Conditions: Breast Cancer
Keywords: external beam radiotherapy breast cancer
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 28
Healthy volunteers: no

Brief summary:
This will be a randomized, double blind, vehicle-controlled evaluation of the effectiveness and safety of HylaCareTM. The study will employ the patient as her own control, a commonly used method for the evaluation of topical dermatologic agents. Each patient will be randomized blindly as to whether the study serum will be applied to the medial or lateral portion of the treated breast, using the nipple as the dividing line. The product and placebo will also be applied to the contra-lateral breast in the same fashion, as a further control. The study drug and placebo will be applied three (3) times daily.

Detailed description:
Patients will be allocated to the treatment using a randomized permuted block. There will be no stratification. Patients will be randomized to receive the investigational product to be applied to either the medial (inside) or lateral (outside) portion of the breast, a placebo product will be used on the other side. Patients and clinical investigators will be blinded to the treatment assignments.

Arms:
arm 1: HylaCare cream Each patient will be randomized blindly as to whether the study serum will be applied to the medial or lateral portion of the treated breast, using the nipple as the dividing line. The product and placebo will also be applied to the contra-lateral breast in the same fashion, as a further control. The study drug and placebo will be applied three (3) times daily, but not within 4 hours prior to radiation treatment. arm 2: The patient is her own control.

Interventions: intervention 1: HylaCare intervention 2: Placebo
Intervention descriptions: intervention 1: cream intervention 2: placebo

Protocol document:
Prot_000.pdf: 
Official Title: Randomized, Double-Blind, Vehicle-Controlled Pilot Study of the Efficacy and Safety of 
HylaCareTM in the Treatment of Acute Skin Changes in Patients Undergoing External Beam 
Radiotherapy for Tumors of the Breast. 
 
NCT02165605 
Protocol Date: May 07, 2014 – Version 5 


1 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
STUDY TITLE: 
Randomized, Double-Blind, Vehicle-Controlled Pilot Study 
of the Efficacy and Safety of HylaCare
TM in the Treatment 
of Acute Skin Changes in Patients Undergoing External 
Beam Radiotherapy for Tumors of the Breast. 
 
 
 
PROTOCOL NUMBER: 
 
STU 092012-058  
 
PRINCIPAL INVESTIGATOR: 
Asal Shoushtari Rahimi M.D., M.S.
  
University of Texas Southwestern Medical Center 
Department of Radiation Oncology 
 
CO Investigators: 
 
 
Ann Spangler MD 
Department of Radiation Oncology 
 
Dan Garwood MD 
Department of Radiation Oncology 
 
Marilyn Leitch MD 
Department of Surgery 
 
Roshni Rao MD 
Department of Surgery 
 
Barbara Haley MD 
Department of Medical Oncology 
 
Chul Ahn, PhD 
Professor 
Department of Clinical Sciences 
5323 Harry Hines Blvd 
Dallas, TX 75390-9066 
(214) 648-9418 
 
 
NUMBER OF PATIENTS TO 
BE TREATED: 
 
 
30 
 
 
 
 
 
 
ESTIMATED START DATE: 
 2013 
 
 
TEST ARTICLES:  
 
HylaCare
TM (Test Serum) 
 
 
 
 
 
Placebo (Control) 
Vehicle 
 
SPONSOR'S NAME AND 
ADDRESS: 
 
 
 
Hylaco, LLC 
 
 
 
 
 
3401 Lee Parkway Suite 1504 
 
 
 
 
 
Dallas, TX 75219 
 
: 
 
 
 
 
 
 
Version 
Date 
2 
March 6,2013 
3 
August 6, 2013 
 4 
 October 3, 2013 
 5 
 May 7, 2014 
 
 


2 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
This confidential information is provided to you as an investigat
or or potential investigator to be reviewed by you, your 
staff, and applicable institutional review board. It is understood
 that this information will not be disclosed to others 
without written authorization from Hylaco. 


3 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
TABLE OF CONTENTS  
 
1. INTRODUCTION AND PURPOSE 
 
2. BACKGROUND 
 
2.1 Study Objectives 
 
3. STUDY DESIGN 
 
4. STUDY PROCEDURES 
 
4.1 Subject Selection Criteria 
 
4.2 Study Duration 
 
4.3 Data Collection 
 
4.4 Concomitant Medication 
 
4.5 General Plan 
 
4.6 Test Article Blinding and Administration 
 
5. SOURCE OF RESEARCH MATERIAL 
5.1 HylaCare
TM and Vehicle Control 
5.2 Proper Handling and Storage 
 
6. EVALUATION AND CONSENT 
 
6.1 Baseline Procedures (Visit #BL) 
 
6.2 Table of Baseline and Subsequent Assessments 
 
6.3 Final Visit 
 
6.4 Informed Consent 
 
7. EFFICACY PARAMETERS 
 
8. POTENTIAL RISKS 
 
8.1 Definition of Adverse Events 
 
8.2 Severity of Adverse Events 
 
8.3 Steps to Determine if an Adverse Event Requires Expedited Reporting 
 
9. DATA MONITORING 
 
9.1 Statistical and Analytical Methods 
 
9.2 Subject Safety 
 
9.3 Monitoring Procedures 
 
9.4 Handling of Dropouts or Patients Lost to Follow-Up 
 
9.5 Discontinuation of Patients from Study 
 
10. PROCEDURES TO MAINTAIN CONFIDENTIALITY 
 
11. PROTOCOL ADMINISTRATION 
 
12.1 Discontinuation of Study 
 
12.2 Changes in Protocol 
 
12.3 Institutional Review Board 
 
12.4 Reporting of Data 
 
12.5 Final Report, Publication, and Protection of Trade Secrets 
 
12. INVESTIGATOR AGREEMENT 
 
13. REFERENCES 


4 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
1. INTRODUCTION AND PURPOSE 
More than 50% of all patients with cancer receive some form of radiotherapy (RT), for curative or 
palliative purposes, during the course of their illness. 
 
One of the dose-limiting effects of radiotherapy 
is the acute reaction that ionizing radiation 
induces in normal tissues. The severity of 
adverse events resulting from exposure to 
radiotherapy is, in general, related to age and general health as well as to treatment-related 
factors such as the area being treated, radiation dose per fraction, and the total dose 
administered. 
Skin toxicity is the most common acute side effect of radiotherapy to the breast, occurring in more 
than 90% of patients. (1)
 
 
The specific purpose of this trial is to determine whether the hyaluronan components of 
HylaCareTM induce an effectiveness response significantly greater than use of a vehicle control 
which lacks those ingredients in the management of acute skin reactions to external beam 
radiotherapy. 
 
2. BACKGROUND 
Early-onset adverse events occur to tissues soon
 after treatment initiationwith external beam 
radiation therapybegins. The emergence of such 
symptoms, when severe, can adversely affect 
the patient's quality of life, result in treatment interruptions, and can reduce patient compliance 
with the treatment regimen. Among the most common of these is skin toxicity, observed 
frequently in patients being treated for breast cancer. The onset of acute radio-epidermititis 
results in erythema, epilation, and epidermolysis, with the skin in the treated area becoming dry, 
pruritic, hypersensitive, easily irritated, and in the longer term, hyper-pigmented. With some 
forms of radiotherapy, treated skin may develop a mo
ist reaction, resulting in severe soreness in 
the area of body folds. In addition, patients 
treated for breast tumors may develop changes in 
skin texture. Most skin reactions resolve within a few weeks after treatment is completed, 
although the skin may remain slightly darker than pretreatment. 
 
The present management of radiation-associated skin
 toxicity includes instructions for care of 
the affected areas and the use of skin care products which can combat symptoms, without 
inducing further skin irritation. 
 
Attention has recently been focused on the effe
cts of hyaluronan (HA) for the management of 
radio-epithelitis and acute skin reactions. Liguori 
et al. (2) reported the effects of hyaluronan 
serum when applied to skin surfaces affected by radiation to head and neck, breast, and pelvic 
tumors. Compared to a matching placebo serum, patients treated with the HA serum showed a 
significant postponement in the first signs of acute radio-epithelitis and a reduction in the 
severity of skin reactions. 
The present study will evaluate the effectiveness and safety of HylaCare
TM in the management 
of acute skin reactions to extern
al beam radiotherapy. HylaCare
TM contains the patented 
HylaSponge®System, composed of small and large molecular weight hyaluronan 
(hyaluronic acid) and polymerized HylaSponges of infinite molecular weight. Due to its 
structure and preparation, the HylaSponge
®System is designed to improve the controlled 
release and slow delivery of various ingredients. A Repeated Insult Patch Test (RIPT) with 
HylaCareTM in 30 volunteer subjects demonstrated no potential for eliciting either dermal 
irritation or sensitization (3). 


5 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
The major properties which make this biopolymer unique and valuable for skin care are: 
 
Its ability to be loaded with, and then slowly release, water and a variety of active 
ingredients 
 
Extremely high water retention 
 
The quality of acting as a “second skin”, which is hydrated, protective, and 
biocompatible 
HylaCareTM, formulated as a topical product, has super-hydrating properties. It contains skin 
moisturizers such as pure low and high molecular weight hyaluronan, the 
HylaSponge®System, and squalane. These characteristics make HylaCare
TM an excellent 
candidate for use in the skin care of patients who may develop acute skin toxicity associated 
with the use of external beam radiotherapy. 
 
 
2.1 Study Objectives 
The objective of this controlled study will be 
to determine the effectiveness and safety of 
HylaCareTM in the management of the symptoms of acute skin toxicity induced by exposure to 
external beam radiotherapy associated with the treatment of breast cancer. 
 
The primary measures of effectiveness will be: 
 
1. Physician's Follow-Up Evaluation: assessing signs and symptoms at each irradiated site at 
week 5 during RT and at 2 weeks post-treatment: 
2. Physician's Global Assessment: assessing each irradiated site at 5 weeks of RT prior to 
boost and at 2 weeks post-treatment 
A secondary measure of effectiveness will be: 
 The patient's independent and separate assessment of the tolerance to radiotherapy of each 
treated site at Week 5 of radiotherapy and at 2 weeks after its completion. 
An additional method of evaluation will be the Investigator’s assessment (disease oriented team 
to do assessment) of the baseline and treatment timeline photos. 
 
3. STUDY DESIGN 
This will be a randomized, double blind, vehicl
e-controlled evaluation of the effectiveness and 
safety of HylaCare
TM. The study will employ the patient as her own control, a commonly used 
method for the evaluation of topical dermatologic agents. Each patient will be randomized blindly 
as to whether  the study serum will be applied to the medial or lateral portion of the treated 
breast, using the nipple as the dividing line (see Figure 1. below). The product and placebo will 
also be applied to the contra-lateral breast in the same fashion, as a further control. The study 
drug and placebo will be applied three (3) times daily, 
but not within 4 hours prior to 
radiation treatment.  It is a well known fact that any cream or moisturizer that leaves a film on 
the breast prior to radiation treatment can cause a bolus effect which can increases surface dose 
to the breast worsening dermatitis. Thus, no topical agent should be applied to the breast 4 hours 
before radiation treatment. 
 
Patients will be allocated to the treatment using a randomized permuted block. There will be no 
stratification. Patients will be randomized to receive the investigational product to be applied to 
either the medial (inside) or lateral (outside) portion of the breast, a placebo product will be used 
on the other side. Patients and clinical investigators will be blinded to the treatment assignments. 
 


