................................11
2.1
screening evaluation........................................................................................................11
2.2
Eligibility Criteria ...........................................................................................................11
2.2.1
Inclusion Criteria .....................................................................................................11
2.2.2
Exclusion Criteria ....................................................................................................11
2.3
Recruitment Strategies ....................................................................................................11
2.4
Registration Procedures ..................................................................................................11
2.5
Pre-operative (Baseline) Evaluation ...............................................................................12
3
STUDY IMPLEMENTATION .............................................................................................12
3.1
Study Design...................................................................................................................12
3.2
Procedure ........................................................................................................................13
3.2.1
Ablation and Embolization Procedure.....................................................................13
3.2.2
Post Ablation and Transarterial Embolization Care ................................................14
3.2.3
Follow up Procedures ..............................................................................................14
3.2.4
Study Stopping Rules ..............................................................................................14
3.3
Study Calendar................................................................................................................15
3.4
Criteria for Removal from Protocol Therapy and Off Study Criteria.............................15
3.4.1
Criteria for removal from protocol therapy .............................................................15
3.4.2
Off-Study Criteria....................................................................................................16
3.4.3
Off Protocol Therapy and Off-Study Procedure......................................................16
4
DATA COLLECTION AND EVALUATION .....................................................................16
4.1
Data Collection ...............................................................................................................16
4.1.1
Baseline Data Collection .........................................................................................17

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4.1.2
On Study Data Collection........................................................................................17
4.1.3
Exclusions to Adverse Event Data Collection.........................................................17
4.1.4
Follow up of Adverse Events ..................................................................................18
4.1.5
Device Records........................................................................................................18
4.1.6
Handling and storage of data and documents..........................................................18
4.1.7
Record Retention .....................................................................................................19
4.2
Data Sharing Plans..........................................................................................................19
4.2.1
Human Data Sharing Plan .......................................................................................19
4.3
Response Criteria ............................................................................................................19
4.3.1
Definitions ...............................................................................................................19
4.4
Toxicity Criteria..............................................................................................................20
5
SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING PLAN
20
5.1
Definitions.......................................................................................................................20
5.1.1
Adverse Event..........................................................................................................20
5.1.2
Adverse Device Effect.............................................................................................21
5.1.3
Serious Adverse Device Effect (SADE)..................................................................21
5.1.4
Unanticipated adverse device effect ........................................................................21
5.1.5
Serious .....................................................................................................................21
5.1.6
Disability..................................................................................................................21
5.1.7
Protocol Deviation (NIH Definition).......................................................................21
5.1.8
Non-compliance (NIH Definition) ..........................................................................21
5.1.9
Unanticipated Problem ............................................................................................21
5.2
NCI-IRB and Clinical Director Reporting......................................................................22
5.2.1
NCI-IRB and Clinical Center CD Expedited Reporting of Unanticipated Problems 
and Deaths .............................................................................................................................22
5.2.2
NCI-IRB Requirements for PI Reporting at Continuing Review............................22
5.3
Expedited Adverse Event Reporting Criteria to the Manufacturer.................................22
5.3.1
Investigator Responsibilities....................................................................................23
5.4
Data and Safety Monitoring Plan....................................................................................23
5.4.1
Principal Investigator/Research Team.....................................................................23
5.4.2
Monitoring Plan.......................................................................................................24
6
STATISTICAL CONSIDERATIONS ..................................................................................24
7
COLLABORATIVE AGREEMENTS..................................................................................25

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7.1
CRADA...........................................................................................................................25
8
HUMAN SUBJECTS PROTECTIONS................................................................................25
8.1
Rationale For Subject Selection......................................................................................25
8.1.1
Selection Based On Gender, Ethnic, Race...............................................................25
8.1.2
Justification for Exclusion .......................................................................................25
8.2
Protection of Patient Rights ............................................................................................25
8.2.1
Confidentiality .........................................................................................................26
8.3
Participation of Children.................................................................................................26
8.4
Participation of Subjects Unable to Give Consent..........................................................26
8.5
Evaluation of Benefits and Risks/Discomforts and Risks/Benefits Analysis.................26
8.6
Consent and Assent Process and Documentation ...........................................................28
8.6.1
Informed consent of non-English speaking subjects ...............................................28
9
DEVICE INFORMATION....................................................................................................29
9.1
LC Bead LUMITM ...........................................................................................................29
9.1.1
Device design and performance specification .........................................................30
9.1.2
Preparation of LC Bead LUMI™............................................................................30
9.1.3
Delivery Instructions ...............................................................................................31
9.1.4
Labeling ...................................................................................................................32
9.1.5
Carton Label ............................................................................................................32
9.1.6
Vial Label ................................................................................................................32
10
REFERENCES ......................................................................................................................33
11
APPENDICES .......................................................................................................................35
11.1
Appendix A: FDA 510 (k) Clearance for LC Bead LUMI .........................................35
11.3
Appendix C: LC Bead LUMI™ Radiopaque Embolic Bead Instructions For Use ....39

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1
INTRODUCTION
1.1
STUDY OBJECTIVES
1.1.1
Primary Objective
To determine the imaging characteristic of radiopaque beads including qualitatively comparing 
virtual and actual bead perfusion in evaluating tumor vascularity in the treatment of hepatic 
tumors using bead embolization.
1.2
BACKGROUND AND RATIONALE
Management of hepatic malignancies from primary Hepatocellular Carcinoma (HCC) or 
metastatic disease involves a multidisciplinary approach of surgery and chemotherapy and in the 
case of HCC, transplant, anti-VEGF sorafenib, or local or regional image guided therapies. The 
less invasive approaches of transarterial embolization (TAE) or ablation with thermal energy 
(radiofrequency or microwave) are options that can be palliative or curative. Each approach has 
its potential for complications that are modest in comparison to surgery. 
Treatment of hepatic malignancies with TAE or ablation alone often requires multiple courses 
because tumor margins are not well delineated by current imaging.  Defining tumor locations 
during the course of an ablation or TAE may enhance accuracy and ability to devascularize the 
tumor and ultimately causing tumor death.  BTG and NIH have collaborated to create a 
radiopaque bead called LC LUMI bead. These are investigational radiopaque, biocompatible, 
non-resorbable beads manufactured to be visible under multiple modes of imaging (fluoroscopy, 
CT, and cone beam CT).  BTG PLC International and its subsidiary UK company, 
Biocompatibles developed the LC Lumi bead under a CRADA with the NIH, and LC Lumi bead 
is manufactured by BTG PLC, an international specialty pharmaceutical company that is 
developing and commercializing products targeting critical care, cancer neurologic and 
interventional medicine. The FDA has granted BTG a 510 (k) Clearance for the LC LUMI beads 
on December 11, 2015 (see Appendix A, Section 12.1)
Hepatocellular Carcinoma (HCC) is the 3rdth most common cause of cancer globally with an 
increasing incidence worldwide [1].  In countries that lack systemic screening for cirrhotic 
patients, 50-70%, are diagnosed with advanced stage, symptomatic HCC [2].  Liver tumors have 
historically responded poorly to systemic chemotherapies and radiation, while < 30% are 
candidates for surgery or transplantation due to inadequate functional liver reserve at advanced 
disease [3].  In recent years, minimally invasive procedures have been shown effective for 
certain patients who do not qualify for surgical resection.  Thermal ablation (RFA or MWA) and 
embolization (TAE) are minimally invasive image guided local or regional therapies that have 
been extensively studied for decades, and more recently and to a lesser extent have been studied 
together as a combination therapy. The use of TAE without chemotherapy (vs. TACE = with 
chemotherapy). Thermal ablation and TAE (or TACE) have been used separately or together as 
acceptable treatments for focal malignancies in the liver [4-7].  Local and regional therapies may 
provide benefits in comparison to traditional cancer treatments, with reduced morbidity and 
mortality, can be performed on an outpatient basis, repeated over time, and used in conjunction 
with other cancer treatments [8].  
Metastatic cancer to the liver is common from primary liver cancer, neuroendocrine tumors, 
colorectal, lung, and urogenital cancers (adrenal, kidney, and bladder) and are treated with 
embolization and or ablation, often with the goal of debulking of palliation.
Commented [WA([1]:  Moved to statistical section as this is 
more of another way to measure the primary objective. Will need 
SRC approval as another primary objective. 

