A Single Institution Pilot Study Using a Head and Neck Maskless Immobilization Device (MID) for Patients With Head and Neck Cancer or Intracranial Tumors
Phase: NA
Conditions: Brain and Nervous System, Intracranial Neoplasm, Head and Neck Cancer
Sponsor: Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

Pilot MID Study 
 
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Protocol IRB# 16D.557 
 
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THOMAS JEFFERSON UNIVERSITY 
Sidney Kimmel Cancer Center 
 
A SINGLE INSTITUTION PILOT STUDY USING A HEAD AND NECK MASKLESS 
IMMOBILIZATION DEVICE (MID) FOR PATIENTS BEING TREATED FOR HEAD AND 
NECK CANCERS OR INTRACRANIAL TUMORS WHO REQUIRE RADIATION THERAPY 
 
Principal Investigator: 
Voichita Bar-Ad, MD 
Radiation Oncology 111 S. 11th Street, Suite G-301 Bodine Bldg, 
Philadelphia, PA 19107 
215-955-6702 
Co-Investigator(s): 
 
 
 
 
 
 
 
Non consenting  
Co-Investigator: 
 
 
Wenyin Shi, MD, PhD 
111 S. 11th Street, Suite G-301 Bodine Center 
215-955-6702 
 
Maria Werner-Wasik, MD 
111 S. 11th Street, Suite G-301 Bodine Center 
215-955-6702 
 
Nina Martinez, MD 
111 S. 11th Street, Suite G-301 Bodine Center 
215-955-6702 
 
 
 
Cheng Peng, PhD 
111 S. 11th Street, Suite G-301 Bodine Center 
215-955-9290 
 
Funding Sponsor: 
N/A 
IND/IDE Holder: 
N/A 
IND/IDE Number: 
N/A 
Study Product: 
Maskless Immobilization Device 
Protocol IDs: 
JeffTrial # 8994 
CCRRC # 2016-044 
IRB Control # 16D.557 
 

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Version Number: 
Version Date: 
1.0 
01/29/2016 
2.0 
09/10/2016 
3.0 
01/27/2017 
3.1 
05/09/2017 
4.0 
07/26/2017 
4.1 
08/25/2017 
4.2 
11/29/2017 
5.0 
02/13/2018 
6.0 
07/12/2018 
6.0.1 
08/07/2018 
6.1 
09/24/2018 
7.0 
02/12/2019 
7.1 
02/04/2020 
 
CONFIDENTIAL 
This document is confidential and the property of THOMAS JEFFERSON UNIVERSITY. 
No part of it may be transmitted, reproduced, published, or used by other persons 
without prior written authorization from the study sponsor. 
 

Pilot MID Study 
 
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Table of Contents 
Signature Page .......................................................................................................................... 7 
Statement of Compliance ........................................................................................................... 7 
List of Abbreviations ................................................................................................................... 8 
Study Summary ......................................................................................................................... 9 
1 
Introduction .........................................................................................................................12 
1.1 
Background Information ..............................................................................................12 
1.2 
Rationale for the Proposed Study ...............................................................................13 
1.3 
Potential Risks and Benefits .......................................................................................14 
1.3.1 Potential Risks.........................................................................................................14 
1.3.2 Benefits ...................................................................................................................14 
2 
Study Objectives .................................................................................................................15 
2.1 
Objectives ...................................................................................................................15 
2.1.1 Primary ....................................................................................................................15 
2.1.2 Secondary ...............................................................................................................15 
2.2 
Endpoints/Outcome Measures ....................................................................................15 
2.2.1 Primary ....................................................................................................................15 
2.2.2 Secondary ...............................................................................................................15 
2.2.3 Exploratory ..............................................................................................................15 
3 
Study Design ......................................................................................................................15 
3.1 
Characteristics ............................................................................................................16 
3.2 
Number of Subjects ....................................................................................................16 
3.3 
Duration of Therapy ....................................................................................................16 
3.4 
Duration of Follow Up .................................................................................................16 
3.5 
Study Timeline ............................................................................................................16 
3.5.1 Primary Completion .................................................................................................16 
3.5.2 Study Completion ....................................................................................................16 

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4 
Study Enrollment and Withdrawal .......................................................................................16 
4.1 
Eligibility Criteria .........................................................................................................16 
4.1.1 Inclusion Criteria ......................................................................................................16 
4.1.2 Exclusion Criteria ....................................................................................................16 
4.2 
Strategies for Recruitment and Retention ...................................................................17 
4.3 
Subject Withdrawal .....................................................................................................17 
4.3.1 Reasons for Withdrawal ..........................................................................................17 
4.3.2 Handling of Subject Withdrawals or Subject Discontinuation of Study Intervention ..17 
4.4 
Premature Termination or Suspension of Study ..........................................................17 
5 
Study Intervention ...............................................................................................................18 
5.1 
Study Product .............................................................................................................18 
5.2 
Study Product Description ...........................................................................................18 
5.2.1 Acquisition ...............................................................................................................18 
5.2.2 Product Storage and Stability ..................................................................................18 
5.3 
Study Procedural Intervention(s) Description ..............................................................18 
5.4 
Administration of Procedural Intervention ....................................................................19 
5.5 
Procedures for Training of Clinicians on Procedural Intervention ................................19 
5.6 
Assessment of Clinician and/or Subject Compliance with Study Procedural Intervention
 
19 
6 
Study Schedule ..................................................................................................................19 
6.1 
Pretreatment Period/Screening ...................................................................................19 
6.2 
Enrollment/Baseline ....................................................................................................19 
6.3 
Treatment Period ........................................................................................................20 
6.4 
End of Treatment Study Procedures ...........................................................................20 
6.5 
Withdrawal Visit/Discontinuation of Therapy ...............................................................20 
7 
Study Procedures and Evaluations .....................................................................................20 
7.1 
Study Procedures/Evaluations ....................................................................................20 