6 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
Patients will also complete a 
daily log, recording daily application times. At, or prior to, the 
first radiotherapy visit, the patient will be provided with 3 Set Bags containing sufficient 
materials for 3 weeks of treatment, or as needed. Patients will receive more Set Bags at 
Week 3 and Week 5, or as needed. Patients an
d investigators will not know which bottle of 
serum is study serum vs. placebo. The bottles will be labeled with an identifying code 
showing the subject’s initials plus a patient number, and another label indicating where the 
serum is to be applied (medial or lateral part of the breast). 
 
Medial (down the middle of the breast bone) 
 
 
 
↓ 
 
 
 
Lateral (on the side) 
 
Lateral (on the side) 
 
 
 
Figure 1. Diagram showing medial and lateral portions of breasts to be addressed. 
Applications three (3) times per day will continue throughout the course of radiotherapy and for 
24 weeks after its completion (end of study). On any treatment day, there will be an application 
of test and control products immediately after the radiotherapy. No application will be made 
within four (4) hours prior to radiotherapy. 
 
HylaCareTM and a matching (in appearance, consistency and odor) vehicle control product will 
be supplied in identically appearing opaque bottles 
and dispensed according to a randomized 
code list prepared by the Statistician. 
 
This pilot study will be initially conducted at one center with 30 patients undergoing standard 
fractionation external beam radiotherapy. 
 
Patients enrolled in this study will be those who are to undergo curative or palliative 
radiotherapy for tumors of the breast. Treatment prescription will be 50.4 Gy in 28 fractions with 
tangential beams, followed by a 10 Gy in 5 fr
action electron or photon boost. Those who meet all 
selection criteria will have a history taken, 
undergo a physical examination, and a baseline 
evaluation by the Investigator . This evaluation will describe the tumor location and symptoms, 
as well as the intended radiotherapy treatment plan, dose, and duration of treatment. The 
radiation treatment protocol for each patient will be determined by the Radiation Oncologist. 
 
After the commencement of radiotherapy, patients will be evaluated at Week 5, and at 
2 weeks post-treatment, by one of the radiation oncology investigators who will examine 
and grade the breast for acute skin toxicity changes using the NCIC-CTC version 4.0 scale. A 
second Investigator Grading Scale will also be used for evaluation. Evaluation of the
 changes will 
also include examination and questioning for eryt
hema, pruritis, pain, dryness, exfoliation, 
epilation, hyperesthesia, or other signs/symptoms at each site. A supra-clavicular field may 
be irradiated and may also be treated with Products A and B, but will not be assessed for 
dermatitis. 
 
At study completion, both the Investigator and patient will, independently and separately, 
assess the overall dermatitis of the irradiated breast and the contralateral (non-irradiated) 
breast. 


7 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
1.  Grading Scale: NCIC-CTC 
Adverse Event 
1 
2 
3
4
5 
Dermatitis radiation 
Faint erythema or 
dry desquamation 
Moderate to brisk 
erythema; 
desquamation 
patchy moist 
desquamation, 
mostly confined to 
skin folds and 
creases moderate 
edema 
 
Moist desquamation 
in areas other than 
skin folds and 
creases  
bleeding induced by 
minor trauma or 
abrasion 
Life-threatening 
consequences; skin 
necrosis or 
ulceration of full 
thickness dermis; 
spontaneous 
bleeding from 
involved site; skin 
graft indicated 
Death 
Definition: A finding of cutaneous inflammatory reaction occurring as a result of exposure to biologically effective levels of ionizing
 
 
2.  Investigator Grading Scale: 
 
Grade the status of the medial and lateral sides of the irradiated skin as: 
0 = normal skin 
1 = light epidermal irritation, consisting of the onset of erythema, possibly associated with slight 
edema 
2 = erythema with dry desquamation 
3 = wet desquamation </= 2 cm 
4 = wet desquamation from 2.1 – 5cm 
5 = wet desquamation from 5.1 - 9 cm 
6 = wet desquamation > 9.1 cm 
 
4. STUDY PROCEDURES 
 
4.1 Subject Selection Criteria 
Patients will be recruited by the Investigator from his/her available patient population, or by 
referral. Selected patients must meet the Inclusion and Exclusion criteria: 
 
Inclusion Criteria 
 
Female, age 18 or older 
 
Diagnosis of breast cancer 
 
Intact breast (not surgically absent) 
 
Planned fractionated external beam radiotherapy to be delivered by opposing, 
tangential beams to 50.4 Gy in 28 fractions with a planned photon or electron boost 
of 10Gy in 5 fractions (for a total of 33 fractions) 
 
Ability to understand and comply with the requirements of this study 
 
Ability to give Informed Consent 
 
For sexually active females, patient agrees to use acceptable method of 
birth control 
 
Exclusion Criteria 
 
 
Women who are pregnant or lactating
 
 
Use of concomitant skin care preparations at any of the treated or control portal areas 
to be observed  
 
Any infection or unhealed wound of the radiotherapy portal areas, or generalized 
dermatitis 
 
Severe renal failure (serum creatinine 
> 3.0mg/dL) within 6 months of study 
registration 


8 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
Allergic history, including anaphylaxis or severe allergies to products in study serum 
or placebo 
 
Planned relocation which would make follow-up visits impossible during the course of 
the study  
 
Collagen vascular disease such as Lupus, or scleroderma
 
 
4.2 Study Duration 
Patients selected for this study will be undergoing radiotherapy for curative or palliative treatment 
with fractionated external beam radiotherapy 
to be delivered by opposing, tangential beams to 
50.4 Gy in 28 fractions with a planned photon or electron boost of 10 Gy in 5 fractions (total of 
33 fractions). Patients will be followed for 2weeks after radiotherapy has finished, with a follow- 
up visits at 2 weeks post-treatment. 
 
 
 4.3 Data Collection 
Data will be collected (typewritten, or handwritten legibly in black ink) on the appropriate case 
report forms supplied by the Sponsor. 
 
 
4.4 Concomitant Medications 
 
Patients will be asked about changes in their medications (prescription, nonprescription, or 
herbals) during their participation including name of the drug, indication for use, dosage, date 
started and date stopped. Changes in medications will be recorded. 
 
4.5 General Plan 
 
The patient's overall treatment plan will be guided by her tumor type. In general, its planning 
steps will include: 
 
1. Special radiologic studies may be ordered to help plan the radiation treatments 
2. Devices (e.g., breast boards, vac lok) may be fabricated to maintain proper 
positioning during treatment 
per the radiation oncologist 
3. Simulation x-rays will be performed to 
ensure accurate planning of the size and 
direction of the radiation treatment fields on a weekly basis 
4. Tattoos or other markers will be applied to ensure the proper setup for daily treatment 
5. Custom-made blocks may be fabricated, based on CT simulation, to shield normal 
structures 
6. During a setup session, the field ar
rangements and blocks will be checked for proper 
alignment 
7. In general, the borders of the field are: 
i. Superior: inferior to the clavicle 
ii. Lateral: mid-axillary line 
iii. Inferior: 2 cm inferior to the infra-mammary fold 
iv. Medial: Mid-sternum 
 
4.6 Test Article Blinding and Administration 
 
 At, or prior to, the first radiotherapy visit, the 
patient will be provided with 3 Set Bags containing 
sufficient materials for 3 weeks of treatment, or as needed. Patients will receive more Set Bags 
at Week 3 and Week 5, or as needed. Each Set Bag will contain two (2) 60 mL bottles of 
HylaCareTM, and two (2) i
dentically appearing bottles of Placebo (Control Vehicle). Both 
containers will be labeled with the patient's initials , study number, and location of skin to be 
covered (ie. right lateral breast, left medial breast, etc.) Additionally, the patient will be 
instructed as to the proper application of the serums, including amount, location, coverage, 


9 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
and hand washing. 
See “Patient Instructions”, Form 8 
The contents of each bottle (HylaCare
TM or Placebo) will have been determined by a 
computerized random assignment scheme, the code fo
r which will be kept at the study site in a 
sealed envelope. 
 
The radiotherapy nurse, research team or physician will instruct the patient as to the proper 
application method and ensure that the patient understands which container contents are to be 
applied to which site (see Figure 1 and Patient Instructions, Form 8). The patient will apply a 
sufficient amount of either HylaCare or plac
ebo (as prescribed in the experimental randomized 
design) to cover the entire marked surface of their irradiated skin area IMMEDIATELY AT THE 
END OF THE TREATMENT SESSION. At this time the same treatment will be applied to the 
contralateral (non-irradiated) breast. The patient will make two other applications during the day 
to ensure a total of three (3) daily applications of both HylaCare
TM and the vehicle control. 
No 
applications will be made within 4 hours before radiotherapy. 
 The three (3) daily 
applications will continue throughout the course of radiotherapy and for 2 weeks after 
its completion. A drawn dashed line on both treated and untreated breast, as seen in Figure 
1 will determine areas for use of study serum and placebo. 
 
The patient will also be instructed: 
1. To apply product only to the areas identified on both breasts 
immediately after the 
radiotherapy session, and then two more times that day. 
2. On non-treatment days, to apply the product three (3) times daily 
3. Not to use other skin care products on any of the radiotherapy-exposed skin areas 
4. To report any generalized reactions or any localized reactions in treatment area to the 
investigator at the next daily session, or more severe reactions by telephone (See 
Section 8). 
5. to discontinue use of topical agents if they develop >/= grade 3 dermatitis. 
 
 
Suggestions for personal care of the irradiated treatment sites may include: 
 
1. Avoid irritating the skin 
2. When washing, use only lukewarm water and mild soap, patting the surface 
dry 
3. Avoid the use of tight clothing 
4. Do not rub, scrub or scratch the skin 
5. Avoid the use of heating pads or ice packs 
6. Do not use powders, creams, perfumes, deod
orants, body oils, ointments, or lotions 
on the irradiated surfaces 
7. Avoid direct sun exposure; if necessary, wear protective clothing 
 
5. SOURCE OF RESEARCH MATERIAL 
 
5.1 HylaCareTM (Test Serum)and Place
bo (Vehicle Control) 
HylaCareTM (Test Serum)and Placebo (Vehicle Control) will be supplied in identically appearing 
opaque 60 mL bottles. 
 
HylaCareTM contains the following ingredients: 
HylaSponge®System 
 Water 
Xanthan gum 
Hydroxyethylcellulose 


10 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
Squalane 
EMT Polymer (Hydroxyethyl acrylate, Sodium acryloyldimethyl, Taurate copolymer) 
Benzylalcohol-DHA (benzylalcohol, (dihydroacetic acid) 
 
The Vehicle Control contains the above-
noted ingredients except for HylaSponge
®System 
 
5.2 Proper Handling and Storage 
1. Store test article containers at room temperature 
2. Do not freeze 
 
6. EVALUATIONS AND CONSENT 
Patients who meet all selection criteria will 
be enrolled in numerical 
sequence.  The assigned 
number will correspond to the order in which they are enrolled. The following visits will occur: 
Visit # 
Title 
Time 
 BL* 
Baseline Evaluation(s) 
0 (Prior to treatment) or Week 1 visit 
1 
Radiotherapy (RT) 
Initiation 
2 
Follow-Up Evaluation 
At 5 Weeks prior to boost 
3 
Final Evaluation 
 2 weeks after RT ends 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Baseline Evaluation may require more than one visit. 
 
6.1 Baseline Procedures (Visit #BL) 
 
At the Baseline Evaluation, all enrolled patients will undergo history, physical 
examination, and baseline laboratory/radi
ological assessments dictated by the 
plan of treatment for the tumor to undergo radiotherapy. 
 