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Thermal ablation and TAE attack different components of the tumor and can work 
synergistically to create an additive effect of treatment, potentially resulting in a more robust 
response. 
Thermal ablation treats the center or “inside” of the tumor, potentially leaving behind a viable 
hypervascular margin sub-lethally treated secondary to the “heat sink effect” [9-11].  This 
hypervascular margin on the “outside” of the tumor is the target of embolization which targets 
and embolizes the vasculature, potentially eliminating this viable margin [12, 13].
RFA and MWA produce tissue death through hyperthermic injury.  Coagulation necrosis occurs 
from an alternating high frequency electric current in the radiofrequency range (460-500 kHz).  
This is delivered via an electrode placed directly in the target lesion and the movement of ions 
within the tissue creates frictional heat as the ions try to follow the alternating current [14].  RFA 
is currently the most common ablative therapy, recommended for lesions ≤3cm (single or up to 3 
lesions) and single lesions ≤5cm who are not candidates for liver resection or liver transplant, but 
have preserved liver function [7]. This results in very narrow indications.  The major limiting 
biological factor to thermal ablation is hepatic blood flow.  The body temperature blood in 
adjacent tumor blood vessels is relatively cooler than the ablation zone, leading to conduction of 
thermal energy away from the target tissue and into the blood.  The result is limited heating of 
perivascular tissue and subsequent irregularly shaped treatment spheres of ablation [10, 15].  
This “heat sink” effect results in sparing of tumor cells nearest the blood vessels, with 
subsequent tumor regrowth.  Given this phenomenon, different methods of hepatic blood flow 
reduction, and direct treatment of perivascular cells with regional chemotherapy have been 
developed, including TACE or DEBs.
MWA uses electromagnetic energy creating a rapid and homogeneous heating of tissue and 
subsequently coagulation necrosis. Another mechanism of MWA function is ionic polarization 
with conversion of kinetic energy into heat. A more homogeneous, larger ablation zone that is 
easily predicted is feasible and the heat- sink effect is attenuated. One reason for the reduced 
heat-sink effect may be the faster heating and higher temperatures provided by microwave 
energy. Notably, the ablation heat beyond the microwave field is conducted in a similar way as 
in RFA with the heat- sink effect still present. Another consequence of the different production of 
heat seen with MWA is that the time needed for ablation is less in MWA than that required in 
RFA.
Transcatheter arterial embolization is a standard treatment option for patients with unresectable 
primary hepatocellular carcinoma (HCC) and is used to treat some liver metastases. Despite the 
widespread use and success of embolization for more than three decades, there remains a lack of 
consensus regarding optimal technique. For example, there is variability in (i) type and size of 
embolic agent, (ii) use of chemotherapeutic agent(s), (iii) degree of catheter selectivity,  and (iv) 
optimal embolization endpoint. This material and technical variability may be perpetuated by a 
lack of knowledge concerning the influence of these embolization variables on patient outcomes. 
Educated recommendations to standardize material choice and procedural technique may be 
formulated if embolic material and drug locations inside the embolized tissue were known with a 
high degree of confidence.
Although extensive experience has been accumulated for both RFA and TACE or DEBs for the 
treatment of a variety of liver tumors, the reoccurrence rates of liver lesions treated with each 
alone have been reported to be quite high, largely depending upon patient selection and size and 

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number of lesions.  Since each treatment attacks the tumor in different ways, it could potentially 
be more effective than either alone.
Studies in the literature have already implemented combination therapy of RFA and TACE or 
DEBs and shown it to be both feasible and safe [1, 16-19].  These studies have thus far shown 
improved progression free survival with tumors ≥ 3cm with combination therapy as compared to 
RFA alone.  They have also shown that overall survival is improved with tumors > 5cm, and that 
combination therapy is comparable to RFA alone along all tumor sizes [16, 18, 20].  Although 
these studies have shown combination therapy to be safe and feasible, there is currently no 
standard convention for how to most effectively combine the two.  Studies have completed 
TACE followed by RFA same day, 1 week or up to 3 to 4 weeks after the initial procedure.  
Other studies have performed RFA followed by TACE.  Coming to a conclusion of overall 
effectiveness from these varying protocols is challenging and more studies are needed to assess a 
standard convention.  
Additionally, subject treated with Y90 at least 6 months prior to treatment and meet all other 
eligibility requirements will be eligible. These subjects were ineligible initially due to concerns 
of Y90 induced hepatic dysfunction and uncertainty of LUMI LC beads additive effects.
1.2.1
Virtual Perfusion
Another factor during treatment of HCC and liver metastases with TAE is the ability to 
accurately determine the vessels for embolization and to effectively perfuse the selected vessels 
with beads during the procedure. Limited tumor vascularity and overlapping vessels can pose a 
challenge in determining the ideal location necessary for embolization with beads. EmboGuide a 
FDA-approved software medical device, will be used to assist the physician performing the 
procedure by having the functionality to analyze tumor vascularity, and the capability to identify 
and annotate the feeding vessels intended for embolization. The software will enable comparison 
for the actual and virtual perfusion characteristics of LUMI beads during embolization. 
1.2.2
LC Bead LUMI™
LC Bead LUMI™, a radiopaque embolic bead product (company code BTG 13-002), is an 
imageable spherical embolic product that can be visualized by X-ray based imaging (e.g., 
fluoroscopy, CBCT, and CT).  The beads are non-resorbable microspheres with calibrated size 
ranges that occlude arteries for the purpose of blocking the blood flow to a target tissue. LC Bead 
LUMITM are intended to be used for the embolization of hypervascular tumors and arteriovenous 
malformations (AVMs). 
1.2.3
Summary and Rationale
LC Bead ™ microspheres are indicated for embolization of hypervascular tumors and have been 
commonly used for embolization of liver tumors. Certain hepatic-dominant hypervascular 
neoplasms may be treated with minimally invasive image guided therapies ablation and 
transarterial embolization. In the past, LC beads were not made visible on x-rays, therefore the 
physician was unable to visualize the exact location of the beads. Lumi beads are basically LC 
beads with iodine, so they can be visualized on x-ray or CT, and show the physician where the 
beads are going. Characterizing the bead appearance on x-ray, fluoroscopy, and CT could inform 
future treatments by identification of tumor at risk for under-treatment, which may also help 
targeting for further treatment (sometimes with RFA), or for follow up. 

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2
ELIGIBILITY ASSESSMENT AND ENROLLMENT 
2.1
ELIGIBILITY CRITERIA
Patients will be screened for this study only after the patient has been determined eligible for the 
TAE procedure by the referring/ primary team and an interventional radiologist. 
2.1.1
Inclusion Criteria
2.1.1.1
Patients who are determined to be eligible for TAE by an interventional radiologist and 
the primary/referring team will be eligible for the study.
2.1.1.2
Patients with pathologically proven hepatic-dominant neoplasm that might otherwise be 
candidates for standard clinical TAE. 
2.1.1.3
Extent of hepatic metastases is <50% of total hepatic volume. 
2.1.1.4
At least ≥18 years of age: Because it is exceeding rare for someone under the age of 18 
to develop hepatocellular carcinoma, we will exclude patients <18 years of age, children 
are excluded from this study, but will be eligible for future pediatric trials.
2.1.1.5
ECOG performance status 0-2 
Six months since last treatment with Y90 
2.1.1.6
Patients must have normal or adequate organ and marrow function as defined below: 
Laboratory tests
Inclusion Criteria
Absolute 
Neutrophil Count
> 1500 / mm3 without help of Filgrastim or other 
stimulating growth factors
Platelet Count
Patient eligible if platelet count is correctable to 
≥50,000/mm3 
Hematology
Hemoglobin
Patient eligible if hemoglobin count is correctable to ≥ 
8.0 g/dl
ALT/AST
≤ 5 times the upper limit of normal; except in the 
presence of obstructive liver metastases where ALT/AST 
may be up to 10 times the upper limit of normal
Creatinine
<1.5x institution upper limit of normal OR
creatinine clearance ≥ 45mL/min/1.73 m2 for patients 
with creatinine levels above institutional normal.
Total Bilirubin
≤ 3 mg/dl
Serum 
Chemistry
Prothrombin Time
within 2 seconds of the upper limit of normal (INR1.8)
2.1.1.7
Ability of subject to understand and the willingness to sign a written informed consent 
document.
2.1.1.8
Evidence of post-menopausal status or negative urinary or serum pregnancy test for 
female pre-menopausal patients. Women will be considered post-menopausal if they 
have been amenorrheic for 12 months without an alternative medical cause. 
2.1.2
Exclusion Criteria
2.1.2.1
No contraindications to receive iodine products.