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8 
Evaluation of Safety ............................................................................................................20 
8.1 
Specification of Safety Parameters .............................................................................20 
8.1.1 Unanticipated Problems ..........................................................................................20 
8.1.2 Adverse Events .......................................................................................................21 
8.1.3 Serious Adverse Events ..........................................................................................21 
8.2 
Safety Assessment and Follow-Up .............................................................................21 
8.3 
Recording Adverse Events ..........................................................................................22 
8.3.1 Relationship to Study Intervention ...........................................................................22 
8.3.2 Expectedness ..........................................................................................................22 
8.3.3 Severity of Event .....................................................................................................22 
8.4 
Safety Reporting .........................................................................................................23 
8.4.1 Unanticipated Problem Reporting to IRB .................................................................23 
8.4.1 Adverse Event Reporting to IRB ..............................................................................23 
8.4.2 Serious Adverse Event Reporting to IRB .................................................................23 
8.4.3 Reporting of Pregnancy ...........................................................................................23 
8.5 
Halting Rules ..............................................................................................................23 
9 
Study Oversight ..................................................................................................................24 
10 
Clinical Site Monitoring and Auditing ..............................................................................24 
11 
Statistical Considerations ...............................................................................................24 
11.1 
Study Hypotheses .......................................................................................................24 
11.2 
Analysis Plans ............................................................................................................24 
11.3 
Sample Size Considerations .......................................................................................25 
12 
Source Documents and Access to Source Data/Documents ..........................................25 
13 
Quality Control and Quality Assurance ...........................................................................26 
14 
Ethics/Protection of Human Subjects ..............................................................................26 
14.1 
Ethical Standard .........................................................................................................26 

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14.2 
Institutional Review Board ...........................................................................................26 
14.3 
Informed Consent Process ..........................................................................................26 
14.4 
Exclusion of Women, Minorities, and Children (Special Populations) ..........................27 
14.5 
Subject Confidentiality ................................................................................................27 
14.6 
Future Use of Stored Specimens and Other Identifiable Data .....................................27 
15 
Data Handling and Record Keeping ...............................................................................27 
15.1 
Data Management Responsibilities .............................................................................27 
15.2 
Data Capture Methods ................................................................................................28 
15.3 
Study Records Retention ............................................................................................28 
15.4 
Protocol Deviations .....................................................................................................28 
16 
Study Finances ...............................................................................................................28 
16.1 
Funding Source ..........................................................................................................28 
16.2 
Conflict of Interest .......................................................................................................28 
16.3 
Subject Stipends or Payments ....................................................................................28 
17 
Publication and Data Sharing Policy ...............................................................................28 
18 
Literature References .....................................................................................................29 
Appendices ...............................................................................................................................30 
APPENDIX A: SCHEDULE OF EVENTS ..................................................................................30 
 
 
 
 
 
 
 
 

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Signature Page 
The signature below constitutes the approval of this protocol and the attachments, and 
provides the necessary assurances that this trial will be conducted according to all 
stipulations of the protocol, including all statements regarding confidentiality, and 
according to local legal and regulatory requirements and applicable US federal 
regulations and ICH guidelines. 
Principal Investigator: 
Signed: 
 
Date:  
Name: 
Voichita Bar Ad 
Title:  
Associate Professor 
Statement of Compliance 
This study will be conducted in accordance with the International Conference on Harmonisation 
guidelines for Good Clinical Practice (ICH E6), the Code of Federal Regulations on the 
Protection of Human Subjects (45 CFR Part 46), and Thomas Jefferson University research 
policies 
 
 
 

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List of Abbreviations 
AE 
Adverse Event/Adverse Experience 
CFR 
Code of Federal Regulations 
CIOMS 
Council for International Organizations of Medical Sciences 
CONSORT 
Consolidated Standards of Reporting Trials 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
DSMC 
Data and Safety Monitoring Committee 
DSMP 
Data and Safety Monitoring Plan 
FDA 
Food and Drug Administration 
FWA 
Federalwide Assurance 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IDE 
Investigational Device Exemption 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
MedDRA 
Medical Dictionary for Regulatory Activities 
MOP 
Manual of Procedures 
N 
Number (typically refers to subjects) 
PHI 
Protected Health Information 
PI 
Principal Investigator 
QA 
Quality Assurance 
QC 
Quality Control 
SAE 
Serious Adverse Event/Serious Adverse Experience 
SOP 
Standard Operating Procedure 
UP 
Unanticipated Problem 
NCI 
National Cancer Institute 
SKCC 
CRO 
MID 
CBCT 
DRR 
RT 
KV 
Sidney Kimmel Cancer Center 
Clinical Research Organization 
Maskless immobilization device 
Cone Beam Computer Tomography 
Digitally constructed radiography 
Radiation Therapy 
kilovoltage 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Summary 
 
Title: 
A SINGLE INSTITUTION PILOT STUDY USING A HEAD AND 
NECK MASKLESS IMMOBILIZATION DEVICE (MID) FOR 
PATIENTS BEING TREATED FOR HEAD AND NECK CANCERS 
OR INTRACRANIAL TUMORS WHO REQUIRE RADIATION 
THERAPY 
Précis: 
Patients undergoing radiation therapy (RT) for head and neck 
cancers or intracranial tumors will undergo CT simulation and port 
films with the standard thermoplastic mask. On two separate 
treatment days they will be positioned with the MID after treatment is 
delivered with thermoplastic mask setup. Cone beam computed 
tomography (CBCTs) imaging obtained using the RT treating 
machine will be used to determine degree of setup variance. No RT 
will be delivered to patients while positioned with the MID. 
Objectives: 
 
Primary: The primary objective of this study is to determine the setup 
accuracy and reproducibility of the MID in patients being treated for 
head and neck cancers or intracranial tumors who require radiation 
therapy. 
 