The Research Team or treating Physician will complete these forms and actions: 
 (Form 1) Informed Consent (Form 1) 
 (Form 2a/2b) Inclusion /Exclusion Criteria (Forms 2A/2B) 
 (Form 3) Physician Follow-Up Assessment Form 3 
 (Form 4) Demographics and History Form 4 
 (Form 5) General Physical Examination Form 5 
  (Form 6) Radiotherapy Treatment 
 (Form 7) Patient Daily Log 
 (Form 8) Patient Instructions 
 
6.2 Table of Baseline and Subsequent Assessments 
Assessment of all radiation-exposed skin areas will occur as directec in the table below 
following the initiation of radiotherapy and at 2 and 4 weeks after the completion of radiotherapy. 
These forms and activities will be completed or reviewed at each assessment: 
 


11 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
FORM / ACTION 
 
Base 
Line 
 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Week 
5 
Prior to 
boost 
Week 
6 
 
Week 
 7 
2 
weeks 
post 
Informed Consent 
ⱱ 
 
 
 
 
 
 
 
 
Photography 
ⱱ 
 
 
 
 
ⱱ 
 
 
ⱱ 
Inclusion/ 
Exclusion Criteria 
ⱱ 
 
 
 
 
 
 
 
 
Physician Follow-
Up Assessment 
 
 
 
 
 
ⱱ** 
 
 
ⱱ 
Demographics 
and History 
ⱱ 
 
 
 
 
 
 
 
 
General Physical 
Examination 
ⱱ 
 
 
 
 
 
 
 
 
Concomitant 
Medication 
ⱱ 
review 
review 
review 
review 
review 
review 
review 
review 
Baseline 
Assessment 
ⱱ 
 
 
 
 
 
 
 
 
Urine Pregnancy 
Test 
ⱱ*** 
 
 
 
 
 
 
 
 
Radiotherapy 
Treatment 
 
**** 
 
 
 
 
 
 
 
Patient Daily Log 
 
ⱱ 
ⱱ 
ⱱ 
collect 
log 
page
ⱱ 
ⱱ 
collect 
log page  
ⱱ 
ⱱ 
ⱱ 
collect 
log page  
Adverse Event 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If needed  
Patient Overall 
Evaluation 
 
 
 
 
 
ⱱ*****
 
 
ⱱ 
Physician Global 
Assessment 
 
 
 
 
 
ⱱ 
 
 
ⱱ 
Patient 
Completion 
 
 
 
 
 
 
 
 
ⱱ 
 
* Photographs of patient’s breasts prior to radiation therapy: The baseline photo should be a 
close-up encompassing only the breast to be treated at a 45 degree oblique angle with arms 
elevated over the patient’s head. Other photos should be a straight frontal view of both breasts 
taken in either a standing or seated position with the patient’s hands on her hips, excluding her 
face. Boost area will be labeled prior to week 5 photo and a photo will be taken showing the boost 
area.  Label each slide or photograph with the date and the patient case number. The labeled 
photographs will be stored electronically under study specific patient folders. 
 
** Separate photo with boost drawn on skin. 
*** If Patient is of child-bear
ing age and sexually active 
**** Prior to first Radiation Therapy 
 
***** Evaluation should be completed prior to boo
st, but Patient will not be removed from the 
study is this is completed after the boost. 
 
 
6.3 Final Visit 
This will occur at 2weeks after the completion of radiotherapy. These forms and actions will be 
completed: 
 
Physician’s Follow-Up Assessment Form 3 
Describes the radiotherapy treatment and provides a time line to compare 
irradiated and non-irradiated breast indications 
 
Physician's Global Assessment Form 9 


12 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
To be completed at Week 5 prior to boost and also 2 weeks post radiation 
 
Patient Overall Evaluation Form 10 
 Used to elicit patient evaluation of prophylaxis 
 
Patient Completion Form 11 
Final compilation of patient data upon study completion or discontinuation 
 
6.4 Informed Consent  
Written consent will be obtained from each patient prior to entering this trial and will become 
part of the patient’s permanent study record. Each patient will be assured that study 
participation is voluntary and that she may withdraw at any time. At the time of obtaining 
written consent, the Investigator will advise patients of the experimental nature of HylaCare
TM, 
the duration of the trial, alternate modes of prophylaxis, and prevalent adverse events that 
might occur and discuss willing
ness to have photographs taken.
 
 
7. EFFICACY PARAMETERS 
The primary measures of effectiveness will be: 
 
Physician's Follow-Up Evaluation(Form 3): assessing signs and symptoms at each 
irradiated site Week 5 during RT and at 2 weeks post-treatment 
 
Physician's Global Assessment: assessing each irradiated site at Week 5 RT prior to boost 
and at2 weeks post-treatment 
A secondary measure of effectiveness will be the patient's independent and separate assessment 
of the tolerance to radiotherapy of each treated site at the completion of radiotherapy and at 2 
weeks after its completion. 
An additional method of evaluation will be the Investigator’s assessment (disease oriented team 
to do assessment) of the baseline and timeline photos.
 
 
In addition, other local (irradiated areas) symptoms/signs (e.g., pain, tenderness, pruritus, 
dryness, epilation, hyperesthesia) and any gene
ralized adverse events will be evaluated on the 
basis of NCIC toxicity criteria 
http://ctep.cancer.gov/reporting/ctc.html . 
 
Week 5 of radiotherapy and at the 
final evaluation (2 weeks post-treatment), the Investigator will 
make an overall global assessment of effectiveness of radiation tolerance of the treated breast 
(medial and lateral breast will be scored individua
lly). This assessment will be based upon the 
Investigator’s experience, comparing the skin appearance and symptomatology of the site with 
the normally expected degree of radiation damage for similar body sites. The overall result will 
be graded as: 
 
0= poor  (worse than typical expectations) 
1= fair (equal to, or slightly better than typical expectations) 
2= good (moderately better than typical expectations) 
3= excellent (markedly better than typical expectations) 
 
The Investigator will also judge which of the paired sites (medial, lateral) ) tolerated 
radiotherapy better, in terms of: (1) symptoms experienced by the patient and (2) overall skin 
appearance. If investigator feels medial and lateral breast symptomatology equivalent, then 
this will be reported as such. 
 
Independent of the Investigator, the patient will also assess which of the paired sites fared 
better in terms of: (1) symptoms experienced and (2) overall skin appearance, at the completion 
of radiotherapy and 2 weeks post-treatment. 


13 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
8.   Potential Risks 
Investigational Product: 
In previous use of HylaCare as a commercial product, no adverse events have been 
identified. 
 
Psychological Stress: 
Questionnaires will be given to the patient as a part of this study, which may make them feel 
uncomfortable. Patient can refuse to answer any of the questions, take a break or stop 
participating in this study at any time. 
 
Loss of Confidentiality: 
Any time information is collected; there is a potential risk for loss of confidentiality. Every 
effort will be made to keep the patients information confidential; however, this cannot be 
guaranteed. 
 
Photographs: 
Patient could feel slightly uncomfortable during the photographic sessions when asked to 
position the body to take the photograph of the breast area. Patients could be uncomfortable 
with standing still for an extended period of time or from turning their body in various 
positions. They could be sensitive to the bright and repeating flashes from the camera, which 
can sometimes cause headaches, irritation of the eyes, discomfort, after effects such as 
seeing spots, and in rare cases, could stimulate a migraine headache or epileptic seizure. 
 
Photographs include a risk of identification. Patients privacy will be protected to the greatest 
extent possible. Photos will be taken to exclude faces or any other identifying marks. Photos 
will only be identified by a unique subject identification number that contains no personal 
identifying information. For research purposes, photos may be used in scientific publications. 
 
Risks to Embryo, Fetus or Breast-fed Infant: 
Females: For patients who are pregnant or breast-feeding an infant, it is possible that they 
may expose the unborn child or infant to risks. 
 For that reason, pregnant and breast-feeding 
females cannot participate in the study. For patient who are participating in this study and 
are of childbearing age and sexually active, results of a urine pregnancy test will be 
obtained, and it must be negative before participating in the study. Patient taking part in this 
study and who are sexually active, must use medically-acceptable birth control 
(contraceptives) during the study. Medically-acceptable birth control (contraceptives) 
includes: 
(1) Surgical sterilization (such as
 hysterectomy or “tubes tied”), 
(2) Approved hormonal contraceptives ( such as birth control pills, patch or ring; Depo-
Provera, Depo-Lupron, Implanon), 
(3) Barrier methods (such as condom or diaphragm) used with a spermicide (a substance 
that kills sperm), or 
(4) An intrauterine device (IUD). 
Patient who become pregnant during this study, must notify the researchers immediately. 
 
Other Risks 
There may possibly be other side effects that are unknown at this time. 
 
Radiation exposure to a woman’s reproductive organs may harm an embryo or fetus. Also, if 
radioactive materials are used for certain types of scans, harm may come to an embryo, 
fetus, or an infant who is breast feeding. 
 


14 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
Pregnancy tests performed during the early stages of pregnancy do not always reveal 
pregnancy. Therefore, radiation exposure that includes the reproductive organs will be 
limited to the first ten days after a woman who can become pregnant has begun her most 
recent menstrual period. This is standard policy in clinics and hospitals within UT 
Southwestern. This policy applies unless there is an important medical reason requiring 
radiation outside this time frame. 
 
Risks of Radiation – Radiation Therapy : 
The radiation therapy used in this research is the standard radiation therapy, therefore, the 
risk of harm involved is the same. 
 
High-dose radiation treatments to or near a man’s testicles or a woman’s ovaries may 
produce harmful changes that could be passed on to children through a sperm or an egg. 
 
Women: Females able to have children should avoid becoming pregnant until after they 
have had three menstrual periods after the end of all radiation therapy. After three 
menstrual periods, there is almost no risk of harmful changes to an egg. 
 
Possible side effects of radiation therapy to the breast include: 
 
Likely (these side effects occur in 10% or more of patients): 
 
Reddening of the skin during treatment and for several weeks following 
treatment 
 
Tanning of the skin lasting months and may be permanent 
 
Slightly smaller breast size or change in the way the breast looks 
 
Tiredness and weakness during treatment and for several weeks following 
treatment 
 
Swelling of the breast 
 
Peeling of the skin in the area treated with radiation 
 
Mild pain at the site of radiation treatment requiring over the counter pain 
Relievers. 
 
Less Likely (these side effects occur in 3-9% of patients): 
 
Soreness or tightness in muscles of the chest wall under the treated 
breast 
 
Severe pain at the site of radiation requiring prescription pain relievers 
 
Rare but Serious (these side effects occur in less than 3% of patients): 
 
Cough 
 
Difficulty breathing 
 
Inflammation of the heart muscle 
 
Rib fracture 
 
Slight increase in risk for heart disease for patients with cancer in the leftbreast 
 
Risk of developing another cancer  
 
At each follow-up assessment, patients will be evaluated for any adverse effects. These will be 
grouped as follows: 
 
1. Localized reactions at the irradiated sites 
 
2. Other adverse events 
 
The Investigator will enter details of any of these events on the Adverse Event Form. The 


15 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
duration, intensity, and any action taken will be recorded. 
 