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2.1.2.2
Main Portal Vein Occlusion or other contraindications to chemoembolization
2.1.2.3
Prior selective internal radiation therapy (SIRT) with 90-Y of more than one treatment 
per lobe or a single whole liver treatment less than 6 months from proposed treatment.
2.1.2.4
Patients taking immunosuppressive drugs or unable to come off of ongoing chronic 
anticoagulation will not be eligible.
2.1.2.5   Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection with systemic manifestations, symptomatic congestive heart failure, unstable 
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would 
limit compliance with study requirements.
2.1.2.6
Pregnant women and nursing mothers are excluded from this study because of the 
potential for teratogenic or abortifacient effects of required multiple imaging and 
associated radiation doses, anesthesia and risks during thermal ablation to the fetus. 
Enrolled patients 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 is 
participating in this study, she should inform her treating physician immediately.
2.1.3
Recruitment Strategies
Potential study candidates may be referred from other NIH clinical studies to treat liver cancer. 
This study is “Enrolling by invitation only”. 
2.2
SCREENING EVALUATION
Patients will be screened and evaluated for ability to undergo the TAE procedure by the referring 
physician or primary team prior to referral to this study. All screening procedures to determine if 
a patient is eligible for the TAE procedure, including but not limited to imaging scans, labwork, 
and pre-anesthesia evaluation, will be performed , ordered, reviewed and documented in the 
electronic medical record (CRIS) by the referring/primary team per routine clinical care. After 
completion of screening evaluation procedures, the primary or referring team and an 
interventional radiologist or his designee will document that the patient is eligible for TAE (and 
thermal ablation, if applicable) and direct enrollment onto this study.
2.2.1
Research Team Screening Responsibilities
Prior to enrollment in this study, the research team will review the following and place a note in 
CRIS of patient’s eligibility:
1) H&P 
2) Imaging – may include CT of the abdomen and pelvis, MRI of the abdomen, MRI/PET or 
CT/PET, and US of the abdomen.
3) Laboratory results
2.3
REGISTRATION PROCEDURES
Authorized staff must register an eligible candidate with NCI Central Registration Office (CRO) 
within 24 hours of signing consent.  A registration Eligibility Checklist from the web site 
(http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) must be completed and sent via 
encrypted email to:  NCI Central Registration Office ncicentralregistration-l@mail.nih.gov.    
Verification of Registration will be forwarded electronically via e-mail to the research team. A 
recorder is available during non-working hours. 
Commented [GC([2]:  Can we delete this? We will need a 
justification for removal.

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2.4
TREATMENT ASSIGNMENT AND RANDOMIZATION/STRATIFICATION PROCEDURES
Cohorts
Number
Name
Description
1
Patients
Patients who have primary or metastatic liver cancer
Arms
Number
Name
Description
1
Experimental
Treatment of hepatic tumors using bead embolization
Randomization and Arm Assignment
Patients in cohort 1 will be directly assigned to arm 1
2.5
PRE-OPERATIVE (BASELINE) EVALUATION

Review of history and physical exam

Review of laboratory results
3
IMAGING STUDIES STUDY IMPLEMENTATION
3.1
STUDY DESIGN 
Screening/Consent/Baseline
Evaluation by the primary or referring team along with a 
radiologist, to determine if patient is eligible for TAE.
Determine eligibility to 16-CC-0049 by reviewing History 
and Physical Exam, Laboratory Results, and Imaging 
Patient signs consent.
 Screening and consent process documentation entered in 
CRIS. 
Treatment*
Admit to NIH CC inpatient ward
Undergo appropriate interventional procedures
CBCT scan pre and after LUMI beads injection to evaluate 
virtual perfusion characteristics.
Inpatient visit post procedure
Imaging may occur before discharge1
Follow up
CT scan and other 
interval scans up to 1 year from initial treatment 
per standard of care
End of Study
History and Physical
ECOG performance score
Laboratory Assessment
Radiology Assessment
Recruitment

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1as clinically indicated
*Patients may require re-treatment
3.2
PROCEDURE 
Patients will be admitted to the NIH inpatient oncology ward and then brought to the 
interventional radiology suite where consent for both procedures and anesthesia using standard 
NIH consents will be obtained. 
Standard transarterial embolization using LC Bead LUMI (Biocompatibles UK Ltd) Radiopaque 
Embolic radiopaque, biocompatible, non-resorbable, hydrogel beads typically with thermal 
ablation (microwave or radiofrequency) in an order appropriate to the clinical picture, will be 
administered in the Interventional Radiology Section under general anesthesia provided by the 
Clinical Center Department of Perioperative Medicine (DPM).  Patients will remain primarily 
under the care of their primary team, typically NCI medical oncology service, or surgical 
oncology service.  
The use of thermal ablation devices (RFA or MWA) and transarterial embolization will be 
according to manufacturer’s instructions and the standard of care at the institution.  Thermal 
ablation treatments will be administered according to the thermal ablation device instructions and 
the Standard of Care of the IR/CC/ NIH.  The choice of which device to use will be at the 
discretion of the physician performing the procedure based on the factors particular to the 
patient’s lesion(s).  TAE will be administered with LC LUMI beads in accordance with the TAE 
device instructions and the Standard of Care of the IR/CC/ NIH and will be administered after an 
ablation treatment.  Retreatment may be done at the recommendation of the physician, according 
to conventional standards.  Multiple lesions may be treated with TAE with LC LUMI beads with 
or without thermal ablation.
3.2.1
Ablation and Embolization Procedure
During this clinical protocol, standard thermal ablation performed with general anesthesia, and 
CT and ultrasound guidance, often to include fusion guidance (“Medical GPS”).  At the NIH, 
thermal ablation will be conducted according to the standard of care and practice guidelines that 
have been in effect for TAE and RFA treatment procedures at the CC since 1998. 
TAE is the most common procedure used to treat HCC.  The process involves cannulating tumor 
nourishing vessels and occluding the blood supply using materials such as beads, that can be 
combined with anti-neoplastic agents or not.  The procedure involves arteriography of the 
superior mesenteric and celiac vasculature to identify a roadmap of vessels and vascular 
anomalies (accessory or replaced hepatic vasculature), confirm portal vein patency, and identify 
hepatic arterial anatomy. This is typically followed by a selective common hepatic arteriography 
to recognize non-target vessels supplying the pancreas, duodenum, or stomach.  Relevant non-
target vessels that cannot be excluded by distal catheter tip positioning may be selectively 
embolized to prevent unintended chemoembolization.  For patients with multifocal disease or 
tumors that span both lobes, embolization of each lobe may be performed in two or more 
separate treatment sessions. The selected hepatic lobar artery (typically right or left) will be 

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14
catheterized for TAE with LC LUMI beads.  An attempt will be made to exclude the cystic artery 
from the embolization distribution.  Extrahepatic branch vessels may be prophylactically 
embolized at the discretion of the Principal Investigator to mitigate the risk of non-target 
deposition of LC LUMI beads.  TAE will continue typically until near-complete flow stasis is 
observed in the target artery (where no non-target reflux of contrast material into more proximal 
branches is observed).  If significant antegrade flow is observed in the target artery following 
procedure, additional embolization using LC LUMI beads may typically be added to reach the 
embolization endpoint.  Visibility of the LC LUMI beads will be recorded using a 3 point scale: 
0, definitely not visible; 1, probably visible; and 2, definitely visible. A CBCT scan may be 
obtained post LUMI beads injection to evaluate virtual perfusion characteristics of the beads for 
predictive investigations of their delivery and function.. The catheter will then typically be 
retracted into the common hepatic artery and completion arteriography will document the degree 
of target vessel flow stasis and non-target vessel patency.
Thermal ablation therapy may be administered based on the clinical evaluation of the patient and 
when appropriate will be done according to the manufacturer’s instructions for use.  After 
infiltration of the skin (for percutaneous approach) with a local anesthetic, the needle of the 
chosen system will be directed into the lesion, with image guidance and the needle is confirmed 
to be in the lesion by imaging.  After confirming appropriate positioning, the lesion will be 
heated typically for 10-15 minutes, according to manufacturer’s guidelines.  The exposure time 
may be varied depending on the temperatures achieved and proximity of adjacent anatomy or 
other patient-specific anatomy or issues.  Depending on the size of the lesion to be ablated, 
multiple locations of the needle as well as multiple ablation cycles will be performed in order to 
ideally achieve an approximately 1-cm margin of ablated tissue around the lesion or target 
volume.  Adequacy of ablation will be followed by ultrasound throughout the procedure, when 
possible.  Depending on the size of the lesions and the time required to complete the ablation, 
multiple lesions may be treated, often as staged procedures.
3.2.2
Post Ablation and Transarterial Embolization Care
During hospitalization, the patients will be admitted to the patient care unit following 
interventional procedures for routine post-procedure monitoring and inpatient care.  Antibiotics, 
anti-emetics, hydration and comfort medicines will be administered based on the patient’s 
clinical status.  Laboratory study including a CBC, hepatic panel (alkaline phosphatase, bilirubin, 
AST and ALT), acute care (Na, K, CL, CO2, BUN, Cr), and Mineral panel (Mg, albumin, Phos, 
Ca,) will be typically obtained upon admission and daily post procedure, while in the hospital, 
according to standard clinical practice.  Immediate imaging may occur if clinically indicated, 
based on the patient’s clinical status and at the PI’s discretion, as is standard of practice.  Length 
of stay will be based on clinical status of the participant and the discretion of the PI 
3.2.3
Follow up Procedures
Subsequent Clinical Center visits following treatment for study participants will be determined in 
accordance with the participants’ primary medical or surgical oncology team and in collaboration 
with the study PI, as clinically indicated.  
Imaging and laboratory assessments will be typically repeated as clinically warranted during 
the12 months after initial treatment, or at least until evidence of disease remission, stabilization 
or recurrence or residual disease is documented. A CT scan will be obtained within 2 months 
post treatment to evaluate virtual perfusion characteristics of the LUMI beads. 