Secondary: To assess the patient comfort and quality of life using 
the MID when compared to the standard thermoplastic mask. 
Population: 
24 male or female patients who are at least 18 years old, and are 
being treated for head and neck cancers or intracranial tumors which 
requires radiation therapy.  
Phase: 
Pilot  
Number of Sites: 
1 (Thomas Jefferson University) 
Description of 
Intervention: 
Maskless immobilization device (MID) that immobilizes the head and 
neck of a patient for RT with the use of two straps (one over the 
forehead and the other over the chin).  
Study Duration: 
50 months 
Subject Participation 
Duration: 
2-7 weeks 
Estimated Time to 
Complete 
Enrollment: 
48 months 

Pilot MID Study 
 
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Schematic of Study Design: 
Prior to  
Enrollment 
Day -7 
 
 
 
Visit 1 
Day 1 
 
 
 
Visit 2 
Day 8 
 
 
Visit 3 
Day 8 ± 5 
 
 
 
Visit 4 
Day 15 ± 5 
 
 
 
 
 
Visit 5 
Last day of treatment 
 ± 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total N:Obtain informed consent. Screen potential subjects by inclusion and 
exclusion criteria; obtain history, document. 
CT simulation with thermoplastic mask and MID for radiation treatment planning. 
Patient survey to assess comfort of MID. 
 
Treatment with thermoplastic mask. CBCT imaging for setup in 
thermoplastic mask. Setup only with MID. CBCT imaging for setup 
verification. 
Assess for adverse events 
List analyses to be performed 
 
Port films with thermoplastic mask 
Treatment with thermoplastic mask. CBCT imaging for setup in 
thermoplastic mask. Setup only with MID. CBCT imaging for setup 
verification. 

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1 Introduction 
1.1 
Background Information 
There are more than 59,000 men and women in the US diagnosed with head and neck 
cancer and more than 23,000 new cases of brain tumors every year in US1, 2. Moreover, 
the estimates of brain metastases incidence vary from 20 to 50% in cancer patients. 
Many of the above patient groups will require radiation therapy (RT) at some point in 
their care. 
Patients receiving RT to the head and neck require immobilization to ensure 
reproducible setup accuracy. The current standard for head and neck immobilization in 
RT is a thermoplastic mask3.The thermoplastic mask conforms to the patient’s face and 
neck anatomy and hardens, allowing a rigid frame that is flush against the patient’s 
body for daily radiation treatment. Specific limitations of this current standard include 
poor tolerance by claustrophobic patients, requiring daily benzodiazepines or cutting 
holes in the mask which can compromise setup accuracy. Further, the mask system, 
while flush against the patient’s skin, does allow for different degrees of neck flexion, 
which can result in error in patient positioning3. Currently each mask costs 
approximately $2504 and requires replacement if the patient loses too much weight or 
does not line up properly for daily setup.  
Occasionally straps are used to immobilize patients. This can be in the form of adhesive 
tape for skin cancer treatments using brachytherapy applicators, where the overall 
position of the patient is not as important as that the applicator covers the skin lesion. 
The tape serves as a crude immobilization device for the patients head or extremity. 
Velcro straps are used to immobilize shoulders in patients undergoing radiation 
treatment to the head and neck. Straps are primarily used when millimeter precision in 
immobilization is not required, as it is difficult to quantify how much pressure is required 
to immobilize without causing discomfort to the patient. There is a fine balance between 
the amount of tension needed to immobilize the patient while maintaining patient 
comfort. 
The proposed MID is a device that will allow the investigator to immobilize the patient 
without the use of a mask that covers the patient’s face. Previous researchers have 
attempted to use maskless immobilization but the setup precision has historically been 
questioned5. The current technology that is under review for provisional patent status 
(patent pending) will ensure reproducible immobilization in a non-invasive manner. The 
intellectual property under review is a device that allows quantification of the 
immobilization force and vectors. The patient will be positioned on a standard radiation 
therapy head rest and immobilized with two straps. Strap length will be adjusted by 
ratchets.  Force gauges will be used to quantify how much pressure is applied through 
the strap, which allows the safe application of the strap, quantification of how much 

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tension is required for immobilization and reproducibility in subsequent treatment 
setups. Due to the force gauge quantifying the strap tension the risk of excess 
tension/pressure on the patient is theoretically less than strap application without the 
force gauge. This combination of commercially available technologies is the first 
application of its kind. The strap materials are regular tie down straps constructed of 
polypropylene, nylon or polyester. They are commercially available and are not the 
subject of intellectual property. Force gauges are also commercially available and will 
not have contact with the patient.. 
In regard to cost, after the initial cost of purchase for the MID (approximately $50), the 
MID setup may be significantly cheaper than current thermoplastic masks. Each MID 
will require only two straps of material per patient. The cost may be as low as $5 / 
patient, in contrast to the current price tag of $250 / patient. Force gauge cost can vary 
from $20 to $1000. However, they will be part of the radiation table setup and not need 
to be purchased more than once.  
This research will potentially lead to an additional standard of care for immobilization in 
head and neck RT. It is significantly less costly than the current standard of care. It will 
be more tolerable to patients with fears of enclosed spaces or objects on their faces. If it 
is comparable to the thermoplastic mask in regard to setup reproducibility, it may even 
replace thermoplastic masks. 
 
1.2 
Rationale for the Proposed Study 
The combination of the force gauge and strap for patient immobilization is the subject of 
intellectual property and does not exist outside this protocol. We propose that this 
combination allows for a safer application and reproducible immobilization of the patient 
compared to straps without force gauge quantification of pressure applied. However, the 
purpose of this study is not to evaluate safety, as the risk to patient with strap 
immobilization is extremely low. No radiation therapy will be delivered to the patient with 
MID immobilization. 
The MID will be applied to the patient at CT simulation and two points during the 
treatment schedule, and no treatment will be delivered while the MID is applied to the 
patient. This will be two arbitrary time points to assess the degree of setup error 
compared to the gold standard of the thermoplastic mask. The patient population will be 
those patients being treated for head and neck cancers or intracranial tumors that 
requires radiation therapy (RT). This population is selected as the treatment fields are 
simple, and the setup position can be accurately verified by CBCT.  
SPECIFIC AIM 1: To assess setup accuracy and reproducibility of the novel MID. We 
hypothesize that the degree of error with the novel MID will be similar to that of a 
thermoplastic mask.  