8.1 Definition of Adverse Event 
An adverse event (AE) is any untoward medical o
ccurrence in a patient receiving study treatment 
and which does not necessarily have a causal relationship with this treatment. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of an experimental intervention, whether 
or not related to the intervention. 
8.2 Severity of Adverse Events 
All non-hematologic adverse events will be graded 
according to the NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0. The CTCAE v4 is available at 
http://ctep.cancer.gov/reporting/ctc.html 
 
If no CTCAE grading is available, the severity of an AE is graded as follows: 
Mild (grade 1): the event causes discomfort without disruption of normal daily activities. 
Moderate (grade 2): the event causes discomfort that affects normal daily activities. 
Severe (grade 3): the event makes the patient unable to perform normal daily activities or 
significantly affects his/her clinical status. 
Life-threatening (grade 4): the patient was at risk of death at the time of the event. 
Fatal (grade 5): the event caused death. 
8.3 Steps to Determine If an Adverse Event Requires Expedited Reporting 
Step 1: Identify the type of adverse event using the NCI Common Terminology 
Criteria for Adverse Events (CTCAE v4). 
 
Step 2: Grade the adverse event using the NCI CTCAE v4. 
 
Step 3: Determine whether the adverse event is related to the protocol therapy 
Attribution categories are as follows: 
- 
Definite – The AE 
is clearly related to the study treatment. 
- 
Probable – The AE is likely related to the study treatment. 
- 
Possible – The AE 
may be related to the study treatment. 
- 
Unrelated – The AE 
is clearly NOT related to the study treatment. 
Note: This includes all events that occur within 30 days of the last dose of protocol 
treatment. Any event that occurs more than 30 days after the last dose of 
treatment and is attributed (possibly, probably, or definitely) to the agent(s) must 
also be reported accordingly. 
 
Step 4: Determine the prior experience of the adverse event. 
Expected events are those that have been prev
iously identified as resulting from 
administration of the agent. An adverse
 event is considered unexpected, for 
expedited reporting purposes only, when either the type of event or the severity of 
the event is not listed in: 
 
the current known adverse events 
listed in the Agent Information 
Section of this protocol; 
 
the drug package insert; 
 
the current Investigator’s Brochure 
 
The intensity of adverse events will be graded as mild, moderate, or severe to describe 


16 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
these observations regardless of whether they are medical events, symptoms, or physical 
findings. For purposes of consistency, the following definitions of intensity are provided: 
 
Mild: 
Easily tolerated, causes minimal discomfort and does not interfere 
with everyday activities 
Moderate: 
Causes sufficient discomfort to interfere with normal 
everyday activities 
Severe: 
Incapacitating and prevents normal everyday activities 
 
A Serious Adverse Event is
 any experience that suggests a significant hazard, contraindication, 
side effect or precaution, and includes any experience which: 
 
is fatal or life-threatening 
 
is permanently disabling (i.e., incapacitating or interfering with the ability to resume 
usual life patterns 
 
requires in-patient hospitalization or prolongation of hospitalization 
 
is a secondary cancer, or an overdose 
For HylaCare TM, potential adverse events might include an allergic reaction. Although this has 
not been observed in other clinical trials of 
hyaluronan-based agents, this product is hyaluronan 
derived from a biological source; hence, the Investigator should be aware of the possibility that 
the material theoretically could cause an allergic reaction. 
 
Any Serious Adverse Event Form should be faxe
d, then emailed immediately to Hylaco 
(Janet L. Denlinger PhD, Chief Scientific Officer 201 886 1643/jdenlinger@hylaco.com) and 
Jean Wu (214-645-8913/jean.wu@utsouthwestern.edu). Any death or serious or unusual 
reaction is to be reported promptly (within 24 hours) by telephone to Dr. Denlinger (201 886 1562) 
or, in her absence, to Morgan Hare (214 559 
6125) , even though it may not appear to be related 
to HylaCare TM. 
All adverse events will be reviewed at the monthly radiation oncology research meeting which 
includes radiation oncologist not adhering to the protocol. 
 
Any preliminary telephone report of a serious 
adverse event is to be followed by a detailed 
written report summary within three working days and must include copies of hospital/office 
records and other documents when applicable. An additional follow-up written report summary is
 
to be forwarded to Hylaco within 10 days of the 
adverse event. The Investigator will also notify 
his/her Institutional Review Board (IRB) of any deaths, serious or unexpected reactions. 
 
Follow-up of all adverse events will be continu
ed until the overall clinical outcome has been 
ascertained. All deaths, serious and non-serious adverse events will be summarized in the 
report prepared for Hylaco after the conclusion of the study. 
 
UTSW IRB: SAEs will be collected from the time consent is given, throughout the 
treatment period, and until subject’s participation in the trial has ended or participants 
death. 
Investigators and other site personnel must inform the UTSW IRB, of any serious 
or unexpected adverse events that occur in accordance with the reporting 
obligations of 21 CFR 312.32, and will concurrently forward all such reports to 
UTSW IRB. It is the responsibility of the investigator to compile all necessary 
information. 


17 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
If a non-serious AE becomes serious, this and other relevant follow-up information 
must also be provided to UTSW IRB.. 
 
All SAEs have to be reported to UTSW IRB, whether or not considered causally 
related to the investigational product.  All SAEs will be documented.  The 
investigator is responsible for informing the IRB and/or the Regulatory Authority of 
the SAE as per local requirements. 
 
Non-serious adverse events will be collected
 from the time consent is given, 
throughout the treatment period and up to and including the 
30 day follow-up 
period.   After withdrawal from treatment, subjects must be followed-up for all 
existing and new AEs for 30 calendar days after the last dose of trial drug and/or 
until event resolution. All new AEs occurring during that period must be recorded 
(if SAEs they must be reported to the UTSW IRB).  All study-related toxicities/ 
SAEs must be followed until resolution, unless in the Investigator’s opinion, the 
condition is unlikely to resolve due to the patient’s underlying disease. 
 
All serious adverse events must be reported to the
 UT Southwestern TELEPHONE 
LINE: (214) 633-1753 within 24 hours of the investigator’s awareness of the 
occurrence of the event. All safety reports shall be faxed to (214) 645-8913 or e-
mail to the attention of the project manager. 
 
The following events meet the definition of UPR: 
1. Any serious event (injuries, side effects, deaths or other problems), 
which in the opinion of the Principal Investigator was unanticipated, 
involved risk to subjects or others, and was possibly related to the 
research procedures. 
2. Any serious accidental or unintentional change to the IRB-approved 
protocol that alters the level of risk. 
3. Any deviation from the protocol taken without prior IRB review to 
eliminate apparent immediate hazard to a research subject. 
4. Any new information (e.g., publication, safety monitoring report, 
updated sponsor safety report), interim result or other finding that 
indicates an unexpected change to the risk/benefit ratio for the 
research. 
5. Any breach in confidentiality that may involve risk to the subject or 
others. 
 
 
9. DATA MONITORING
 
 
9.1 Statistical and Analytical Methods 
 
Thirty patients will be recruited in this pilot st
udy. Descriptive statistics will be computed 
to estimate the sample size needed for a future larger study if the study results looks 
promising. 
 
Descriptive statistics will be obtained for baseline demographic, medical history, 


18 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
physical examination, radiation therapy treatment/dosimetry data. 
Patients will be allocated to the treatment using a randomized permuted block. There will be no 
stratification. Patients will be randomized to receive the investigational product to be applied to 
either the medial (inside) or lateral (outside) portion of the breast, a placebo product will be used 
on the other side. Patients and clinical investigators will be blinded to the treatment assignments. 
The primary efficacy variables are the Physici
an's Follow-Up Evaluation, to be performed at 
each visit, and the Physician's Global Assessment, to be performed at the end of radiotherapy 
and 2 (two) weeks after the completion of radiotherapy. The 
key component of the Physician's 
Follow-Up Evaluation is the grading, on an ordinal scale (0 to 5) NCIC-CTC, as well as the 
Investigator Grading Scale of the irradiated area of the breast. The data collected from the 
Physician's Follow-Up Evaluation will be grouped into two parts, those data collected during 
radiotherapy and those data collected following the completion of radiotherapy. For each 
patient, the difference between the HylaCare
TM treated side and the control side will be 
determined at each visit during radiotherapy. These differences will then be averaged for each 
patient. The significance of the mean difference among the patients will then be determined 
using a paired t-test or Wilcox
on signed-rank test. The data obta
ined during the period following 
radiotherapy will be analyzed in this manner. The analysis of the Physician's Global 
Assessment will also be performed separately at the completion of radiotherapy and at the end 
of the follow-up period. The comparison of the groups will be based on a paired t-test or 
Wilcoxon signed-rank test. A secondary analysis will be performed to examine the possible 
influence of body habitus (BMI- breast size) and radi
ation hot spots on the effectiveness of the 
HylaCareTM prophylaxis. All efficacy analyses will be based on a modified intent-to-treat patient 
population. This population will be defined as 
all patients who commence radiotherapy and who 
have at least one on-treatment visit. 
 
The secondary efficacy measure is the patient's
 assessment of the tolerance to radiotherapy. 
These data will be collected at the end of radiotherapy and at the end of the follow-up period. At 
each time point the patient will be asked three questions and will respond to each question by 
indicating which product was preferred or if the patient had no preference. For each question the 
analysis will compare, among those patients who have a preference, the percent who prefer 
HylaCareTM to the percent who prefer the control. The comparison will be based on an exact 
Binomial test of the hypothesis that the percent who prefer HylaCare
TM is 50%, the percent that 
corresponds to the patient having no preference between HylaCare
TM and the control. 
 
The evaluation of photos taken during the course 
of radiotherapy represents the third efficacy 
measure. These will be evaluated in a blinde
d manner by the disease 
oriented team (which 
may consist of breast surgeons, plastic surgeons, or medical oncologists) after the last patient 
completes post-treatment week 2 follow-up and photo 
 
Safety will be assessed through the recording of responses and other adverse events. All 
patients who undergo prophylaxis will be included in the analyses. The adverse events will be 
classified using the NCIC-CTC version 4.0. 
 All computations will be performed using Statistical Analysis System (SAS) software. 
 
 Grading NCIC-CTC 
Adverse Event 
1 
2 
3
4
5 
Dermatitis radiation 
Faint erythema or 
dry desquamation 
Moderate to brisk 
erythema; 
desquamation 
patchy moist 
desquamation, 
mostly confined to 
skin folds and 
creases moderate 
Moist desquamation 
in areas other than 
skin folds and 
creases  
bleeding induced by 
minor trauma or 
abrasion 
Life-threatening 
consequences; skin 
necrosis or 
ulceration of full 
thickness dermis; 
spontaneous 
bleeding from 
involved site; skin 
Death 


19 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
edema
 
graft indicated 
Definition: A finding of cutaneous inflammatory reaction occurring as a result of exposure to biologically effective levels of ionizing
 
 
Investigator Grading Scale: 
0 = normal skin 
1 = light epidermal irritation, consisting of the onset of erythema, possibly associated with slight 
edema 
2 = erythema with dry desquamation 
3 = wet desquamation </= 2 cm 
4 = wet desquamation from 2.1 -- 5 cm 
5 = wet desquamation from 5.1 - 9 cm 
6 = wet desquamation > 9.1 cm 
 
 
9.2 Subject Safety  
Safety will be assessed through the recording of responses and other adverse events. All 
patients who undergo prophylaxis will be included in the analyses. The adverse events will be 
classified using the NC
IC-CTC scale 4.0. 
 
 9.3 Monitoring Procedures  
Throughout the study, the monitor or a designated deputy will monitor completion of the forms, 
discuss questions regarding adverse events, remova
l of patients from the trial, study conduct, 
or the use of the test articles. 
 