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3.2.4
Study Stopping Rules
Enrollment will be halted and the IRB notified if:

Three or more patients with a non-laboratory grade 4 toxicity within the first 72 hours 
post TAE whether or not considered TAE or research-related.

Death due to any cause within the first 72 hours post TAE.
All patients will be monitored until there is improvement or resolution of toxicity. Once the IRB, 
has completed their review; they must give their permission for the study to resume.

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3.3
TYPICAL STUDY CALENDAR*
a CT/ CBCT, MRI, or PET scan. All radiological imaging to be performed as clinically indicated and 
based on the status of the patient.
b Off treatment is 72 hours post TAE.
c Patient may require repeat procedures
d See section 4.1.4 for AE data collection and management during the follow up period.
* Primary teams determine course of follow up, but usually request treating Interventional Radiologist 
input.
Treatment
Post Treatment
Follow up
Procedure
Screening
Pre-operative evaluation prior to 
receiving LUMI beads treatment 
Day 0 to 
discharge 
or until 
off 
treatmentb
Within 2 
months post 
treatment
Any time 
point up to 
12 months 
from initial 
treatment
Procedures performed by the Referring/ Primary Team
Evaluation to determine if patient is eligible for 
TAE
X
H&P to include baseline symptoms, concomitant 
medications, etc.
X
Labs 
X
Procedures performed by the Research Study Team
Consent
X
Review of Radiological Assessments a 
X
X
X
X
X
Review of H&P, labs, and concomitant meds
  X
TAE (if appropriate may include thermal 
ablation)
X
Xc
Xc
Response Evaluation
X
X
X
Adverse Events
X
Xd
Xd

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3.4
CRITERIA FOR REMOVAL FROM PROTOCOL THERAPY AND OFF STUDY CRITERIA
3.4.1
Criteria for removal from protocol therapy

Toxicity that prevents further imaging (e.g., renal dysfunction as serum creatinine 
>2.0mg/dl and precludes CT or MRI imaging)

Patients will be considered “off treatment” 72 hours following TAE

Participant requests to be withdrawn from active therapy

Unacceptable Toxicity as defined in section 3.2.4

Investigator discretion
3.4.2
Off-Study Criteria

Inability to complete a single session of TAE  

Completed 12-month follow-up period

Participant requests to be withdrawn from study

Loss of capacity to provide informed consent

Death

Patient becomes eligible for hepatic surgical resection, transplant, or other treatment.
Eligible candidates who have signed the consent and become unable to undergo treatment (due to 
rapid progression of diseases, etc.) will come off the study. CRO will be notified of the off study 
reason. 
3.4.3
Off Protocol Therapy and Off-Study Procedure
Authorized staff must notify Central Registration Office (CRO) when a subject is taken off 
protocol therapy and when a subject is taken off-study.  A Participant Status Updates Form from 
the web site (http://home.ccr.cancer.gov/intra/eligibility/welcome.htm) main page must be 
completed and sent via encrypted email to:  NCI Central Registration Office 
ncicentralregistration-l@mail.nih.gov.
4
DATA COLLECTION AND EVALUATION 
4.1
DATA COLLECTION
All data will be kept secure. The PI will be responsible for overseeing entry of data into an in-
house password protected electronic system and ensuring data accuracy, consistency and 
timeliness. The principal investigator, associate investigators/research nurses and/or a contracted 
data manager will assist with the data management efforts. All human subjects personally 
identifiable information (PII) as defined in accordance to the Health Insurance Portability and 
Accountability Act, eligibility and consent verification will be recorded. Primary data obtained 
during the conduct of the protocol will be kept in secure network drives or in approved 
alternative sites that comply with NIH security standards. Primary and final analyzed data will 
have identifiers so that research data can be attributed to an individual human subject participant.
All AEs, including clinically significant abnormal findings on laboratory evaluations, regardless 
of severity, will be followed for 30 days or until return to baseline or stabilization of event. 

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Serious adverse events that occur more than 30 days after the last administration of 
investigational agent/intervention and have an attribution of at least possibly related to the 
agent/intervention should be recorded and reported.
An abnormal laboratory value will be considered an AE if the laboratory abnormality is 
characterized by any of the following:

Results in discontinuation from the study

Is associated with clinical signs or symptoms 

Requires treatment or any other therapeutic intervention

Is associated with death or another serious adverse event, including hospitalization. 

Is judged by the Investigator to be of significant clinical impact

If any abnormal laboratory result is considered clinically significant, the investigator will 
provide details about the action taken with respect to the test drug and about the patient’s 
outcome.
End of study procedures: Data will be stored according to HHS and FDA regulations, and NIH 
Intramural Records Retention Schedule as applicable. 
Loss or destruction of data: Should we become aware that a major breach in our plan to protect 
subject confidentiality and trial data has occurred, the IRB will be notified. 
4.1.1
Baseline Data Collection
Following consent, participating patients will typically undergo a CT of the chest abdomen, and 
pelvis, as clinically warranted. Additional imaging may be obtained if clinically indicated by the 
treating interventional radiologist, to identify the target area. Previous imaging may also be used 
as baseline scans if they fall within the allowed protocol timeframe. Standard baseline 
information which typically includes demographics, disease history, and previous therapy for 
liver malignancies will be collected. 
4.1.2
On Study Data Collection
We will also document bead visibility data during embolization. This information will be 
collected using a qualitative particle visibility scale by applying a 3-point scale: 0, definitely not 
visible; 1, probably visible; and 2, definitely visible [21].
Intra-procedural, post treatment, and follow up images will all be saved and stored in PACS. 
Patient images will be anonymized prior to transfer to a secure work station for analysis.  CRF’s 
and non-image data will be stored in the DRD shared drive which has limited access. The DRD 
shared drive is backed up and managed by the NIH DCRI in keeping with the protection and 
confidentiality guideline of the Privacy Act of 1974.
Any grade 3 events and higher occurring up to 72 hours post treatment (either with combined 
RFA and TAE or with TAE alone) will be collected and recorded in the study database as 
adverse events, except those listed in the Exclusions to Adverse Event Data Collection section 
(see Section 4.1.3). Grade 2 events will be collected and recorded if not resolved before the 
patient is considered off treatment (72 hours post treatment). Grade 1 events will not be collected 
or reported.

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4.1.3
Exclusions to Adverse Event Data Collection
The following adverse events are expected events from the procedure and study device and will 
not be collected unless the nature, severity, and frequency are deemed by the PI as unexpected 
for this patient population. 
Anticipated adverse events related to TAE:

Fever 

Right upper quadrant pain

Acute cholecystitis

Acute pancreatitis or elevation of amylase and lipase

Nausea 

Vomiting

Fatigue

Elevated white blood cell count

Elevated liver enzymes

Bleeding

Groin hematoma

Arterial dissection

Portal vein thrombosis 

Pleural effusions

Aspiration pneumonia from intubation 

Anticipated adverse events related to ablation procedure:*

Pain at the site of ablation needle insertion

Muscle ache

Fever

Fatigue

Nausea

Vomiting

Elevated liver function tests

Hyponatremia following hydro-dissection

Thrombocytopenia and anemia post-RFA

Pleural effusions

Aspiration pneumonia from intubation 

Bleeding
*If ablation is given
Anticipated adverse events related to LC LUMI beads (will collect if grade 3 or above):

Allergic reaction to LC LUMI beads

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4.1.4
Follow up of Adverse Events
All adverse events will be followed until they have abated, or until a stable situation has been 
reached. Depending on the event, follow up may require additional tests or medical procedures 
as indicated, and / or referral to the general physician or medical specialist.
The investigator will evaluate reported adverse events for determination of seriousness and 
causal relationship with the treatment or the device.
4.1.5
Device Records
Records or receipt, use, and disposition of the LC Lumi Radiopaque Embolic beads will be kept 
according to 21CFR 812.140 (a). 

The size, batch number, and expiration date will be recorded for each patient. 

The name of the person who received and used the beads will be documented. Disposal 
of beads, if unused, will also be recorded as well as the person’s name who handled the 
disposal.