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SPECIFIC AIM 2: To assess the patient comfort and quality of life using the MID. We 
hypothesize that patients will have decreased claustrophobia symptoms and/or anxiety 
when immobilized with the MID compared to the thermoplastic mask. 
1.3 
Potential Risks and Benefits 
1.3.1 
Potential Risks 
Some patients may experience anxiety or claustrophobia but this would likely be to a 
lesser degree than the thermoplastic mask in which they receive daily radiation 
treatments. Some patients may experience mild discomfort with the strap application to 
their foreheads and chins.  
CBCTs are used in a regular basis for set up verification and deliver small amounts of 
additional radiation. 
Rationale for additional imaging: No patient will receive radiation treatment with the 
experimental MID. Patient setup reproducibility and accuracy will be assessed by 
CBCT. Each day a patient is treated with radiation treatment, they are positioned to 
replicate the patient setup on the day the CT for radiation treatment planning was 
obtained. To verify this setup, images such as CBCTs can be obtained and compared to 
the original CT simulation scan. Since CTs are three dimensional, translational setup 
errors in the X, Y and Z axis can be quantified.  
We need to obtain two additional setup CBCTs on two different treatment days. The 
CBCT with the MID will allow us to compared the MID setup with the CT simulation 
scan. The CBCT with the thermoplastic mask will allow us to assess setup error of the 
gold standard compared to the CT simulation scan. We can then compare the error of 
the thermoplastic mask with the experimental MID. Patient safety and treatment will 
not be compromised as no treatments will be delivered with the MID. 
Safety of additional imaging: CBCTs are obtained by kV imaging. Each CBCT is 
approximately 5 cGy. The 4 additional CBCTs will add approximately 20 cGy to the 
patients overall radiation exposure. Patients receiving RT for primary brain tumors will 
be treated with 300x this dose (6000 cGy). Patients receiving radiation for head and 
neck cancers may receive doses of 6000-7000 cGy. Patients receiving RT for 
secondary/metastatic intracranial malignancies will receive 150x this dose (3000 cGy). 
Thus this additional imaging poses little if any risk to the patient and can ensure more 
accurate treatment setup and radiation delivery.  
1.3.2 
Benefits 
Potential benefits include decreased anxiety and/or claustrophobia compared to 
thermoplastic mask. 

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2 Study Objectives 
2.1 
Objectives 
2.1.1 
Primary 
To assess the setup accuracy and reproducibility of the MID in patients being treated for 
head and neck cancers or intracranial tumors who require radiation therapy.. 
2.1.2 
Secondary 
To assess the patient comfort and quality of life with the MID compared to the 
thermoplastic mask. 
2.2 
Endpoints/Outcome Measures 
2.2.1 
Primary 
The primary endpoints are to assess the setup accuracy and reproducibility with the 
MID. Accuracy will be measured by quantifying the difference in translational shifts from 
the daily setup to planning CT scan digitally reconstructed radiograph (DRR). The 
magnitude of shifts will be compared to the shifts required using the gold standard 
thermoplastic mask. 
2.2.2 
Secondary 
A secondary endpoint is to assess patient comfort and quality of life with the MID. The 
measurable outcome will be a questionnaire that assesses the patient’s pain, discomfort 
and level of anxiety when in the MID compared to when in the thermoplastic mask. 
2.2.3 
Exploratory 
3 Study Design 
This is a single-institution, pilot study using a MID for RT treatment immobilization of 
patients being treated for head and neck cancers or intracranial tumors who require 
radiation therapy.. The patient population will be outpatient based, all of them receiving 
RT to treat head and neck cancers or intracranial tumors, assessed by CBCT and patient 
QOL surveys over the duration of their radiation treatment. There will only be a single 
study arm in which all patients receive RT with the thermoplastic mask but also receive 
CBCT imaging with the MID to assess the setup accuracy and reproducibility. Patient 
tolerance of the MID will be assessed through a survey delivered the day of MID use. 
Setup accuracy will be evaluated by comparing translational shifts required with MID to 
shifts required with thermoplastic mask. The last QOL evaluation will be at the 
completion of the patient’s radiation treatment. No radiation therapy will be delivered 
with MID immobilization. 

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3.1 
Characteristics 
Patients being treated for head and neck cancers or intracranial tumors who require 
radiation therapy. 
3.2 
Number of Subjects 
24 patients 
3.3 
Duration of Therapy 
2-7 weeks. 
3.4 
Duration of Follow Up 
Only during radiation treatment (up to 7 weeks of therapy) 
3.5 
Study Timeline 
3.5.1 
Primary Completion 
Accrue patients over 48 months 
3.5.2 
Study Completion 
Completion of accrual and data analysis by 50 months  
4 Study Enrollment and Withdrawal 
4.1 
Eligibility Criteria 
4.1.1 
Inclusion Criteria 
Individuals must meet all of the following inclusion criteria in order to be eligible to 
participate in the study: 
• Patients being treated for head and neck cancers who require radiation therapy 
or intracranial tumors over a 2 to 7 week period of time. 
• Age ≥ 18 years old 
• Subjects are capable of giving informed consent or have an acceptable surrogate 
capable of giving consent on the subject’s behalf. 
• Provide signed and dated informed consent form 
 
4.1.2 
Exclusion Criteria 
An individual who meets any of the following criteria will be excluded from participation 
in this study: 