The monitor will pay site visits to review each patient's Case Report Forms to help ensure 
completeness and accuracy of data entry specified 
in the Protocol. As required by Good Clinical 
Practices guidelines, clinical records will be reviewed to confirm that: (1) the case report forms 
are consistent with the Investigator's clinical records; (2) background clinical and laboratory data 
and concomitant medications are recorded on the 
case report forms; (3) there is an accurate 
account of test and control article use; and (4) there is timely, appropriate reporting of any 
adverse events. 
Patients will be instructed to
 discontinue use of topical agents if they develop >/= grade 3 
dermatitis. 
 
The data and safety Monitoring Board/Committee are: 
 Internal DSMB/DSMC 
 UTSW Radiation Onclolgy Investigators 
 External DSMB/DSMC 
 Simmons Cancer Center 
 
9.4 Handling of Dropouts or Patients Lost to Follow-Up 
All patients who meet the selection criteria will be considered evaluable for efficacy and safety. 
Every attempt will be made to ensure that all 
patients complete the required follow-up visits. 
Those not appearing will be telephoned and/or contacted by mail to ensure that they complete 
their visit schedule. The reason for all dropouts is to be specified by the Investigator on the 
Patient Completion Form.  
 
9.5 Discontinuation of Patients From Study 
Participation in this study may be discontinued for any of the following reasons: 
 
adverse events 
 
severe inter-current illness 


20 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
administrative reasons 
 
patient's voluntary decision to discontinue participation 
 
Investigator's opinion that it is not in the patient's best interests to continue 
 
Any patient discontinued because of an adverse event will be followed for at least 4 weeks, or 
until the adverse event is resolved, or as otherwis
e medically indicated. It is important that the 
reason and the date of discontinuation be reported on the Patient Completion Form. If at all 
possible, an assessment should be
 done at the time of withdrawal. 
Patients who failed to apply the test and control products  as directed for more than 5 days 
during radiation will be removed fr
om the study for noncompliance. 
 
 
10. PROCEDURES TO MAINTAIN CONFIDENTIALITY 
Confidentiality of each patient's identity will be maintained. A subject number consisting of the 
patient’s initials and a random number will be assigned to each patient upon study entry and that 
number will be used to identify that 
patient for the duration of the st
udy. Only the patient's initials 
and numbers will be used on case report forms as well as any study-related correspondence. 
 
 
11. PROTOCOL ADMINISTRATION 
 
11.1 Discontinuation of the Study 
 
Hylaco reserves the right to discontinue any study for administrative reasons at any time such 
as, but not limited to, a decision to discontinue further clinical investigation with the test article, 
improper conduct of the study by the Investigator, or inability to obtai
n the number of patients 
required by the Protocol. Reimbursements for re
asonable expenses will be made if such action 
is necessary. 
 
11.2 Changes in the Protocol 
Any changes that may affect the scientific soundness of the investigation or the rights, safety, 
or welfare of the subjects must receive appropri
ate IRB approval prior to implementation. Any 
changes in this Protocol will require the express written consent of Hylaco. 
 
11.3 Institutional Review Board 
Prior to implementation of this study, the Protocol and Patient Consent Form must be reviewed 
and approved by a properly constitut
ed Institutional Review  Board (IRB). No ch
anges that relate 
to the safety or welfare of patients may be made to the consent form unless they are approved by 
the IRB and Hylaco. All major amendments to the Protocol and case r
eport forms must also be 
approved by the IRB and by Hylaco. 
 
11.4  Reporting of Data 
All information required by the Protocol is to be provided, or an explanation given for omissions. 
All case report forms (CRFs) must be made available as soon as they are completed in order 
that the Study Monitor may verify the validity and completeness of those forms and permit 
transmittal of the data to the Sponsor. 
 
All data and information on these CRFs are to be neatly recorded in type or legibly written in 
black ink for ease of duplication, interpretation and analysis before submission to Hylaco. All 
corrections on the CRFs should be crossed out neatly with a single line, and the new entry 
initialed and dated by the member of the Investigator's staff making tile correction. Prior to 
forwarding the CRFs to Hylaco, they should be reviewed for completeness, accuracy, 
and legibility by the Principal Investigator and the Study Monitor. He/she will indicate by 


2 1 
1 4 0 5 0 7 H yla Care 
R a n d o miz e d, D o u bl e- Bli n d, V e hi cl e C o ntr oll e d Pil ot St u d y of t h e Effi c a c y a n d S af et y of H yl a C ar e T M    i n t h e Pr o p h yl a xi s of A c ut e S ki n 
C h a n g e s i n P ati e nt s U n d er g oi n g E xt er n al B e a m R a di ot h er a p y f or  T u m or s of t h e Br e a st  
si g n at ur e o n t h e a p pr o pri at e f or m s t h at h e/ s h e h a s r e vi e w e d t h e d at a at e a c h e v al u ati o n p eri o d. 
 
 
1 2. 0 R E F E R E N C E S 
( 1) R ef er e n c e: T o pi c al H y al ur o ni c A ci d v s. St a n d ar d of C ar e f or t h e Pr e v e nti o n of R a di ati o n 
D er m atiti s Aft er A dj u v a nt R a di ot h er a p y f or Br e a st C a n c er: Si n gl e- Bli n d R a n d o mi z e d 
P h a s e III Cli ni c al Tri al . I nt er n ati o n al J o ur n al of R a di ati o n O n c ol o g y* Bi ol o g y* P h y si c s 
V ol u m e 8 3, I s s u e 4, 1 5 J ul y 2 0 1 2, P a g e s 1 0 8 9 – 1 0 9 4    C h el s e a Pi n ni x, M. D., P h. D. , G e or g e H. 
P er ki n s, M. D., M. P. H. ,  Eri c A. Str o m, M. D. , W e n d y W o o d w ar d, M. D., P h. D. ,  
 
( 2) Li g u ori, V., G uill e mi n, C., P e s c e, G. F., Miri m a n off, R. O., a n d B er ni er, J. ( 1 9 9 7). D o u bl e-
bli n d, r a n d o mi z e d cli ni c al st u d y c o m p ari n g h y al ur o ni c a ci d cr e a m t o pl a c e b o i n p ati e nt s tr e at e d 
wit h r a di ot h er a p y. R a di ot h er a p y a n d O n c ol o g y 4 2, 1 5 5- 1 6 1.  
 
( 3) Fi n al R e p ort: R e p e at e d I n s ult P at c h T e st f or H yl a C ar eT M  B at c h c o d e l ot # 3 4 9 0 5 R 0 2 0 7 1 1. 
L a b a n d 2- 7- 1 1. 
 
 
 
 
 
 
 
A P P E N DI X A 
 
E V A L U A TI O N S a n d  A C TI O N S  


22 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
Baseline Visit 
At the Baseline Evaluation, all enrolled patients will undergo history, physical 
examination, and baseline laboratory/radi
ological assessments dictated by the 
plan of treatment for the tumor to undergo radiotherapy. 
The Research Team or treating Physician will complete these forms and actions: 
 
(Form 1) Informed Consent 
 
(Form 2a/2b) Inclusion /Exclusion Criteria 
 
(Form 3) Physician Follow-Up Assessment 
 
(Form 4) Demographics and History 
 
(Form 5) General Physical Examination 
 
 ((Form 6) Radiotherapy Treatment 
 
(Form 7) Patient Daily Log 
 
(Form 8) Patient Instructions 
 
6.2 Table of Baseline and Subsequent Assessments 
Assessment of all radiation-exposed skin areas will occur as described in the table below 
following the initiation of radiotherapy and at 2  weeks after the completion of radiotherapy. 
These forms and activities will be completed or reviewed at each assessment: 
 
 
FORM / ACTION 
 
Base 
Line 
 
Week 
1 
Week 
2 
Week 
3 
Week 
4 
Week 
5 
Prior 
to 
boost 
Week 
6 
 
Week 
 7 
2 
weeks 
post 
Informed Consent 
ⱱ 
 
 
 
 
 
 
 
 
Photography 
ⱱ 
 
 
 
 
ⱱ 
 
 
ⱱ 
Inclusion/ 
Exclusion Criteria 
ⱱ 
 
 
 
 
 
 
 
 
Physician Follow-
Up Assessment 
 
 
 
 
 
ⱱ** 
 
 
ⱱ 
Demographics 
and History 
ⱱ 
 
 
 
 
 
 
 
 
General Physical 
Examination 
ⱱ 
 
 
 
 
 
 
 
 
Concomitant 
Medication 
ⱱ 
review 
review 
review 
review 
review 
review 
review 
review 
Baseline 
Assessment 
ⱱ 
 
 
 
 
 
 
 
 
Urine Pregnancy 
Test 
ⱱ*** 
 
 
 
 
 
 
 
 
Radiotherapy 
Treatment 
 
**** 
 
 
 
 
 
 
 
Patient Daily Log 
 
ⱱ 
ⱱ 
ⱱ 
collect 
log 
page
ⱱ 
ⱱ 
collect 
log 
page
ⱱ 
ⱱ 
ⱱ 
collect 
log 
page
Adverse Event 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
If 
needed 
Patient Overall 
Evaluation 
 
 
 
 
 
ⱱ*****
 
 
ⱱ 
Physician Global 
Assessment 
 
 
 
 
 
ⱱ 
 
 
ⱱ 
Patient 
Completion 
 
 
 
 
 
 
 
 
ⱱ 
 
Photographs of patient’s breasts prior to radiation therapy: The baseline photo should be a 
close-up encompassing only the breast to be treated at a 45 degree oblique angle with arms 


23 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
elevated over the patient’s head. Other photos should be a straight frontal view of both breasts 
taken in either a standing or seated position with the patient’s hands on her hips, excluding her 
face. Boost area will be labeled prior to week 5 photo and a photo will be taken showing the 
boost area.  
Label each slide or photograph with the date and the patient case number. The 
labeled photographs will be stored electronically under study specific patient folders. 
 
** Separate photo with boost drawn on skin. 
 
*** If Patient is of child-bear
ing age and sexually active 
 
 
**** Prior to first Radiation Therapy 
 
***** Evaluation should be completed prior to boo
st, but Patient will not be removed from the 
study is this is completed after the boost. 
 
Final Visit  
This will occur at 2 weeks after the completion of radiotherapy. These forms and actions will be 
completed: 
 
Physician Fo llow-Up Assessment Form 3 
Describes the radiotherapy treatment and provides a time line to compare 
irradiated and non-irradiated breast indications 
 
Physician's Global Assessment Form 9 
 
To be completed at Week 5 prior to boost and also 2 weeks post radiation 
 Patient Overall Evaluation Form 10 
 
Used to elicit patient evaluation of prophylaxis 
 
Patient Completion Form 11 
 
Final compilation of patient data upon study completion or discontinuation 


24 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
 
APPENDIX B 
 
FORMS 


25 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
FORM 1 
 
CONSENT TO PARTICIPATE IN RESEARCH  TEMPLATE 
Instructions 
Please read this consent form carefully and take your time making a decision about whether to 
participate.  As the researchers discuss this consent form with you, please ask him/her to explain 
any words or information that you do not clearly understand.  The purpose of the study, risks, 
inconveniences, discomforts, and other important information about the study are listed below.  
If you decide to participate, you will be given a copy of this form to keep. 
 
Why is this study being done? 
The study is being done to provide information about the effectiveness and safety of a product 
containing the patented HylaSponge®System and whether the use of this product reduces the 
tissue damage that results from radiotherapy treatment.   
 
Why is this considered research?  
This is a research study because the HylaSponge®System is being compared to placebo when 
applied to the breast which is undergoing radiotherapy as part of treatment for cancer.   
 