Any bead deficiency will also be recorded along with the correspondence with the 
manufacturer.
4.1.6
Handling and storage of data and documents
All individual patient data and records will be collected and maintained on confidential basis and 
according to the applicable national data protection, privacy, and security laws. Data collected 
from subjects enrolled in this protocol may be used in submissions to regulatory agencies, and 
for publications. Summaries of data and information from each patient data form may be used for 
statistical analysis of the investigation’s finding during trial. 
Trial data will be recorded in a database during the trial. Each patient will receive a unique study 
ID. The study investigator shall safeguard a list linking subject names to their ID numbers. 
Access to the database is restricted to personnel involved in conducting the trial. Final trial data 
for the report is expected to be in the database within 3 months from completing the last patient’s 
follow-up.
The study investigator will also be responsible for maintaining all correspondence pertaining to 
the investigation. All shipment, receipt, and disposition of the study device will be kept in the 
electronic regulatory binder. Also kept in the regulatory binder are signed investigator 
agreements, study investigators’ OSHRP training certificates, and COI records.
4.1.7
Record Retention
The investigator will retain the specified records and reports for up to 2 years after the marketing 
application is approved for the investigational device.
4.2
DATA SHARING PLANS
4.2.1
Human Data Sharing Plan
What data will be shared?
I will share human data generated in this research for future research as follows:
 X   De-identified data in BTRIS (automatic for activities in the Clinical Center)
 X   De-identified or identified data with approved outside collaborators under appropriate 
agreements.

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How and where will the data be shared? 
Data will be shared through:
 X   An NIH-funded or approved public repository.  Insert name or names: clinicaltrials.gov.
 X   BTRIS (automatic for activities in the Clinical Center)
 X   Approved outside collaborators under appropriate individual agreements.
 X   Publication and/or public presentations.
When will the data be shared?
 X   Before publication.
 X   At the time of publication or shortly thereafter.
4.3
RESPONSE CRITERIA
4.3.1
Definitions

Evaluable for bead visibility: All patient imaging will be evaluated for the visibility of the 
LC LUMI beads using a 3 point scale: 0, definitely not visible; 1, probably visible; and 2, 
definitely visible as defined the treating interventional radiologists. Other characteristics 
may be noted such as the radiopacity of the beads, visibility of the beads in the tumor, 
overall location of beads in relation to the tumor or targeted site.

Evaluable for toxicity:  All patients will be evaluable for toxicity from the time of their 
treatment with LC LUMI radiopaque beads up to 72 hours post completion of treatment. 
Grade 3 or greater adverse events, including allergic reactions, collected during this time 
period, will be followed until resolution. Expected or anticipated adverse events from the 
research or the study device will not be collected. See Section 4.1.3 for details. 

Evaluable for imaging characteristics: Only those patients who are eligible for the study, 
have received at least one treatment of TAE, and have had their disease re-evaluated per 
standard of care imaging will be considered evaluable.
4.4
TOXICITY CRITERIA
The following adverse event management guidelines are intended to ensure the safety of each 
patient while on the study.  The descriptions and grading scales found in the revised NCI 
Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE 
reporting.  All appropriate treatment areas should have access to a copy of the CTCAE version 
4.0.  A copy of the CTCAE version 4.0 can be downloaded from the CTEP web site 
(http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm#ctc_40). 
5
SAFETY REPORTING REQUIREMENTS/DATA AND SAFETY MONITORING 
PLAN
5.1
DEFINITIONS
Adverse events and serious adverse events are defined for this study following the standard ISO 
14155:2011 for Good Clinical Practice in clinical investigation of medical devices for human 
subjects.

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5.1.1
Adverse Event
Any untoward medical occurrence in a human subject, including any abnormal sign (for 
example, abnormal physical exam or laboratory finding), symptom, or disease, temporally 
associated with the subject’s participation in research, whether or not considered related to the 
subject’s participation in the research. 
5.1.2
Adverse Device Effect
An adverse device effect (ADE) is an AE related to the use of the LC Lumi Radiopaque embolic 
beads.
Serious Adverse Event (SAE) is an AE that results in the following: 

death

serious deterioration of the subject’s health, leading to
o
life-threatening illness or injury, or
o
permanent impairment of a body structure or function, or
o
in-patient or prolonged hospitalization, or
o
medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment of a body structure or function

fetal distress, fetal death or a congenital abnormality or birth defect
5.1.3
Serious Adverse Device Effect (SADE)
A serious adverse device effect (SADE) is an ADE that results in any of the consequences 
characteristic of an SAE. An unanticipated SADE (USADE) is a SADE which is not anticipated 
by the risk analysis, while an anticipated SADE (ASADE) is a SADE which is anticipated by the 
risk analysis.
5.1.4
Unanticipated adverse device effect
Defined as any serious adverse effect on health or safety or any life-threatening problem or 
death caused by, or associated with, a device, if that effect, problem, or death was not previously 
identified in nature, severity, or degree of incidence in the investigational plan or IDE application 
(including a supplementary plan or application), other unanticipated serious problem associated 
with a device that relates to the rights, safety and welfare of subjects.
5.1.5
Serious 
An Unanticipated Problem or Protocol Deviation is serious if it meets the definition of a Serious 
Adverse Event or if it compromises the safety, welfare or rights of subjects or others.
5.1.6
Disability
A substantial disruption of a person’s ability to conduct normal life functions.  
5.1.7
Protocol Deviation (NIH Definition)
Any change, divergence, or departure from the IRB-approved research protocol.  
5.1.8
Non-compliance (NIH Definition)
The failure to comply with applicable NIH Human Research Protections Program (HRPP) 
policies, IRB requirements, or regulatory requirements for the protection of human research 
subjects.

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5.1.9
Unanticipated Problem
Any incident, experience, or outcome that:

 Is unexpected in terms of nature, severity, or frequency in relation to 
(a) the research risks that are described in the IRB-approved research protocol and 
informed consent document; Investigator’s Brochure or other study documents, and
(b) the characteristics of the subject population being studied; AND

Is related or possibly related to participation in the research; AND

Suggests that the research places subjects or others at a greater risk of harm (including 
physical, psychological, economic, or social harm) than was previously known or 
recognized.
5.2
NCI-IRB AND CLINICAL DIRECTOR REPORTING
5.2.1
NCI-IRB and Clinical Center CD Expedited Reporting of Unanticipated Problems and 
Deaths
The Protocol PI will report to the NCI-IRB and CC Clinical Director:

All deaths, except deaths due to progressive disease 

All Serious Protocol Deviations

All Unanticipated Problems

All serious non-compliance
Reports must be received within 7 days of PI awareness via iRIS.
5.2.2
NCI-IRB Requirements for PI Reporting at Continuing Review
The protocol PI will report to the NCI-IRB: 
1. A summary of all protocol deviations in a tabular format to include the date the deviation 
occurred, a brief description of the deviation and any corrective action.
2. A summary of any instances of non-compliance
3. A tabular summary of the following adverse events:

All Grade 2 unexpected events that are possibly, probably or definitely related to the 
research; 

All Grade 3 and 4 events that are possibly, probably or definitely related to the 
research; 

All Grade 5 events regardless of attribution; 

All Serious Events regardless of attribution. 
NOTE: Grade 1 events are not required to be reported. 
5.3
EXPEDITED ADVERSE EVENT REPORTING CRITERIA TO THE MANUFACTURER
The manufacturer will be responsible for all safety reporting related to the use of LC LUMI 
beads. 
The Investigator shall, in accordance with all Applicable Laws and regulations, report all and any 
unanticipated serious adverse events and/or device malfunctions that are at least possibly related 
to the investigational device and/or the investigation to Company within twenty four (24) hours 

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of such  adverse events and/or device malfunctions occurring, and to the relevant authority or 
authorities as shall be required by all such Applicable Laws and regulations (guidance to which 
may be provided in the Protocol).  Investigator shall also provide Company with any other 
information and assistance as may be requested and/or required by Company to allow Company 
to comply with its reporting obligations.
All adverse event data will be forwarded to pharmacovigilance@btgplc.com
5.3.1
Investigator Responsibilities
The Investigator will conduct the study in accordance of the investigational plan, any IRB-
imposed conditions, and applicable FDA regulations for protecting the rights, safety and 
welfare of subjects under the investigator’s care, and for obtaining informed consent from each 
research participant prior to any study related procedures. Investigators are also responsible for 
maintaining control of the investigational device. The Investigator will also assure monitoring 
is conducted according to the monitoring plan. IRB approval of the study must be obtained 
prior to study start and this documentation will be on file. The Investigator will promptly notify 
the IRB of any significant new information about this investigation.
This clinical study is being conducted at Clinical Center National Institutes of Health. 
Investigators may determine if potential subjects would be interested in taking part in the 
investigation but written informed consent will not be obtained from study participants and study 
participation will not be allowed prior to IRB approval.
The investigational device will only be used on research subjects with the investigator’s 
supervision and will not be used on any person who is not authorized under 21CFR812 to 
receive it.
5.4
DATA AND SAFETY MONITORING PLAN
5.4.1
Principal Investigator/Research Team 
The clinical research team will meet on a routine basis when patients are being actively treated 
on the trial to discuss each patient. Decisions about ongoing enrollment and intervention will be 
made based on the toxicity data from prior patients. 
All data will be collected in a timely manner and reviewed by the principal investigator or a lead 
associate investigator. Adverse events will be reported as required above. Any safety concerns, 
new information that might affect either the ethical and or scientific conduct of the trial, or 
protocol deviations/reportable events will be immediately reported to the IRB using iRIS. 
The principal investigator will review adverse event and response data on each patient to ensure 
safety and data accuracy. The principal investigator will personally conduct or supervise the 
investigation and provide appropriate delegation of responsibilities to other members of the 
research staff. 
5.4.2
Monitoring Plan
Accrual and safety data will be monitored by the principal investigator, who will provide 
oversight to the conduct of this study. The PI will continuously evaluate implementation of the 
protocol for any unusual or unpredicted complications that occur and will review the data for 
accuracy and completeness.