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• History of prior trauma or orthopedic surgery to the cervical vertebral column / 
spine, clinically significant and interfering with the RT planning process, as per 
the determination of the treating physicians. Patient requires a neck brace for 
medical reasons 
• Skull or bony defect in the area contacting the immobilization straps 
• RT delivered by clinical setup only (no CT simulation). 
4.2 
Strategies for Recruitment and Retention 
Patients with head and neck cancers or intracranial tumors who are candidates for 
receiving RT will be offered the participation in the study, by the treating radiation 
oncologists. Anticipate screening 30 patients for 24 patients in study.  
4.3 
Subject Withdrawal 
4.3.1 
Reasons for Withdrawal 
Subjects are free to withdraw from participation in the study at any time upon request. 
An investigator may terminate a study subject’s participation in the study if: 
• Any clinical adverse event (AE), laboratory abnormality, or other medical 
condition or situation occurs such that continued participation in the study would 
not be in the best interest of the subject. 
• The subject meets an exclusion criterion (either newly developed or not 
previously recognized) that precludes further study participation. 
• The patient will not complete radiation treatment; study closure; patient decision 
to withdraw from study; or in the judgment of the investigator, continued 
enrollment in the trial would not be in the best interest of the patient. 
4.3.2 
Handling of Subject Withdrawals or Subject Discontinuation of Study 
Intervention 
Patients will be assessed for any adverse events by treating physician on the last day of 
radiation treatment, as per the study schema. 
4.4 
Premature Termination or Suspension of Study 
This study may be suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, 
will be provided by the suspending or terminating party to investigator and regulatory 
authorities. If the study is prematurely terminated or suspended, the principal 
investigator will promptly inform the IRB and will provide the reason(s) for the 
termination or suspension.  
Circumstances that may warrant termination include, but are not limited to: 

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• Determination of unexpected, significant, or unacceptable risk to subjects. 
• Insufficient adherence to protocol requirements. 
• Data that is not sufficiently complete and/or evaluable.  
• Determination of futility. 
5 Study Intervention 
5.1 
Study Product 
Maskless immobilization device (MID) 
5.2 
Study Product Description 
MID is based on two straps that immobilize the head and neck by applying force to the forehead 
and chin. The product is currently under review for a provisional patent (patent pending). 
5.2.1 
Acquisition 
Product prototype was designed and created in the machine lab in the Department of 
Radiation Oncology. This is a new device that does not exist in the public domain. 
5.2.2 
Product Storage and Stability 
The Maskless Immobilization Device (MID) will be kept in a locked, secured location within the 
Department of Radiation Oncology at the Bodine Center. A code will be required to gain entry to 
the device storage location. 
Study Product Accountability 
Single device is used for multiple patients. Disposable guards/pads will ensure 
sanitation between each patient use. Assessing Subject Compliance with Study Product 
Administration 
If patients are undergoing setup with MID for two days during their treatment course 
then they will be deemed compliant. The MID will not be used during their standard of 
care treatment. Failure to comply with the MID days will be reported to the treating 
physician and investigators of this study. 
5.3 
Study Procedural Intervention(s) Description 
Patients will be immobilized in a MID. The device consists of two straps that apply 
pressure at the patient’s forehead and chin. The patient is lying with his/her head resting 
on a standard radiation head cup. Temporary skin markers (surgical marker and/or 
radiation setup sticker) will be used to reference the patient setup. Photos will be taken 
to show position of radiation setup markers. No radiation therapy will be delivered 
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5.4 
Administration of Procedural Intervention 
Radiation therapists, who position patients on the radiation treatment table, will be 
trained in the application of this device.  
5.5 
Procedures for Training of Clinicians on Procedural Intervention 
Radiation therapists will undergo training for MID use. Their application of the MID to a 
standardized patient will be evaluated by the investigators prior to independent use. 
5.6 
Assessment of Clinician and/or Subject Compliance with Study 
Procedural Intervention 
Investigators will directly observe the therapist use the technology on a standardized 
patient and during the first application on each patient. 
6 Study Schedule 
CT simulation  
Day 1 
Port films 
Day 8  
Fraction A 
Day 8 ± 5 
Fraction B 
Day 15 ± 5 
Thermoplastic mask 
immobilization 
Thermoplastic 
mask 
immobilization + 
CBCT 
Thermoplastic 
mask 
immobilization + 
CBCT 
Thermoplastic 
mask 
immobilization 
+ CBCT 
  
  
RT* 
RT* 
 MID 
  
MID + CBCT 
MID + CBCT 
*RT is standard of care and will only be given while patients are immobilized with the standard 
thermoplastic mask. 
6.1 
Pretreatment Period/Screening 
Screening Visit (Day -28 to -1) 
• Obtain and document consent from potential subject on consent form. 
• Review medical history to determine eligibility based on inclusion/exclusion 
criteria. 
• Schedule study visits for individuals who are eligible and available for the 
duration of the study.  
6.2 
Enrollment/Baseline 
Enrollment/Baseline Visit (Day 0) 
Verify inclusion/exclusion criteria. 

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Record results of complete physical examinations. 
6.3 
Treatment Period 
 
Visit 1, Day 1 
CT simulation with thermoplastic mask. CT simulation with MID. Survey for anxiety and 
comfort. Symptom directed physical examination. Record any adverse events. 
 
Visit 3, Day 8 ± 5 
MID application and setup verification with CBCT. Survey for anxiety and comfort. 
Symptom directed physical examination. Record any adverse events. 
 