The following definitions may help you understand this study:  
 
Double-blind means neither you nor the researchers will know which product you are 
receiving.  
 
Randomization means the products will be assigned by chance for application to either 
side of your breast.   
 
Standard medical care means the regular care you would receive from your personal 
doctor if you choose not to participate in this research. 
 
Researchers means the study doctor and research personnel at the University of Texas 
Southwestern Medical Center 
 
Why am I being asked to take part in this research study? 
You are being asked to take part in this study because you are going to be receiving radiotherapy 
as part of your treatment for breast cancer. 
 
Do I have to take part in this research study?” 
No.  You have the right to choose whether you want to take part in this research study.  If you 
decide to participate and later change your mind, you are free to stop participation at any time. 
 
If you decide not to take part in this research study it will not change your legal rights or the 
quality of health care that you receive at this center. 
 
How many people will take part in this study? 
We plan to have approximately 30 people participate in this study here at UT Southwestern.  


26 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
What is involved in the study? 
If you volunteer to take part in this research study, you will be asked to sign this consent form 
and will have the following tests and procedures.  Some of the procedures may be part of your 
standard medical care, but others are being done solely for the purpose of this study. 
 
Screening Procedures 
To help decide if you qualify to be in this study, the researchers may ask you questions about 
your health, including medications you take and any surgical procedures you have had. 
 
You may also have to fill out certain forms or have the following exams, tests or procedures: 
 
Visit 1: 
 
Demographic information (age, gender, race, ethnic origin, and skin type); 
 
Eligibility assessment and an explanation of study purposes and procedures; 
 
Complete medical history including  vital signs (temperature, pulse, respirations, blood 
pressure), height, weight, physical exam,  allergies; 
 
Record current medications, vitamins, or herbs that you are taking; 
 
Photographs of breast.  At your first visit, and at Week 5, and 2 weeks post-radiation 
treatment, photographs will be taken. Photos will be taken to exclude faces or any other 
identifying marks. Photos will only be identified by a unique subject identification 
number that contains no personal identifying information.  These photographs are part of 
the research.  You will not be able to participate in the research if you do not want to 
have photographs taken.  
 
You will be randomized to receive the investigational product to be applied to either the 
medial (inside) or lateral (outside) portion of your breast, a placebo product will be used 
on the other side. 
 
You will be given a supply of the investigational product and placebo and 
instruction/demonstration for application. 
 
During participation, you will be asked to do the following:  
 
No application of any skin care product besides the study products 
 
No use of skin products that may affect the color of your skin, such as sunless tanning 
lotions; 
 
Study Medication/Intervention 
You will be provided with the study products to apply three times a day to each side as 
designated according to your random assignment. Please be sure to wash your hands 
before and between each application of product/cream.  The creams/products will be 
labeled with your Subject Number.   
Products will be supplied by the sponsor.  This part of the study will be blinded, that 
is, both products will be packaged identically by the sponsor and labeled product A 
and product B so that neither you, nor the investigator, nor the research team will be 
able to distinguish which Product is applied to areas of radiation exposure.. 


27 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
Procedures and Evaluations during the Research 
 
     Study Visits  
 
Every week during your radiation treatment you will be assessed by an Investigator.  
 
The Investigator will evaluate the status of your skin, comparing the medial (inside) 
to the lateral (outside), and determining an overall assessment of your  skin’s 
tolerance to the radiotherapy. 
 
At your first visit, and during Week 5, and 2weeks post-radiation treatment, 
photographs will be taken.  
 
On your last day of radiation, both you and your radiation oncologist will be asked to 
complete an assessment of your skin, giving you an opportunity to report how you 
felt the creams worked, and if the skin on one side of your breast fared better than the 
other side 
 
Study Visit 9: (2 weeks after last radiotherapy)  
 
 
The physician will examine your  skin 
 
Photographs of your breast 
 
You will return of any unused investigational product, as well as empty containers 
 
 
 
We will ask you about your current medications and any changes in your 
medications 
 
We will ask you about any adverse events (side effects or medical problems) that 
you are having 
 
We will ask you to complete another patient assessment, giving you another 
opportunity to report how you felt the creams worked, and if the skin on one side 
of your breast fared better than the other side. 
 
Additionally, during the entire duration of this study, we will ask you to maintain a 
log describing when you applied the products/creams. 
 
 
 


28 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
Restricted Therapies 
o 
Drugs, procedures, and/or treatments restricted during the course of this 
study  include:  
o 
Use of any skin products on the bilateral breast, unless directed by 
physician 
o 
Application of any additional skin care products besides the study products. 
Please ask your doctor if you have any questions about the medications that you are 
taking.  
The photographs, assessments, and measurements in this study are designed for research, not for 
medical purposes.  They are not useful for finding problems or diseases.  Even though the 
researchers are not looking at this information to find or treat a medical problem, you will be told 
if they notice something unusual.  You and your regular doctor can decide together whether to 
follow up with more tests or treatment.   
 
How long can I expect to be in this study? 
Your participation in this study will last about 11 weeks. 
You can choose to stop participating for any reason at any time.   
 
What are the risks of the study? 
Study Procedure/Intervention 
Because of your participation in this study, you are subject to the following risks: You should 
discuss these with the researchers and your regular health care provider.  
 
Investigational Product 
In previous use of HylaCare™, no adverse events have been identified.   
 
Psychological Stress 
Some of the questions we will ask you as part of this study may make you feel uncomfortable.  
You may refuse to answer any of the questions, take a break or stop your participation in this 
study at any time. 
 
Loss of Confidentiality 
Any time information is collected; there is a potential risk for loss of confidentiality.  Every 
effort will be made to keep your information confidential; however, this cannot be guaranteed.  


29 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
Photographs 
You could be slightly uncomfortable during the photographic sessions when asked to position 
your body to take the photograph of your breast area. You may be uncomfortable with standing 
still for an extended period of time or from turning your body in various positions. You may be 
sensitive to the bright and repeating flashes from the camera, which can sometimes cause 
headaches, irritation of the eyes, discomfort, after effects such as seeing spots, and in rare cases, 
could stimulate a migraine headache or epileptic seizure. 
 
Photographs include a risk of identification.  Your privacy will be protected to the greatest extent 
possible.  Photos will be taken to exclude faces or any other identifying marks. Photos will only 
be identified by a unique subject identification number that contains no personal identifying 
information. For research purposes your photos may be used in scientific publications. 
 
Other Risks 
There may possibly be other side effects that are unknown at this time. If you are concerned 
about other, unknown side effects, please discuss this with the researchers. 
 
How will risks be minimized or prevented?   
You will be carefully screened prior to participation in this study to be sure that you do not have 
any conditions that would make it unsafe for you.  You will be closely monitored during the 
study.  You will be asked, at each visit, about how you are feeling and about any problems or 
changes in your health that you are having.  If you have any adverse events (side effects) from 
the study products, your surgeon will discuss appropriate treatment with you. 
 
What will my responsibilities be during the study?   
While you are part of this study, the researchers will follow you closely to determine whether 
there are problems that need medical care.  It is your responsibility to do the following: 
 
Ask questions about anything you do not understand. 
 
Keep your appointments. 
 
Follow the researchers’ instructions. 
 
Let the researchers know if your telephone number or address changes. 
 
Store study materials (containers of product) in a secure place at home away from 
anyone who is unable to read and understand labels, especially children. 
 
Tell the researchers before you take any new medication, even if it is prescribed by 
another doctor for a different medical problem or something purchased over the counter. 
 
Tell your regular doctor about your participation in this study. 
 
Report to the researchers any injury or illnesses while you are on study even if you do 
not think it is related.  
 
If I agree to take part in this research study, will I be told of any new risks that may be 
found during the course of the study? 
Yes.  You will be told if any new information becomes available during the study that could 
cause you to change your mind about continuing to participate or that is important to your health 
or safety. 


30 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
What should I do if I think I am having problems? 
If you have unusual symptoms, pain, or any other problems while you are in the study, you 
should report them to the researchers right away.  Telephone numbers where they can be reached 
are listed on the first page of this consent form. 
 
If you have a sudden, serious problem, like difficulty breathing or severe pain, go to the nearest 
hospital emergency room, or call 911 (or the correct emergency telephone number in your area).  
Tell emergency personnel about any medications you are taking. 
 
What are the possible benefits of this study? 
If you agree to take part in this study, there may or may not be direct benefits to you.  The 
researchers cannot guarantee that you will benefit from participation in this research.   You may 
benefit from a reduction in skin irritation, decreased inflammation, and improved healing, but 
this cannot be guaranteed.   
 
We hope the information learned from this study will may provide a better understanding of the 
effects of HylaCare™ on irradiated skin.   
 
What options are available if I decide not to take part in this research study? 
This is not a treatment study.  You do not have to be part of it to get treatment for your elective 
procedure. 
 
Will my insurance provider or I be charged for the costs of any part of this research study? 
No. Neither you, nor your insurance provider, will be charged for anything done only for this 
research study (i.e., the Screening Procedures, Experimental Procedures, or Monitoring/Follow-
up Procedures described above).   
 
However, the standard medical care for your condition (care you would have received whether or 
not you were in this study) is your responsibility (or the responsibility of your insurance provider 
or governmental program).  You will be charged, in the standard manner, for any procedures 
performed for your standard medical care. 
 
What will happen if I am harmed as a result of taking part in this study? 
It is important that you report any illness or injury to the research team listed at the top of this 
form immediately. 
 
Compensation for an injury resulting from your participation in this research is not available 
from the University of Texas Southwestern Medical Center at Dallas.    
 
You retain your legal rights during your participation in this research 
 
Can I stop taking part in this research study? 
Yes.  If you decide to participate and later change your mind, you are free to stop taking part in 
the research study at any time. 
 


31 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
If you decide to stop taking part in this research study, it will not affect your relationship with the 
UT Southwestern staff or doctors.  Whether you participate or not will have no effect on your 
legal rights or the quality of your health care. 
 
If you are a medical student, fellow, faculty, or staff at the Medical Center, your status will not 
be affected in any way. 
 
Your doctor may be a research investigator in this study.  S/he is interested in both your medical 
care and the conduct of this research study.  At any time, you may discuss your care with another 
doctor who is not part of this research study.  You do not have to take part in any research study 
offered by your doctor. 
 
If I agree to take part in this research study, can I be removed from the study without my 
consent? 
Yes.  The researchers may decide to take you off this study if: 
 
Your medical problem becomes worse. 
 
The researchers believe that participation in the research is no longer safe for you. 
 
The researchers believe that other treatment may be more helpful. 
 
The sponsor stops the research for the safety of the participants. 
 
The sponsor cancels the research. 
 
You are unable to keep appointments or to follow the researchers’ instructions. 
 
Will my information be kept confidential? 
Information about you that is collected for this research study will remain confidential unless you 
give your permission to share it with others, or if we are required by law to release it.  You 
should know that certain organizations that may look at and/or copy your medical records for 
research, quality assurance, and data analysis include: 
 
• 
Hylaco, LLC; 
Disease Oriented Breast Team- Surgical Oncologist, Medical Oncologist, Plastic 
surgeons  
• 
Representatives of government agencies involved in keeping research safe for people; 
and 
• 
The UT Southwestern Institutional Review Board.  
 
Medical information collected during this study and the results of any test or procedure done 
may be included in your medical record and this information may be available to health care 
providers and authorized persons including your insurance company. 
 
In addition to this consent form, you will be asked to sign an "Authorization for Use and 
Disclosure of Protected Health Information."  This authorization will give more details about 
how your information will be used for this research study, and who may see and/or get copies of 
your information. 