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6.0 QUALITY ASSURANCE
The NIH Clinical Center’s quality assurance program will conduct study monitoring at least 
annually or more frequently as required. Patient consent documents, primary outcome and safety 
laboratory results and diagnostic test results will be monitored for accuracy, correct dating, and 
agreement between case report forms and source documents. All regulatory reports, reviews and 
amendments, adverse events, problem reports related to study, the investigator credentials, 
training records, and the delegation of responsibility log will be reviewed during monitoring 
visits. Any major findings will be summarized in writing and reported to the study pi who will be 
responsible for submitting the monitoring report to the IRB.
7.0 STATISTICAL CONSIDERATIONS
 
This is a proof of concept/feasibility study with a small number of evaluable patients and data 
points. Data collected will not be sufficient to provide meaningful statistical analysis.
Sample size was derived from historical experience with pilot feasibility observational studies, 
where a population of 20-30 evaluable patients should provide initial information to begin to 
characterize the imaging features of the approach, which is the main goal. This should allow for 
adequate slight variations in dosages and anatomy to inform such a pilot study. The precise 
characterization of the imaging features will require a much larger future study, but this pilot 
study outcomes and imaging features could be used to power future studies, depending upon the 
primary aims.  No statistical analysis is required to power this trial, as it is a pilot feasibility 
study, and the outcomes related to imaging features will not be statistically analyzed, other than 
simple descriptive statistics. Descriptive statistics will be provided in summary tables.

Categorical variables will be summarised using frequency distribution: number of 
observations (N) and percentages (%). 

Continuous variables will be summarized using standard quantitative statistics: 
o
number of observations (N), 
o
mean, standard deviation (STD), 
o
median and 
o
range (minimum and maximum observed values).
When relevant, the 95% confidence intervals (CI) will also be displayed.
For instance, qualitative analyses may be done to compare virtual and actual perfusion 
characteristics (such as overlap) of LUMI beads using CBCT before, during, and after LUMI 
beads injection.  
If fewer than 20 evaluable patients are enrolled, then the variety of imaging features seen may be 
limited.  Using fewer than 20 evaluable patients could start to substantially compromise the 
ability of the study to provide the necessary rationale for further work in refining and developing 
the clinical use of this approach. Since the emphasis is that this is a PILOT study, this 
recommended study size of N=20 EVALUABLE patients seem to be a good compromise.
Lastly, assuming that possibly up to 33% of recruited patients may turn out to either be ineligible 
or that their data will be inevaluable, a total of N=30 patients will need to be recruited to ensure 
having (roughly) 20 evaluable patients.  If a patient’s follow-up imaging is not available but their 
procedural data is adequate they will be considered evaluable.  Inevaluable patients are defined 

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as patients whose data cannot be reliably recorded in terms that satisfy the primary endpoint. 
This could occur if the data cannot be graded in terms of visibility due to technical issues such as 
patient motion or small doses of beads used in a small volume of tissue.  
8
COLLABORATIVE AGREEMENTS 
8.1
CRADA
The investigational study device is provided by another party under a Collaborative Agreement 
[Cooperative Research and Development Agreement (CRADA) with BTG/Biocompatibles UK 
Limited (#08-02412).
9
HUMAN SUBJECTS PROTECTIONS 
9.1
RATIONALE FOR SUBJECT SELECTION
This study intends to enroll 30 participants who have primary or metastatic liver cancer. The 
study seeks to enroll both women and men who meet eligibility criteria including whites, non-
whites and minorities. Patients who may be unable to comprehend the study requirements and 
associated risks may not be able to be enrolled. The intent of this study is a proof of concept 
safety and feasibility study and as such, children would not be the appropriate patient population. 
9.1.1
Selection Based On Gender, Ethnic, Race
Subjects from both genders and all racial/ethnic groups are eligible for this study if they meet the 
eligibility criteria. Efforts will be made to extend accrual to a representative population. 
Statistical analysis to explore ethnic, race and gender differences will not be performed, as this 
study is not powered to explore any such differences.
9.1.2
Justification for Exclusion
Patients that are pregnant will be excluded from this trial because of concern that ionizing 
radiation may be harmful to the developing fetus. Patients with altered mental status that 
prevents consent or answering questions will be excluded. Patients with uncorrectable 
coagulopathies may be at increased risk for bleeding, and will be excluded. Patients with 
multiple co-morbidities, sepsis, or multiple high-risk medical problems may be at increased risk 
for morbidities or mortalities, and will be excluded. This does not change standard transarterial 
embolization exclusions.
9.2
PROTECTION OF PATIENT RIGHTS
The Radiology and Imaging Sciences Department is responsible for protecting all subjects 
involved in human experimentation. This is accomplished through the IRB mechanism and the 
process of informed consent. The IRB reviews all proposed studies involving human 
experimentation and ensures that the patient’s rights and welfare are protected and that the 
potential benefits and/or the importance of the knowledge to be gained outweigh the risks to the 
individual. The IRB also reviews the Informed Consent document associated with each study in 
order to ensure that the consent document accurately and clearly communicates the nature of the 
research to be done and its associated risks and benefits. The IRB must give full board approval 
of the protocol and consent documents before the study may begin at a site.
9.2.1
Confidentiality
The Radiology and Imaging Sciences Department is responsible for the confidentiality of the 
data associated with patients registered/randomized in this study in the same manner it is 

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responsible for the confidentiality of any patient data within its sphere of responsibility. For 
patients registered/randomized to this study, there are additional considerations related to the 
necessity of sharing of research data with the ACOSOG-CC and representatives of NCI and 
OHRP.
9.3
PARTICIPATION OF CHILDREN
Children will not be eligible for this study.
9.4
PARTICIPATION OF SUBJECTS UNABLE TO GIVE CONSENT
Adults unable to give consent are excluded from enrolling in the protocol. However, re-consent 
may be necessary and there is a possibility, though unlikely, that subjects could become 
decisionally impaired. In these cases, the subject will be taken off study.  
9.5
EVALUATION OF BENEFITS AND RISKS/DISCOMFORTS AND RISKS/BENEFITS ANALYSIS
The risks inherent to this device itself should be identical to the risks of undergoing the clinically 
indicated procedure, and are outlined in detail below. This use of beads for embolization has 
been standard therapy for liver tumors for decades.  The LUMI bead is very similar in 
composition to the widely used over the last decade and commercially available LC bead™.  The 
LUMI LC bead is basically an LC bead with attached iodine to make it visible on x-rays, like 
regular iodine contrast.   The risks of these LUMI LC beads are discussed in the table below:  
No
Potential 
Hazard
Resultant Harm
Risk Evaluation
Discussion
Mitigation
Strategy
1 
Transarterial 
embolization 
Thermal 
ablation
Pain
Bleeding
Infection
Nausea
Anesthesia 
complications
Pneumothorax
Liver abscess 
formation
Acute cholecystitis
Gastric ulceration
Pancreatitis
Misembolization
Radiation Injury
Allergic reactions 
to anesthesia 
medications
Allergic reaction to 
intravenous 
contrast
Liver failure
Stomach ulcer
Postembolization 
syndrome (24-72 
hours following 
chemoembolization
, during hospital 
The LC beads will be 
placed using standard 
of care transarterial 
embolization protocol. 
The tumor site is 
accessed via an 
inguinal artery 
Pre-operative clearance from 
the anesthesia service.
Pain and Palliative care consult 
as clinically indicated
Evaluation of any outstanding 
cardiology, pulmonology or 
other co-morbid disease states 
before IR procedures; routine 
general sedation and peri-
operative, antiemetics, antacids, 
antibiotics, local anesthesia and 
post operative patient 
controlled analgesia, bedrest, 
nursing surveillance and 
antibiotics. 
Patients with known contrast 
allergies will be pretreated per 
standard of care
Patient with known allergies to 
any anesthesia agents will 
receive comparable anesthesia 
medications that they can 
tolerate
Peri-procedure imaging to 
evaluate immediate LC bead 
placement enhanced by the 
beads radiopaque element will 
allow immediate visualization 