Visit 4, Day 15 ± 5 
MID application and setup verification with CBCT. Survey for anxiety and comfort. 
Symptom directed physical examination. Record any adverse events. 
6.4 
End of Treatment Study Procedures 
Final Study Visit (Final Visit, Last day of RT± 5) 
Final visit should occur on the last day of treatment. Patient is assessed for any adverse 
events. No further follow-up designated. 
6.5 
Withdrawal Visit/Discontinuation of Therapy 
Assessment of any adverse events. 
7 Study Procedures and Evaluations 
7.1 
Study Procedures/Evaluations 
Patient medical history will be reviewed from chart and rule out prior neck and/or spine 
surgery. 
A physical examination will be performed, with attention to head and neck range of 
motion, strength and pain. 
8 Evaluation of Safety 
8.1 
Specification of Safety Parameters 
8.1.1 
Unanticipated Problems 
Unanticipated problems (UAPs) include, in general, any incident, experience, or 
outcome that meets the following criteria: 

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• unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
IRB-approved research protocol and informed consent document; and (b) the 
characteristics of the subject population being studied; 
UAPs are considered to pose risk to subjects or others when they suggest 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. 
8.1.2 
Adverse Events 
An adverse event is any untoward or unfavorable 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 the research, whether or not considered related to the subject’s 
participation in the research. 
8.1.3 
Serious Adverse Events 
A serious adverse event (SAE) is one that meets one or more of the following criteria: 
• Results in death 
• Is life-threatening (places the subject at immediate risk of death from the event 
as it occurred) 
• Results in inpatient hospitalization or prolongation of existing hospitalization 
• Results in a persistent or significant disability or incapacity 
• Results in a congenital anomaly or birth defect 
• An important medical event that may not result in death, be life threatening, or 
require hospitalization may be considered an SAE when, based upon appropriate 
medical judgment, the event may jeopardize the subject and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition. 
8.2 
Safety Assessment and Follow-Up 
The only portion of this study considered to be investigational is the maskless 
immobilization device (MID). Therefore, the only adverse events that will be reported 
are those related to the use of the MID.  
The PI will follow adverse events with start dates occurring any time after informed 
consent is obtained until 7 (for non-serious AEs) or 30 days (for SAEs) after the last day 
of study participation. At each study visit, the investigator (or designee) will inquire 
about the occurrence of AE/SAEs since the last visit. Events will be followed for 
outcome information until resolution or stabilization. 

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8.3 
Recording Adverse Events 
The following subsections detail what information must be documented for each 
adverse event occurring during the time period specified in Section 8.2 Safety 
Assessment and Follow-Up.  
The only portion of this study considered to be investigational is the maskless 
immobilization device (MID). Therefore, the only adverse events that will be reported 
are those related to the use of the MID.   
8.3.1 
Relationship to Study Intervention 
The relationship to study device (MID) or study participation must be assessed and 
documented for all adverse events. Evaluation of relatedness must consider etiologies 
such as natural history of the underlying disease, concurrent illness, concomitant 
therapy, study-related procedures, accidents, and other external factors.  
The following guidelines are used to assess relationship of an event to study 
intervention: 
1. Related (Possible, Probable, Definite) 
a. The event is known to occur with the study intervention. 
b. There is a temporal relationship between the intervention and event onset. 
c. The event abates when the intervention is discontinued. 
d. The event reappears upon a re-challenge with the intervention. 
2. Not Related (Unlikely, Not Related) 
a. There is no temporal relationship between the intervention and event 
onset. 
b. An alternate etiology has been established. 
8.3.2 
Expectedness 
The PI is responsible for determining whether an AE is expected or unexpected. An AE 
will be considered unexpected if the nature, severity, or frequency of the event is not 
consistent with the risk information previously described for the intervention. Risk 
information to assess expectedness can be obtained from preclinical studies, the 
investigator’s brochure, published medical literature, the protocol, or the informed 
consent document. 
8.3.3 
Severity of Event 
Adverse events will be graded for severity according to the Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0  

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8.4 
Safety Reporting 
The only portion of this study considered to be investigational is the maskless 
immobilization device (MID). Therefore, the only adverse events that will be reported 
are those related to the use of the MID.   
8.4.1 
Unanticipated Problem Reporting to IRB 
All incidents or events that meet criteria for unanticipated problems (UAPs), as defined 
in Section 8.1.1Unanticipated Problems, require the creation and completion of an 
unanticipated problem report form (OHR-20).  
UAPs that pose risk to subjects or others, and that are not AEs, will be submitted to the 
IRB on an OHR-20 form via the eazUP system within 5 working days of the investigator 
becoming aware of the event.  
UAPs that do not pose risk to subjects or others will be submitted to the IRB at the next 
continuing review.  
8.4.1 Adverse Event Reporting to IRB 
Grade 1 AEs are not required to be reported to the IRB.  
Grade 2 AEs will be reported to the IRB at the time of continuing review if, in the opinion 
of the investigator, they represent events that exceed expected frequency or in some 
other way are judged to be unexpected and possibly associated with increased risk.  
Other adverse events will only be reported if deemed related to the IRB. 
8.4.2 
Serious Adverse Event Reporting to IRB 
SAEs will be reported to the IRB on OHR-10 forms via the electronic reporting system 
(eSAEy) according to the required time frames described below. 
Grade 3-4 AEs that are unexpected and deemed to be at least possibly or definitely 
related to the study will be reported to the IRB within 2 working days of knowledge of 
the event. 
Grade 3-4 AEs that are deemed unrelated to the study will not be reported.  
Grade 5 AEs that are deemed unrelated to the study will not be reported. 
8.4.3 
Reporting of Pregnancy 
No patients receiving radiation therapy should be pregnant. Department policy requires 
negative pregnancy test prior to starting radiation therapy. No additional protocol effort 
needed. 
8.5 
Halting Rules 