32 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
Are there procedures I should follow after stopping participation in this research? 
If you, the researchers, or the sponsor stops your participation in the research, you may be asked 
to do the following: 
 
 
Let the researchers know immediately that you wish to withdraw from the research. 
 
Return to the research center for tests that may be needed for your safety. 
 
Return any unused study materials, including empty containers. 
 
Discuss your future medical care, if any, with the researchers and/or your personal 
doctor. 
 
Whom do I call if I have questions or problems? 
For questions about the study, Asal Rahimi MD 214 645-8525 
For questions about your rights as a research participant, contact the UT Southwestern 
Institutional Review Board (IRB) Office at 214-648-3060. 
 
SIGNATURES: 
 
YOU WILL BE GIVEN A COPY OF THIS CONSENT FORM TO KEEP. 
 
Your signature below certifies the following: 
 
•  You have read (or been read) the information provided above. 
•  You have received answers to all of your questions and have been told whom to call if you 
have any more questions. 
•  You have freely decided to participate in this research. 
•  You understand that you are not giving up any of your legal rights. 
You understand that a copy of this signed consent document, information about this study 
d the results of any test or procedure done may be included in your medical record and this 
ormation may be available to health care providers and authorized persons including your 
urance company. 
   
 
__________________________________________________ 
Participant’s Name (printed) 
 
 
__________________________________________________ 
Participant’s Signature 
 
_______________ 
Date 
__________________________________________________ 
Name of person obtaining consent (printed) 
 
 
__________________________________________________ 
Signature of person obtaining consent 
 
________________ 
Date 


3 3 
1 4 0 5 0 7 H yla Care 
R a n d o miz e d, D o u bl e- Bli n d, V e hi cl e C o ntr oll e d Pil ot St u d y of t h e Effi c a c y a n d S af et y of H yl a C ar e T M    i n t h e Pr o p h yl a xi s of A c ut e S ki n 
C h a n g e s i n P ati e nt s U n d er g oi n g E xt er n al B e a m R a di ot h er a p y f or  T u m or s of t h e Br e a st  
 
F O R M 2 A 
T est Articl e: Hyl a C ar e T M   
 
P ati e nt N o.: 
St u dy N o.:  
I N C L U SI O N C RI T E RI A 
I nv esti g at or’s N a m e: 
 
T o d ay’s D at e: 
 
 
 
 
F or t h e p ati e nt t o b e i n cl u d e d i n t h e st u d y, all a n s w er s t o t h e f oll o wi n g q u e sti o n s 1- 6 m u st b e c h e c k e d Y E S, 
A N D at l e a st t h e a n s w er t o o n e p art of q u e sti o n 7 m u st b e c h e c k e d Y E S 
 
 
Y E S  
N O 
1. Is t h e p ati e nt 1 8 y e ars or ol d er ? 
 
 
2. Is t h er e a di a g n osis of c a nc er of t h e br e ast ? 
 
 
4. Will t h e pl a n n e d r a di ot h er a py b e a d mi nist er e d vi a t a n g e nti al p orts ? 
 
 
5. H as t h e p ati e nt pr ovi d e d a pri or writt e n I nf or m e d C o ns e nt f or m t ? 
 
 
6. D o es t h e p ati e nt h av e t h e a bility t o u n d erst a n d a d c o m ply wit h t h e r e q uir e m e nts of t his st u dy ? 
 
 
7. F or s ex u ally activ e f e m al es, o n e of t h e a ns w ers pr ovi d e d b el o w m ust b e “ Y E S” 
 
 
  
a. H as t h e p ati e nt a gr e e d t o us e a n acc e pta bl e m et h o d of birt h c o ntr ol; or t ak e or al 
  
c o ntr ac e ptiv es f or at l e ast o n e m o nt h pri or t o st u dy a n d f or t h e d ur ati o n of t h e st u dy ? 
 
 
  
b. B e e n st eril e, i nf ertil e or ot h er wis e i nc a p a bl e of b ec o mi n g pr e g n a nt, or 
 
 
  
c. b e e n p ost- m e n o p a us al f or at l e ast o n e y e ar ? 
 
 
 
 
 
 
I nv esti g at or’s Si g n at ur e:   
  
  
  
  
  
D at e:    
  
 


3 4 
1 4 0 5 0 7 H yla Care 
R a n d o miz e d, D o u bl e- Bli n d, V e hi cl e C o ntr oll e d Pil ot St u d y of t h e Effi c a c y a n d S af et y of H yl a C ar e T M    i n t h e Pr o p h yl a xi s of A c ut e S ki n 
C h a n g e s i n P ati e nt s U n d er g oi n g E xt er n al B e a m R a di ot h er a p y f or  T u m or s of t h e Br e a st  
 
 
 
 
F O R M 2 B 
T est Articl e: Hyl a C ar e T M   
 
P ati e nt N o.: 
St u dy N o.:  
E X C L U SI O N C RI T E RI A  
I nv esti g at or’s N a m e: 
 
T o d ay’s D at e: 
 
 
 
F or t h e p ati e nt t o b e i n cl u d e d i n t h e st u d y, all a n s w er s t o t h e f oll o wi n g q u e sti o n s m u st b e c h e c k e d N O 
 
 
Y E S  
N O 
1. Is t h e p ati e nt eit h er pr e g n a nt or  l act ati n g ? 
 
 
2. Is t h e p ati e nt usi n g a ny m e dic ati o n t h at mi g ht i nt erf er e wi t h t h e i nt er pr et ati o n of                   
t h e t est articl e’s eff ectiv e n ess or s af ety ? 
 
 
3. Will t h e p ati e nt b e usi n g a ny c o nc o mit a nt ski n c ar e pr e p ar ati o ns o n a ny of t h e irr a di at e d 
ar e as ? 
 
 
4. D o es t h e p ati e nt h av e a ny i nf ecti o n or u n h e al e d w o u n d i n t h e i nt e n d e d r a di ot h er a py ski n p ort 
ar e as ? 
 
 
5. D o es t h e p ati e nt h av e a ny f or m of g e n er aliz e d d er m at osis ? 
 
 
6. D o es t h e p ati e nt h av e a ny k n o w n dis e as e  t o aff ect t h e ski n h e ali n g pr oc ess ?                             
( e. g. s ev er e r e n al f ail ur e, etc.) ? 
 
 
7.  D o es t h e p ati e nt h av e a hist ory of a n a p hyl axis or m ulti pl e s ev er e all er gi es ? 
 
 
8. D o es t h e p ati e nt h av e a hist ory of all er gy t o avi a n-s o urc e d pr ot ei n pr o d ucts ?                              
( e. g., c hick e n, e g gs) ? 
 
 
9. D o es t h e p ati e nt pl a n t o r el oc at e d uri n g t h e c o urs e of t h e st u dy,  m aki n g sc h e d ul e d visits 
i m p ossi bl e ? 
1 0.  D o es t h e p ati e nt  h av e c oll a g e n v asc ul ar dis e as e ( L u p us, scl er o d er m a) ? 
 
 
 
 
 
 
 
 
 
 
 
 
 
I nv esti g at or’s Si g n at ur e:   
  
  
  
  
D at e:    
  
 
 


35 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
Test Article: HylaCareTM   
 
 
FORM 3 
 
Patient No.: 
Study No.:  
Physician’s Follow-Up 
Assessment Form 
Investigator’s Name: 
 
Today’s Date: 
 
 
Date Radiotherapy Initiated (mm/dd/yy): _____/_____/_____ 
 
Number of weeks of RT completed: 5___ 
2 weeks post-treatment___ 
Check (X) signs or symptoms reported by the patient at the irradiated skin areas: 
 
Indication 
Right breast 
Left Breast
Which side of 
IRRADIATED BREAST 
ONLY is worse? 
(M/L/ equal) 
 
Medi
al 
Lateral 
 
Medial 
Lateral 
Redness 
 
 
 
 
 
 
 
 
Pain 
 
 
 
 
 
 
 
 
Tenderness 
 
 
 
 
 
 
 
 
Easily Irritated 
 
 
 
 
 
 
 
 
Burning 
 
 
 
 
 
 
 
 
Dryness 
 
 
 
 
 
 
 
 
Hypersensitive 
 
 
 
 
 
 
 
 
Hair Loss 
 
 
 
 
 
 
 
 
Other 
(describe) 
 
 
 
 
 
 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
[Form 3, continued] 
 


36 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
I.  Grading NCIC-CTC 
Adverse Event 
1 
2 
3
4
5 
Dermatitis 
radiation 
Faint erythema or 
dry desquamation 
Moderate to brisk 
erythema; 
desquamation 
patchy moist 
desquamation, 
mostly confined to 
skin folds and 
creases moderate 
edema 
 
Moist 
desquamation in 
areas other than 
skin folds and 
creases  
bleeding induced 
by minor trauma or 
abrasion 
Life-threatening 
consequences; 
skin necrosis or 
ulceration of full 
thickness dermis; 
spontaneous 
bleeding from 
involved site; skin 
graft indicated 
Death
Definition: A finding of cutaneous inflammatory reaction occurring as a result of exposure to biologically effective levels of ionizing
radiation 
 
 
Please use NCIC-CTC grading and diagram below: 
 
 
 
 
 
 
 
 
 
 
 
II. In addition, using the Investigator Grading Scal
e, grade the status of the medial and lateral 
sides of the irradiated skin as: 
 
0 = normal skin 
1 = light epidermal irritation, consisting of the onset of erythema, possibly associated 
with slight edema 
2 = erythema with dry desquamation 
3 = wet desquamation </= 2 cm 
 
4 = wet desquamation from 2.1 – 5 cm
  
5 = wet desquamation from 5.1 - 9 cm 
 
6 =  wet desquamation > 9.1 cm
 
 
 
 
 
 
 
 
 
 
Investigator’s Signature: 
 
 
 
 
_______Date:  
 
 
 
 
[Form 3, continued] 
 


37 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
 
 
If there is any skin desquamation, note minimal and maximal desquamation size: 
Medial:  __________  mm minimal x __________ mm maximal 
Lateral: __________  mm minimal x __________ mm maximal 
 
Most severe desquamation is dry___ or wet_____? 
 