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No
Potential 
Hazard
Resultant Harm
Risk Evaluation
Discussion
Mitigation
Strategy
observation 
period)
Abdominal visceral 
injury (from non-
target 
embolization, 1-2 
weeks following 
embolization):
of misembolization.
Patient are admitted to the 
inpatient hospital ward during 
the immediate post-operative 
period and monitored.
Post-operative changes in 
patient comfort vital signs or 
diagnostics such as liver 
enzymes will prompt further 
evaluation.
2
LC Lumi beads
Allergic Response
The preclinical 
experience does not 
raise concerns that the 
radiopaque LC beads 
produces any known 
acute allergic response 
(see Investigator’s 
Brochure).
Patient with known allergy to 
LC beads or its components will 
be excluded from the study
3
LC Lumi beads
Endotoxin adverse 
reaction
The preclinical 
experience does not 
raise concerns that the 
radiopaque LC beads 
produces any known 
acute endotoxin 
response (see  
Investigator’s 
Brochure).
Labeled non-pyogenic
Endotoxin testing in animal 
models proved no change in 
temperature during an 
observation period following 
injection of extracted LC bead 
LUMI.
Acutely febrile patients will be 
excluded from the procedure as 
is standard of care
4
LC Bead 
LUMITM Bead
Genotoxicity, 
Carcinogenicity, 
reproductive toxicity
The preclinical 
experience does not 
raise concerns that the 
radiopaque LC beads 
produces any known 
genotoxicity, 
carcinogenotoxic or 
reproductive toxic 
adverse events (see 
Appendix C, Section 0)
Patients who are of 
reproductive age will be 
counseled on use of adequate 
birth control. All women who 
are of reproductive age and are 
not sterile or post-menopausal 
will be tested for pregnancy 
prior to all imaging.
5
LC Bead 
LUMITM 
beads
Systemic or local 
toxicity
The preclinical 
experience does not 
raise concerns that the 
radiopaque LC beads 
produces any known 
acute systemic or local 
adverse response (see 
Appendix C,  Section 0)
Patient are admitted to the 
inpatient hospital ward during 
the immediate post-operative 
period and monitored. Post-
operative changes in patient 
comfort, physical exam, vital 
signs or diagnostics such as 
liver enzymes will prompt 
further evaluation with imaging 
and immediate treatment.

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9.6
CONSENT AND ASSENT PROCESS AND DOCUMENTATION
All patients who are being considered for this trial will undergo informed consent prior to being 
enrolled in the trial, as well as evaluation by multi-disciplinary review. 
During the initial consultation, the patient, along with family members, is presented a forthright 
and detailed overview of the treatment options available to them at the NIH.  The experimental 
nature of the treatment, its theoretical advantages and disadvantages, and an overview of the 
procedure and anticipated convalescence are presented. The Informed Consent document is 
given to the patient and they are asked to review it, make notes and follow-up with a phone call 
to the physician or nurse investigator to have any additional questions answered prior to 
considering treatment on protocol.
When the patient is admitted to the Clinical Center for treatment, the PI, AI or designee, such as 
the medical staff fellow, will perform the consenting process.
The Investigator will obtain written informed consent from each patient, or their authorized 
representative, participating in the study.   The informed consent form will contain all the 
Essential Elements of Informed Consent set forth in 21CFR, Part 50, the ICH Guideline for 
Good Clinical Practice, and the terms of the Declaration of Helsinki.  Copies of the signed 
document should be given to the patient and filed in the Investigator’s study file, as well as the 
patient’s medical record if in conformance with Standard Operating Procedures. 
9.6.1
Informed consent of non-English speaking subjects
If there is an unexpected enrollment of a research participant for whom there is no translated 
extant IRB approved consent document, the principal investigator and/or those authorized to 
obtain informed consent will use the Short Form Oral Consent Process as described in MAS 
Policy M77-2, OHSRP SOP 12, and 45 CFR 46.117 (b) (2).  The summary that will be used is 
the English version of the extant IRB approved consent document.  Signed copies of both the 
English version of the consent and the translated short form will be given to the subject or their 
legally authorized representative and the signed original will be filed in the medical record.
Unless the PI is fluent in the prospective subject’s language, an interpreter will be present to 
facilitate the conversation (using either the long translated form or the short form). Preferably 
someone who is independent of the subject (i.e., not a family member) will assist in presenting 
information and obtaining consent. Whenever possible, interpreters will be provided copies of 
the relevant consent documents well before the consent conversation with the subject (24 to 48 
hours if possible). 
We request prospective IRB approval of the use of the short form process for non-English 
speaking subjects and will notify the IRB at the time of continuing review of the frequency of the 
use of the Short Form.
10 DEVICE INFORMATION  
10.1 LC BEAD LUMITM
(Also refer to the Investigational Brochure and the LUMI™ Bead Technical Dossier for 
complete information)
LC Bead LUMITM consist of a macromer derived from a sulphonate modified polyvinyl alcohol 
(PVA) macromer and a sulphonated cross-linking agent (AMPS = 2-Acrylamido-2-
methylpropane sulphonate, sodium salt), which contains a radiopaque moiety (triiodobenzyl 

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entity) that is covalently bound within the hydrogel structure. The radiopaque moiety is derived 
from triiodobenzyl aldehyde. The incorporation of this radiopaque moiety into the co-polymer 
imparts X-ray imageability by rendering the beads radiopaque.
Multiple sizes are available for the product LC Bead LUMITM. Glass vials in all size ranges will 
contain approximately 2ml of product in around 6 – 7 ml physiological buffered saline. The total 
volume in the vial is 8 - 9 ml. Each vial is provided sterile (SAL 10-6) via moist heat sterilization 
and is only intended for single use. 
The product is mixed with non-ionic contrast agent, such as OmnipaqueTM (not included with the 
product) to help the physician / radiologist to evaluate the human vascular supply and in order to 
monitor the delivery of the product during the embolization procedure. LC Bead LUMITM will be 
delivered using a typical microcatheter commercially available to the Interventional Radiologist 
community in 2.4 to 4 Fr (French size) ranges. The physician will use the product to administer 
the beads intra-arterially in order to physically block the target vessel.
LC Bead LUMITM has been designed as a radiopaque version of the LC BeadTM. Currently 
embolization with LC Bead TM lacks post-procedural imaging feedback on exact bead location. 
The embolization process with LC BeadTM is monitored by detecting changes in antegrade flow 
of soluble iodinated contrast in which the beads are diluted. The embolization is continued until a 
desired embolization endpoint is reached. This process is completed without specific feedback 
on the bead location. In order to address this limitation, BTG has developed an imageable 
spherical embolic bead that can be visualized by X-ray based imaging (e.g., fluoroscopy and 
CT). The potential benefits envisaged for such a line extension are listed below:

The radiopaque product will embolize the tumor feeding vessels, providing a marker for 
the location of the tumor.

Areas of undertreatment may be detected and this may support the effective planning of 
additional interventions.

The product may facilitate the follow-up of treated tumors by identifying previously 
treated regions. 

The introduction of imageability should allow physicians to identify areas of any 
undesirable non-target embolization. 
10.1.1 Device design and performance specification
LC Bead LUMITM has been designed to allow visualization of the bead product within the blood 
vessel by X-ray based imaging. The design control process considered the design inputs that 
were necessary to meet this key user requirement. A summary of the user requirements (archived 
in the Design History File) include device functionality, compatibility, sterility, packaging, 
clinical usability, shelf life and product disposal. 
10.1.2 Preparation of LC Bead LUMI™ 
1.  During preparation of LC Bead LUMI™, use controlled aseptic conditions.
2.  Remove the plastic color coded flip cap from LC Bead LUMI™ vial but do not remove 
the metal ring around the stopper. With the spike of the ViaLok™ Vented Access Device 
centered to the rubber stopper of the vial, attach the device until the retention tabs snap on the 
LC Bead LUMI™ vial.

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Note: The ViaLok™ Vented Access Device is not for direct infusion and should only be used 
for transfer of the beads into a syringe. The access device size corresponds to vial diameter 
and is intended for use with ISO-594 compatible mating luers. LC Bead LUMI™ has only 
been tested in conjunction with ViaLok™ Vented Access Device.
3.  Remove and discard luer cap from the access device.
Note: To minimize risk of potential contamination, the ViaLok™ Vented Access Device 
protective cap shall remain attached to luer until accessed by the mating luer device.
4.  Attach a 10ml syringe to the luer lock of the ViaLok™ Vented Access Device.
5.  Invert vial and suspend the beads in solution by agitating in a swirling motion whilst 
drawing the LC Bead LUMI™ into the syringe.
6.  Once all the solution is transferred discontinue the agitation and maintain the vial in the 
inverted position to allow the beads to settle in the syringe. Return only the clear solution to 
the vial and repeat previous step to recover remaining beads from the vial. This process may 
be repeated twice if required.
Note: Small traces of LC Bead LUMI™ may be retained in the vial.
7. Once LC Bead LUMI™ has settled at the bottom of the syringe; disconnect the syringe 
from the ViaLok™ Vented Access Device. Expel all packing solution to waste or suitable 
container, leaving only LC Bead LUMI™ within the syringe
8. LC Bead LUMI™ should be prepared for administration using 100% non-ionic contrast 
agent to obtain an optimum suspension. Please refer to Table 2 of the IFU (Appendix C, 
Section 0) for recommended contrast agents.
9. Attach a connector to the syringe containing LC Bead LUMI™.  Using a 20ml syringe 
take up 20ml of contrast agent and connect to the 10 ml syringe containing the LC Bead 
LUMI™.
10. Gently mix LC Bead LUMI™ and contrast agent between syringes through the 
connector, until a homogenous suspension is achieved.
11. Remove 20ml syringe and replace with 3ml syringe for delivery. Mix between the 10ml 
and 3ml syringes using a connector to obtain homogenous suspension of LC Bead LUMI™. 
After the contents of the 10ml syringe is delivered, the process can be repeated by 
transferring the remaining suspension from the 20ml syringe to the 10ml syringe through a 
connector.
Note: Please ensure mixing is performed between each refill of the 3ml syringe.
10.1.3 Delivery Instructions
Please note that LC Bead LUMI™ will settle quickly in some contrast agents. Prior to and 
during delivery ensure that the beads are in suspension. Please note that larger beads have shorter 
suspension times than the smaller size ranges of LC Bead LUMI™.
1. Using standard techniques, position the delivery catheter within the target vessel and the 
catheter tip as close as possible to the treatment site to avoid inadvertent occlusion of non-
target vessels.

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2. Use a 3ml syringe to manage the injection pressure during catheter delivery of the LC 
Bead LUMI™ beads.
3. Slowly inject LC Bead LUMI™ solution into the delivery catheter under x-ray techniques 
such as fluoroscopy, CBCT and CT imaging while observing the bead distribution to avoid 
reflux. If there is no effect   on   the antegrade flow rate, choose a larger size of LC Bead 
LUMI™ and repeat the delivery process. Exercise conservative judgment in determining the 
embolization endpoint.
4. Where necessary, saline flushes can be used to ensure full delivery of the LC Bead 
LUMI™.
5. Upon completion of the treatment, remove the catheter while maintaining gentle suction so 
as not to dislodge LC Bead LUMI™ that may still be within the catheter lumen.
6. Discard any open unused LC Bead LUMI™ as well as any other ancillary equipment used 
in the procedure such as the ViaLok™ Vented Access Device, syringes, needles, catheters, 
etc., following the applicable local standard practice.
10.1.4 Labeling
10.1.5 Carton Label
Lot: 
XXXXXX
Expiry:
Yyyy-
510 (k) Clearance 152157              BTG-13-002 (XXX-XXXμm)   
Unique Product ID: 13002-001 to 13002-XXX 
CAUTION - Investigational device. Limited by Federal (US) law to investigational use.
Directions for Use: See Protocol and Instructions for use.

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mm
Storage Conditions: 20C – 250C ; Sterile, Do not re-use, Keep away from sunlight, Keep dry.
Manufactured by Biocompatibles UK Ltd a BTG International group company, Chapman House, 
Weydon Lane, Farnham, Surrey GU9 8QL.
10.1.6 Vial Label
Lot: XXXXXX
Expiry:
Yyyy-mm
510 (k) Clearance 152157    BTG-13-002 (XXX-XXXμm)   
Unique Product ID: 13002-001 to 13002-XXX 
Manufactured by Biocompatibles UK Ltd a BTG International group company, Chapman House, 
Weydon Lane, Farnham, Surrey GU9 8QL.

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11 REFERENCES 
1.
Lencioni, R., et al., Doxorubicin-eluting bead-enhanced radiofrequency ablation of 
hepatocellular carcinoma: a pilot clinical study. J Hepatol, 2008. 49(2): p. 217-22.
2.
Bruix, J. and M. Sherman, Management of hepatocellular carcinoma. Hepatology, 2005. 
42(5): p. 1208-36.
3.
Garrean, S., et al., Radiofrequency ablation of primary and metastatic liver tumors: a 
critical review of the literature. Am J Surg, 2008. 195(4): p. 508-20.
4.
Llovet, J.M., et al., Arterial embolisation or chemoembolisation versus symptomatic 
treatment in patients with unresectable hepatocellular carcinoma: a randomised 
controlled trial. Lancet, 2002. 359(9319): p. 1734-9.
5.
Varela, M., et al., Chemoembolization of hepatocellular carcinoma with drug eluting 
beads: Efficacy and doxorubicin pharmacokinetics. Journal of Hepatology, 2007. 46(3): 
p. 474-481.
6.
Malagari, K., et al., Transarterial chemoembolization of unresectable hepatocellular 
carcinoma with drug eluting beads: Results of an open-label study of 62 patients. 
Cardiovascular and Interventional Radiology, 2008. 31(2): p. 269-280.
7.
Meza-Junco, J., et al., Locoregional radiological treatment for hepatocellular carcinoma; 
Which, when and how? Cancer Treat Rev, 2011.
8.
Liapi, E. and J.F.H. Geschwind, Transcatheter and ablative therapeutic approaches for 
solid malignancies. Journal of Clinical Oncology, 2007. 25(8): p. 978-986.
9.
Goldberg, S.N., et al., Ablation of liver tumors using percutaneous RF therapy. AJR Am 
J Roentgenol, 1998. 170(4): p. 1023-8.
10.
Goldberg, S.N., et al., Percutaneous radiofrequency tissue ablation: does perfusion-
mediated tissue cooling limit coagulation necrosis? J Vasc Interv Radiol, 1998. 9(1 Pt 1): 
p. 101-11.
11.
Patterson, E.J., et al., Radiofrequency ablation of porcine liver in vivo: effects of blood 
flow and treatment time on lesion size. Ann Surg, 1998. 227(4): p. 559-65.
12.
Yamada, R., et al., Hepatic artery embolization in 32 patients with unresectable 
hepatoma. Osaka City Med J, 1980. 26(2): p. 81-96.
13.
Liapi, E. and J.F.H. Geschwind, Chemoembolization for Primary and Metastatic Liver 
Cancer. Cancer Journal, 2010. 16(2): p. 156-162.
14.
Leyendecker, J.R. and G.D. Dodd, Minimally invasive techniques for the treatment of 
liver tumors. Seminars in Liver Disease, 2001. 21(2): p. 283-291.
15.
Wood, B.J., et al., Percutaneous tumor ablation with radiofrequency. Cancer, 2002. 
94(2): p. 443-51.
16.
Peng, Z.W., et al., A case-control study comparing percutaneous radiofrequency ablation 
alone or combined with transcatheter arterial chemoembolization for hepatocellular 
carcinoma. Eur J Surg Oncol, 2010. 36(3): p. 257-63.
17.
Morimoto, M., et al., Midterm outcomes in patients with intermediate-sized 
hepatocellular carcinoma: a randomized controlled trial for determining the efficacy of 
radiofrequency ablation combined with transcatheter arterial chemoembolization. 
Cancer, 2010. 116(23): p. 5452-60.
18.
Shibata, T., et al., Small hepatocellular carcinoma: is radiofrequency ablation combined 
with transcatheter arterial chemoembolization more effective than radiofrequency 
ablation alone for treatment? Radiology, 2009. 252(3): p. 905-13.

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19.
Gadaleta, C., et al., Single-step Therapy - Feasibility and Safety of Simultaneous 
Transarterial Chemoembolization and Radiofrequency Ablation for Hepatic 
Malignancies. In Vivo, 2009. 23(5): p. 813-820.
20.
Kim, J.H., et al., Medium-sized (3.1-5.0 cm) hepatocellular carcinoma: transarterial 
chemoembolization plus radiofrequency ablation versus radiofrequency ablation alone. 
Ann Surg Oncol, 2011. 18(6): p. 1624-9.
21.
Sommer, C.M., et al., Multimodal visibility (radiography, computed tomography, and 
magnetic resonance imaging) of microspheres for transarterial embolization tested in 
porcine kidneys. Invest Radiol, 2013. 48(4): p. 213-22.

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12 APPENDICES
12.1 APPENDIX A: FDA 510 (K) CLEARANCE FOR LC BEAD LUMI

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 12.2 APPENDIX C: LC BEAD LUMI™ RADIOPAQUE EMBOLIC BEAD INSTRUCTIONS FOR USE

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PACKAGE LABEL:
Catalogue number
Batch number/Lot number
Do not reuse
Attention see instructions for use
 
Steam Sterilized
Use-by date/Expiry
Protect from light/ Keep away from sunlight
Protect from moisture/ Keep dry
Do not freeze.  Store at 2-25oC.
Manufacturer

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Patents
US 6,652,883; US 6,676,971; US 7,070,809, Other patents pending
Manufactured by:
Biocompatibles UK Ltd, a BTG International group company
Chapman House, Weydon Lane, Farnham, Surrey, GU9 8QL,
United Kingdom
Tel:  +44 (0)1252 732 732, Fax: +44 (0)1252 732 777
http://www.btg-im.com
LC Bead LUMI is a trademark of Biocompatibles UK Ltd, a BTG International group company. BTG and the BTG roundel logo are registered trademarks 
of BTG International Ltd.