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Study will be halted in the event of one serious adverse event definitely or probably 
related to the MID. 
9 Study Oversight 
In addition to the PI’s responsibility for oversight, study oversight will be under the 
direction of the SKCC’s Data and Safety Monitoring Committee (DSMC).The DSMC 
operates in compliance with a Data and Safety Monitoring Plan (DSMP) that is 
approved by the Clinical Trials Oversight Committee (CTOC).  
10 Clinical Site Monitoring and Auditing 
Clinical site monitoring and auditing is conducted to ensure that the rights of human 
subjects are protected, that the study is implemented in accordance with the protocol 
and/or other operating procedures, and that the quality and integrity of study data and 
data collection methods are maintained. Monitoring and auditing for this study will be 
performed in accordance with the SKCC’s Data and Safety Monitoring Plan (DSMP) 
developed by the SKCC Data and Safety Monitoring Committee (DSMC).The DSMP 
specifies the frequency of monitoring, monitoring procedures, the level of clinical site 
monitoring activities (e.g., the percentage of subject data to be reviewed), and the 
distribution of monitoring reports. Some monitoring activities may be performed 
remotely, while others will take place at the study site(s). Appropriate staff will conduct 
monitoring activities and provide reports of the findings and associated action items in 
accordance with the details described in the DSMP. 
11 Statistical Considerations 
11.1 Study Hypotheses 
Primary objective: To establish that the new device is no worse than the old device in 
term of the setup accuracy and reproducibility. Accuracy will be measured by 
quantifying the difference in translational shifts from the daily setup to planning CT scan 
digitally reconstructed radiograph (DRR). The magnitude of shifts will be compared to 
the shifts required using the gold standard thermoplastic mask. 
Secondary objective: To establish that the new device is no worse than the old device 
in term of increasing patients’ comfort and reduce patients’ anxiety. The measurable 
outcome will be a questionnaire that assesses the patient’s pain, discomfort and level of 
anxiety when in the MID compared to when in the thermoplastic mask. 
11.2 Analysis Plans 
For the primary objective, the magnitude of the single vector that depicts the degree of 
setup discrepancy from CT simulation will be collected for each patient on each day the 
MID is applied (for both the thermoplastic mask and the MID). The 90% lower 

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confidence limit of the absolute discrepancy, as well as the 90% higher confidence limit 
of the standard error, will serve as a conservative estimate of the mean and standard 
deviation.  Based on literature, the thermoplastic mask results in a need for translational 
shifts on average of 3.5mm with a standard deviation of 1.2mm6, 7.  We propose to use 
a total of 24 patients in the pilot study aiming to establish that the new device is no 
worse than the old device with a non-inferiority margin of 0.5mm, assuming the new 
device requires a mean translational error adjustment of patients by 2.5mm with the 
standard deviation of 1.2mm at 91% power and a Type-I-Error rate of 5%. 
For the secondary objective, we will collect the preference survey scores for the 
thermoplastic mask versus the MID (survey results) from the same patients participated 
in the primary objective. The preference scores will be compared using cumulative 
logistic regression model. 
11.3 Sample Size Considerations 
Sample size calculation for the pilot study has been provided in Section 11.2.   
12 Source Documents and Access to Source Data/Documents 
Study staff will maintain appropriate medical and research records for this study, in 
compliance with ICH E6, and regulatory and institutional requirements for the protection 
of confidentiality of subject information. Study staff will permit authorized 
representatives of SKCC and regulatory agencies to examine (and when required by 
applicable law, to copy) research records for the purposes of quality assurance reviews, 
audits, and evaluation of the study safety, progress and data validity. The only source 
documents outside of standard medical records available in the EMR will be the patient 
surveys and record of setup measurement shifts. 

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13 Quality Control and Quality Assurance 
The PI or a Co-I’s will be present at the time of CBCT for patients undergoing MID 
placement for the first placement. Radiation therapists will be supervised by the PI or a 
Co-I for at least 2 MID placements, and shown proficiency in its use (correct application 
and patient setup) before they are not supervised. 
Translational shifts will be verified by the PI or a Co-I and recorded in a secure 
electronic spreadsheet. Entries will be verified by radiation therapists. Surveys will be 
reviewed by clinic nurses to ensure all questions have been completed. Survey data will 
be recorded. 
14 Ethics/Protection of Human Subjects 
14.1 Ethical Standard 
The investigator will ensure that this study is conducted in full conformity with the 
principles set forth in The Belmont Report: Ethical Principles and Guidelines for the 
Protection of Human Subjects of Research, as drafted by the US National Commission 
for the Protection of Human Subjects of Biomedical and Behavioral Research (April 18, 
1979) and codified in 45 CFR Part 46 and/or the ICH E6. 
14.2 Institutional Review Board 
The protocol, informed consent form(s), recruitment materials, and all subject materials 
will be submitted to the IRB for review and approval. Approval of both the protocol and 
the consent form must be obtained before any subject is enrolled. Any amendment to 
the protocol will require review and approval by the IRB before the changes are 
implemented in the study. 
14.3 Informed Consent Process 
Informed consent is a process that is initiated prior to the individual agreeing to 
participate in the study and continues throughout study participation. Extensive 
discussion of risks and possible benefits of study participation will be provided to 
subjects and their families, if applicable. A consent form describing in detail the study 
procedures and risks will be given to the subject. Consent forms will be IRB-approved, 
and the subject is required to read and review the document or have the document read 
to him or her. The investigator or designee will explain the research study to the subject 
and answer any questions that may arise. The subject will sign the informed consent 
document prior to any study-related assessments or procedures. Subjects will be given 
the opportunity to discuss the study with their surrogates or think about it prior to 
agreeing to participate. They may withdraw consent at any time throughout the course 
of the study. A copy of the signed informed consent document will be given to subjects 
for their records. The rights and welfare of the subjects will be protected by emphasizing 
to them that the quality of their clinical care will not be adversely affected if they decline 

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to participate in this study. The consent process will be documented in the clinical or 
research record. 
14.4 Exclusion of Women, Minorities, and Children (Special Populations) 
Children are excluded from this study as they often require general anesthesia or 
sedation during radiation therapy to tolerate the standard thermoplastic mask. Both 
males and females patients with head and neck cancers or intracranial tumors who 
require RT will be eligible for the trial.  
14.5 Subject Confidentiality 
Subject confidentiality is strictly held in trust by the investigators, study staff, and the 
sponsor(s) and their agents. 
The study protocol, documentation, data, and all other information generated will be 
held in strict confidence. No information concerning the study or the data will be 
released to any unauthorized third party without prior written approval of the sponsor. 
The study monitor or other authorized representatives of the sponsor may inspect all 
study documents and records required to be maintained by the investigator, including 
but not limited to, medical records (office, clinic, or hospital) for the study subjects. The 
clinical study site will permit access to such records. 
14.6 Future Use of Stored Specimens and Other Identifiable Data 
Survey data will be held in a secure network drive until 3 years after the completion of 
the study. 
15 
Data Handling and Record Keeping 
The investigators are responsible for ensuring the accuracy, completeness, legibility, 
and timeliness of the data reported. All source documents should be completed in a 
neat, legible manner to ensure accurate interpretation of data. The investigators will 
maintain adequate case histories of study subjects, including accurate case report 
forms (CRFs), and source documentation. 
Data will be entered into an electronic spreadsheet by a study team member and 
verified by a Radiation Therapist. Data will be stored on password protected computers 
on internal network drives. Survey responses will be inputted electronically by a study 
team member. Electronic copies of records will be kept for 3 years after completion of 
study. 
15.1 Data Management Responsibilities 
Data collection and accurate documentation are the responsibility of the study staff 
under the supervision of the investigator. All source documents and laboratory reports 
must be reviewed by the study team and data entry staff, who will ensure that they are 
accurate and complete. Unanticipated problems and adverse events must be reviewed 
by the investigator or designee. 

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15.2 Data Capture Methods 
As described in 15.1, data will be recorded electronically and stored on a password 
protected, secure network drive.  
Types of Data 
Translational data and questionnaire data will be collected. 
15.3 Study Records Retention 
Study records will be maintained for at least three years. 
15.4 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol, Good Clinical 
Practice, or Manual of Procedures requirements. The noncompliance may be on the 
part of the subject, the investigator, or study staff. As a result of deviations, corrective 
actions are to be developed by the study staff and implemented promptly. 
All deviations from the protocol must be addressed in study subject source documents 
and promptly reported to the IRB and other regulatory bodies according to their 
requirements. 
16 Study Finances 
16.1 Funding Source 
Study will be financed in cooperation with the Department of Radiation Oncology and 
Thomas Jefferson University Hospital Innovation Pillar. 
16.2 Conflict of Interest 
Any investigator who has a conflict of interest with this study (patent ownership, 
royalties, or financial gain greater than the minimum allowable by their institution, etc.) 
must have the conflict reviewed by a properly constituted Conflict of Interest Committee 
with a Committee-sanctioned conflict management plan that has been reviewed and 
approved by the study sponsor prior to participation in this study. All Jefferson 
University Investigators will follow the TJU Conflicts of Interest Policy for Employees 
(107.03). 
16.3 Subject Stipends or Payments 
Subjects will not receive any stipends or payments for participation in this study. 
17 Publication and Data Sharing Policy 

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The PI will have primary oversight and responsibility for the publication of these trial 
results. As this is a small feasibility study it is not required to be reported to the FDA. 
There is no NIH funding involved in this trial so it is not subject to NIH public access 
guidelines. 
18 Literature References 
1. Head and Neck Cancer - Statistics [Internet]. CancerNet [cited 2015 Aug 18] 
Available from: http://www.cancer.net/cancer-types/head-and-neck-cancer/statistics 
2. Brain Tumor - Statistics [Internet]. CancerNet [cited 2015 Aug 18] Available from: 
http://www.cancer.net/cancer-types/brain-tumor/statistics 
3. Donato K, Leszczynski K, Fleming K: A comparative evaluation of two head and neck 
immobilization devices using electronic portal imaging. Br J Radiol 79:158–161, 2006 
4. Thermoplastics [Internet][cited 2015 Aug 18] Available from: 
http://www.civco.com/ro/products/Thermoplastics.htm 
5. Gevaert T, Verellen D, Tournel K, et al: Setup Accuracy of the NovalisExacTrac 
6DOF System for Frameless Radiosurgery. Int J RadiatOncol 82:1627–1635, 2012 
6. Weltens C, Kesteloot K, Vandevelde G, et al: Comparison of plastic and Orfit® masks 
for patient head fixation during radiotherapy: Precision and costs. Int J RadiatOncol 
33:499–507, 1995 
7. Amelio D, Winter M, Habermehl D, et al: Analysis of inter- and intrafraction accuracy 
of a commercial thermoplastic mask system used for image-guided particle radiation 
therapy. J Radiat Res (Tokyo) 54 Suppl 1:i69–76, 2013 

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Appendices 
 
APPENDIX A: SCHEDULE OF EVENTS 
Procedures 
Screening /Baseline 
(Day –28 to) 
Study Visit 1 
(Day 1) 
Study Visit 3 
(Day 8 ± 5) 
Study Visit 4 
(Day 15 ± 5) 
Visit 5 
Last day of 
treatment 
± 5 Days 
Signed Consent Form 
X 
 
 
 
 
Assessment of Eligibility Criteria 
X 
 
 
 
 
Review of Medical 
X 
 
 
 
 
CT SimulationA 
 
X 
 
 
 
Study Intervention (MID)B 
 
X 
X 
X 
 
Questionnaire 
 
X 
X 
X 
 
Physical 
Examination 
Complete 
X 
 
 
 
 
Symptom-
Directed 
 
X 
X 
X 
 
Assessment of Adverse Events 
 
 
X 
X 
X 
A. CT Simulation will be with both thermoplastic mask and with MID 
B. Setup verification for MID application will be done with CBCT. No treatment to 
be given to patients with MID immobilization. 
 
 
 
 
 
 
 
 

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APPENDIX B: PROMIS 
 
 
 

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