At  2-week Post-Radiation visit: Describe any treatment performed: 
Skin cleansing:__________________________________________________________________ 
Other (describe):_________________________________________________________________ 
 
Please grade the current status of desquamation healing at 2-week Post-Radiation visit:   
Right Breast 
Medial:  __________ 
 
1 = no evidence of healing (or worsening) 
 
 
 
 
2 = Beginning of proliferation 
 
 
 
 
3 = Tissue granulation 
Lateral:  __________  
4 = Re-epithelialization 
 
Left Breast 
Medial:  __________ 
 
1 = no evidence of healing (or worsening) 
 
 
 
 
2 = Beginning of proliferation 
 
 
 
 
3 = Tissue granulation 
Lateral:  __________  
4 = Re-epithelialization 
 
Has the patient started any concomitant medication(s) since the last visit, or has the medication 
dosage changed?  If yes, please list below. 
Medication 
Dose 
indication 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Has the patient reported any adverse events since the last visit?     Yes: _____     No: _____ 
If Yes, please list below and complete Adverse Event Form. 
I 
 
Investigator’s Signature: 
 
 
 
 
 
________Date:  
 
 
 
 
 


38 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
Test Article: HylaCareTM   
FORM 4 
Patient No.: 
Study No.:  
DEMOGRAPHICS  
Investigator’s Name: 
AND MEDICAL HISTORY 
Today’s Date: 
 
PATIENT DEMOGRAPHICS 
 
 
Date of Birth (mm/dd/yy):   
 
 
SEX:   
Female  
Height (inches):   
 
 
 
Weight (pounds):  
 
 
 
Race:   
 
 
 
 
                        
1=White;  
2=Black;  
3=Hispanic;  
4=Asian;  
5=Other, specify 
 
BMI: _________                           Breast Cup Size:  __________ 
 
 
MEDICAL HISTORY 
(Check appropriate boxes) 
System 
Normal 
Abnormal 
If Abnormal, specify: 
Allergies 
 
 
 
Drug Sensitivities 
 
 
 
Dermatologic 
 
 
 
HEENT 
 
 
 
Cardiovascular 
 
 
 
Pulmonary 
 
 
 
Gastrointestinal 
 
 
 
Renal 
 
 
 
Endocrine-metabolic 
 
 
 
GU Systems 
 
 
 
Musculoskeletal 
 
 
 
Peripheral Vascular 
 
 
 
Neurological 
 
 
 
Psychiatric 
 
 
 
Other 
 
 
 
 
Additional comments on Medical History findings (if any):  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
Investigator’s Signature:  
 
 
 
 
 
Date: 
 
 
 


39 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
 
 
 
Test Article:  HylaCareTM   
 
Patient No.: 
Study No.:  
FORM 5 
GENERAL PHYSICAL  
Investigator’s Name: 
EXAMINATION 
Today’s Date: 
 
 
PHYSICAL EXAMINATION 
Normal 
Abnormal 
If Abnormal, specify: 
Head and Neck  
 
 
 
Skin and Mucosa 
 
 
 
Eyes 
 
 
 
Lymph Nodes 
 
 
 
Cardiovascular 
 
 
 
Chest and Lungs 
 
 
 
Abdomen 
 
 
 
Musculoskeletal 
 
 
 
Other 
 
 
 
 
 
 
 
 
Additional Comments (if any): 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator’s Signature:  
 
 
 
 
 
Date: 
 
 
 


40 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
 
 
 
Test Article: HylaCareTM   
 
Patient No.: 
Study No.:  
FORM 6 
RADIOTHERAPY  
Investigator’s Name: 
TREATMENT FORM 
Today’s Date: 
 
Date of first radiotherapy session (mm/dd/yy): _____/_____/_____ 
 
Maximum Hot spot: 
 
Circle whether 6MV 15MV 18 MV or MIXED PHOTONS are used. 
 
If mixed photons are used, please note weighting of each photon energy. 
 
#cc’s receiving greater than 107% prescription dose: ____________ 
 
#cc’s receiving greater than 110% prescription dose:_____________ 
 
# of cc’s of breast tissue in the tangential field (breast tangents including chest wall and ribs) 
 
Whole breast radiation prescription dose: ____________ Maximum dose: ______________ 
 
Which breast is being irradiated? Right ____ Left_______ 
 
 
 
 
 
 
 
 
Investigator’s Signature: 
 
 
 
 
 
Date:  
 
 


41 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
 
Test Article: HylaCareTM   
FORM 7 
PATIENT DAILY LOG 
Patient No.: 
Study No.:  
 
Investigator’s Name: 
 
 
Today’s Date: 
 
 
Day (Date) 
Morning 
(time of application) 
Afternoon 
(time of application) 
Evening 
(time of application) 
Monday 
 
 
 
 
Tuesday 
 
 
 
 
Wednesday 
 
 
 
 
Thursday 
 
 
 
 
Friday 
 
 
 
 
Saturday 
 
 
 
 
Sunday 
 
 
 
 
Day (Date) 
Morning 
(time of application) 
Afternoon 
(time of application) 
Evening 
(time of application) 
Monday 
 
 
 
 
Tuesday 
 
 
 
 
Wednesday 
 
 
 
 
Thursday 
 
 
 
 
Friday 
 
 
 
 
Saturday 
 
 
 
 
Sunday 
 
 
 
 
Day (Date) 
Morning 
(time of application) 
Afternoon 
(time of application) 
Evening 
(time of application) 
Monday 
 
 
 
 
Tuesday 
 
 
 
 
Wednesday 
 
 
 
 
Thursday 
 
 
 
 
Friday 
 
 
 
 
Saturday 
 
 
 
 
Sunday 
 
 
 
 


42 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
Test Article: HylaCareTM   
FORM 8 
PATIENT INSTRUCTIONS FORM  
Patient No.: 
Study No.:  
(to be given to the patient!) 
Investigator’s Name: 
 
Today’s Date: 
 
You have been given two nearly identical pump containers of serum to be applied to your irradiated 
skin three times a day.  The label on each container will tell you on which side to apply the serum, 
either medial (inside) or lateral (outside).  The picture below shows you which container should be 
used on which location.   
 
At Baseline visit or first week of treatment, at Week 3, Week 5 and 2 weeks post‐treatment you will 
be given sufficient Set Bags as needed to complete the study. 
 
 
 
Please outline the areas of skin that will be subject to irradiation.  Note areas to be 
included in study with a CIRCLE, and note areas outside study area with an X. 
 
 
 
 
 
 
 
 
 
Use diagram to indicate which jar to use on which portion of breast. 
Note: 
(1) The above-outlined areas, within the circles to indicate inclusion in the study, are the 
ones to which the test article products are be applied. 
(2) The patient will be instructed how, where, and how much product to apply to each 
irradiated skin area. 
(3) The patient will also be instructed to apply these products only to the encircled areas, 
and not to apply any other skin care products to these sites. 
 
 
 
 
 
 
 
 
 
 
 
 
 


43 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
Application Methods 
Ensure that your hands are clean, then use the pump to dispense an adequate amount of serum.    
Apply enough serum to cover the entire area noted in the diagram.  Wash your hands again, before 
switching to the other serum and applying to the other side.  Do not use any other products on the 
treatment areas. 
 
 
 
 
 
 
 
 
 
Additional Information 
Apply serums three times a day, every day, but ensure that you don’t apply anything to your 
skin within 4 hours before your radiotherapy appointment. 
Ensure that you apply the serums IMMEDIATELY AFTER  radiotherapy treatment. 
Apply only to the area identified for prophylaxis. 
 
Report any reactions (general or localized) to the investigator at the next daily session, or more 
severe reactions by telephone. 
Suggestions for personal care of the irradiated skin 
1. 
 Avoid irritating the skin 
2. 
When washing, use only lukewarm water and mild soap, patting the surface dry 
3. 
Avoid the use of tight clothing 
4. 
Do not rub, scrub or scratch the skin 
5. 
Avoid the use of heating pads or ice packs 
6. 
Do not use powders, creams , perfumes, deodorants, body oils, ointments or lotions on the 
irradiated surfaces 
7. 
Avoid direct sun exposure, if necessary, wear protective clothing


44 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
Study No.:  
Form 9 
 PHYSICIAN’S GLOBAL 
Patient No.: 
Investigator’s Name: 
ASSESSMENT FORM 
Today’s Date: 
 
Note: This form should be completed at Week 5 
prior to boost and at the end of study 
(2 weeks after completion of RT). 
Please make an overall global
 assessment of the effect
iveness of radiation skin 
tolerance of both sides of 
the irradiated breast tissue. Based on your judgment and 
past experience, compare the skin appearance and patient’s reported symptomatology 
for each side of the breast, and for each breas
t (test substance-treated and vehicle 
control-treated) with the normally expected 
degree of radiation damage for similar body 
sites. Grade your overall impression as: 
 
 
0 = poor (worse than typical expectations) 
 
1 = fair (equal to, or slightly
 better than typical expectations) 
 
2 = good (moderately better than typical expectations) 
 
3 = excellent (markedly bette
r than typical expectations) 
 
Please compare the two irradiat
ed sites. In your opinion, 
which skin site fared better, 
based on symptoms experienc
e by the patient and overall skin appearance? 
 
Right Breast: 
Medial: __________ Lat
eral: __________ Equal Tolerance: __________ 
Left Breast 
Medial: __________ Later
al: __________ Equal
 Tolerance: __________ 
 
Comments: 
 
 
 
______________________________________________________________________
______________________________________________________________________
______________________________________________________________________
__________________________________________________________ 
 
 
Investigator’s Signature:  
 
 
 
 
 
Date: 
 
 
 


45 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
 
Test Article: HylaCareTM   
FORM 10 
PATIENT’S OVERALL 
Patient No.: 
Study No.:  
EVALUATION FORM 
Investigator’s Name: 
 
Today’s Date: 
 
Note: The patient should complete this questionna
ire at Week 5 prior to boost and at 
the final visit (2 weeks a
fter the completion of RT). 
 
Instructions to the Patient 
 
You have now completed your 
prescribed course of radiot
herapy administrated to your 
breast. 
Please compare the two sides 
(medial [inner] and lateral [out
er]) of your irradiated 
breast which were exposed to radiation. 
 
In terms of any localized skin reactions you have experiences throughout your 
radiotherapy (such as redness, so
reness, itching, or others), which side of the irradiated 
breast do you believe fared better. 
__________Medial better than late
ral (inner better than outer) 
__________Lateral better than medial (outer better than inner) 
__________No difference between medial (inner) and lateral (outer) 
 
Which side of the irradiated breast has main
tained an overall appearance closest to its 
appearance before ra diotherapy began? 
__________Medial (inner) 
__________Lateral (outer) 
__________No difference between medial (inner) and lateral (outer) 
 
Do you have any preferences between 
the serums applied to your skin ? 
__________Prefer the product applie
d to medial side (inner) 
__________Prefer the product applie
d to lateral side (outer) 
__________No preference bet ween the two products 
 
 
 
 
 
 
If you did prefer one product over 
the other, please explain why: 
______________________________________________________________________
______________________________________________________________________ 
 
Investigator’s Signature:  
 
 
 
 
 
Date: 
 
 
 


46 
140507 HylaCare 
Randomized, Double-Blind, Vehicle Controlled Pilot Study of the Efficacy and Safety of HylaCareTM    in the Prophylaxis of Acute Skin 
Changes in Patients Undergoing External Beam Radiotherapy for  Tumors of the Breast 
 
Test Article: HylaCareTM   
FORM 11 
PATIENT  
Patient No.: 
Study No.:  
COMPLETION FORM 
Investigator’s Name: 
 
Today’s Date: 
 
Note:  To be completed at the final visit, or upon discontinuation from the study. 
 
1.Subject Overview 
Did the patient experience any side effects from the study agent?      
Yes: _____  No: _____ 
 
If yes, complete Adverse Event Form 
 
2.Study Completion 
Did the patient complete the entire study? 
 
 
 
Yes: _____  No: _____ 
 
If no, complete information below. 
 
3.Discontinuation from Study 
Date of withdrawal (mm/dd/yy):   _____/_____/_____ 
 
Reason for withdrawal (check and explain) 
_____Adverse Event:____________________________________________________________________ 
_____Did not meet protocol criteria:_________________________________________________________ 
_____Unreliable:_______________________________________________________________________ 
_____Lost to follow-up/moved:_____________________________________________________________ 
_____Subject requested discontinuation:_____________________________________________________ 
_____Other:___________________________________________________________________________ 
 
Explain (in detail, as needed)  
_____________________________________________________________________________________
_____________________________________________________________________________________
__________________________________________________________________________________ 
 
 
I have reviewed and evaluated the information provided in these case report forms and believe it accurate 
represents the patient’s clinical progress in the study. 
 
 
Investigator’s Signature:  
 
 
 
 
 
Date: