A Randomized Phase II Double-Blinded Study of The Efficacy of Oleogel-S10 (AP101) Gel for the Treatment of Grade 2/3 Radiation Dermatitis in Breast Cancer Patients
Phase: PHASE2
Conditions: Breast Cancer, Breast Cancer Stage, Breast Cancer Stage I, Breast Cancer Stage II, Breast Cancer Stage III, Breast Cancer Stage IV
Sponsor: Memorial Sloan Kettering Cancer Center

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
 
MSK PROTOCOL COVER SHEET 
A Randomized Phase II Double-Blinded Study of the Efficacy of Oleogel-S10 (AP101) 
Gel for the Treatment of Grade 2/3 Radiation Dermatitis in Breast Cancer Patients 
 
Principal Investigator/Department: Alina Markova, MD/Medicine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 1 of 37 

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
Memorial Sloan Kettering Cancer Center 
1275 York Avenue 
New York, New York 10065 
Page 2 of 37 
 
 
Table of Contents 
1.0 
PROTOCOL SUMMARY AND/OR SCHEMA ......................................................................... 4 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS .................................................................................. 4 
3.0 
BACKGROUND AND RATIONALE ........................................................................................ 5 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION................................................................. 7 
4.1 
Design ................................................................................................................................. 7 
4.2 
Intervention .......................................................................................................................... 8 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS .............. 8 
6.0 
CRITERIA FOR PARTICIPANT ELIGIBILITY ....................................................................... 14 
6.1 
Participant Inclusion Criteria .............................................................................................. 14 
6.2 
Participant Exclusion Criteria ............................................................................................. 15 
7.0 
RECRUITMENT PLAN ......................................................................................................... 15 
7.1 
Research Participant Registration ...................................................................................... 16 
7.2 
Randomization................................................................................................................... 17 
7.3 
Blinding ............................................................................................................................. 17 
7.4 
Unblinding ......................................................................................................................... 17 
8.0 
INFORMED CONSENT PROCEDURES ................................................................................ 17 
9.0 
PRE-TREATMENT/INTERVENTION ..................................................................................... 18 
10.0 TREATMENT/INTERVENTION PLAN .................................................................................. 19 
11.0 EVALUATION DURING TREATMENT/INTERVENTION ...................................................... 21 
12.0 CRITERIA FOR REMOVAL FROM STUDY .......................................................................... 22 
13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY .................. 22 
14.0 BIOSTATISTICS ................................................................................................................... 25 
15.0 TOXICITIES/RISKS/SIDE EFFECTS .................................................................................... 28 
15.1 Serious Adverse Event (SAE) Reporting ............................................................................ 32 
15.2 
External SAE Reporting ..................................................................................................... 33 
15.3 
Reporting to Amryt Pharma ............................................................................................... 33 
16.0 PROTECTION OF HUMAN PARTICIPANTS ........................................................................ 34 
16.1 Privacy .............................................................................................................................. 35 
  16.2  Data Management ............................................................................................................. 35 
16.3 Quality Assurance ............................................................................................................. 36 
16.4 Data and Safety Monitoring ............................................................................................... 36 

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IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
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New York, New York 10065 
Page 3 of 37 
 
 
17.0 
REFERENCES ..................................................................................................................... 37 
18.0 
APPENDICES ...................................................................................................................... 37 

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IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
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1.0 
PROTOCOL SUMMARY AND/OR SCHEMA 
Title: A Randomized Phase II Double-Blinded Study of the Efficacy of Oleogel-S10 (AP101) Gel for 
the Treatment of Grade 2/3 Radiation Dermatitis in Breast Cancer Patients. 
Funding: Amryt Research 
Total Study Follow-up per Patient: 27 weeks 
Schema: 
 
 
 
Onset of grade 2-3 
radiation dermatitis 
after Fraction Day 20 (of 
25 total fractions) or after 
Fraction Day 25 (of 30 
total fractions) of 
Radiation Therapy (RT) 
 
Patients with breast 
cancer developing 
grade 2/3 radiation 
dermatitis 
N = 50 
 
 
Randomization into 
Oleogel-S10 + 
triamcinolone 0.1% 
cream vs triamcinolone 
0.1% cream 
Study Day 0 to Day 21 
triamcinolone 0.1% 
cream QAM + 
Oleogel-S10 QHS 
N = 25 
 
triamcinolone 0.1% 
cream QAM + 
vehicle gel QHS 
N = 25 
 
 
 
 
2.0 
OBJECTIVES AND SCIENTIFIC AIMS 
Primary Objective: 
• 
To assess the efficacy of topical Oleogel-S10 gel vs placebo (vehicle gel) when 
added to standard of care (triamcinolone 0.1% cream) in reducing radiation wound 
body surface area, when applied for 14 days to the radiated area of skin in patients 
with breast cancers and grade 2/3 dermatitis. 
Secondary Objectives: 
• 
To assess the efficacy of topical Oleogel-S10 gel vs placebo (vehicle gel) when 
added to standard of care (triamcinolone 0.1% cream) in reducing radiation wound 
Study Completion 
Week 27 Follow-Up Visit 
N=50 

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IRB Number: 21-091 A(10) 
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Page 5 of 37 
 
 
body surface area, when applied for 21 days to the radiated area of skin in patients 
with breast cancers and grade 2/3 dermatitis. 
• 
To determine the effect of topical Oleogel-S10 gel vs placebo (vehicle gel) 
when added to standard of care (triamcinolone 0.1% cream) on the time to 
resolution of grade 2/3 radiation dermatitis via standardized photography. 
• 
To evaluate adverse events (AEs) as determined by CTCAE v5.0 grading 
• 
To assess health-related quality of life (HRQoL), as assessed by PRO- 
CTCAE (Appendix III) and the Radiation-Induced Skin Reaction Assessment 
Scale (RISRAS) (Appendix IIB). 
 
Exploratory Objectives: 
• 
To characterize time to resolution of ARD in intertriginous vs non- 
intertriginous skin and with respect to radiation dose. 
• 
To characterize late effects of radiation, such as fibrosis, telangiectasias, 
hyperpigmentation, and dermatitis. 
• 
To characterize the typical timeline of AE occurance. 
• 
To assess patient compliance with the application of topical Oleogel-S10 gel 
or placebo 
 
3.0 
BACKGROUND AND RATIONALE 
Radiation therapy (RT) is an essential treatment for people with cancer, but is associated with 
significant toxicities. After breast-conserving surgery, radiotherapy to the conserved breast halves 
reduces the rate at which the disease recurs and the breast cancer death rate by about a sixth1. 
Memorial Sloan Kettering Cancer Center Department of Radiation Oncology annually treats 1000 
post-mastectomy patients (~400 at MSK Main; ~600 at MSK regionals) and ~1400 post-lumpectomy 
patients (~500 at MSK Main; ~900 at MSK Regionals) with breast cancer with external beam 
radiation, of whom approximately 43.8% are expected to develop grade 2-3 acute radiation 
dermatitis (ARD) with moist desquamation, providing a compelling rationale for effective prophylactic 
skin interventions and highlighting a need for therapeutic development. Standard of care guidelines 
for radiation dermatitis prevention have been developed at MSKCC for patients receiving post- 
mastectomy radiation therapy. These guidelines recommend application of topical steroids twice 
daily from day 0 of radiation through two weeks after completion of radiation. While topical steroids 
are established as an effective prophylactic therapy for acute radiation dermatitis2 in post- 
mastectomy patients by reducing the incidence of moist desquamation (g2-3 ARD) from 66.7% to 
43.8%, there is a paucity of therapies to expedite healing of acute (grade 2 to 3) radiation dermatitis 
wounds. Furthermore, MSKCC patients receiving radiation therapy without mastectomy (e.g., after 
lumpectomy) are routinely treated with topical steroids. 
Topical Oleogel-S10 would augment the wound care armamentarium to treat ARD wounds. Oleogel- 
S10 is a sterile gel consisting of 10% dry triterpene extract (TE) refined from Betulae cortex (birch 

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
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New York, New York 10065 
Page 6 of 37 
 
 
bark) of which 72% to 88% is betulin, and the remaining ingredients are primarily betulinic acid, 
lupeol, oleanolic acid, erythrodiol, and residue of the extraction solvent and 90% sunflower oil. 
Oleogel-S10 Mechanism of Action3: 
 
 
In January 2016 Oleogel-S10 received a marketing authorization in the European Economic Area 
under the tradename Episalvan® for the treatment of partial thickness wounds in adults (Episalvan 
EPAR, first published 05Feb2016) and on 9/10/2018, the US FDA granted Investigational New Drug 
(IND) clearance to Oleogel-S10. 
Pivotal clinical studies were performed in patients with split-thickness skin graft (STSG) donor sites 
wounds and in patients with Grade 2a burn wounds4. The primary efficacy end-point in the two 
pivotal studies on STSG donor sites wounds were intra-individual difference in time to wound 
closure (at least 95% epithelialization) between wound halves, either treated with Oleogel-S10 
(AP101) gel and non-adhesive wound dressing, or with non-adhesive wound dressing alone. In 

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IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
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Page 7 of 37 
 
 
both pivotal studies, Oleogel-S10 gel met the primary end-point and was significantly superior in 
both studies compared to standard dressing. In the first study, the mean time from surgery to wound 
closure was 17.1 days with standard of care treatment and 15.5 days when the wound was treated 
with Oleogel-S10 gel every 3 to 4 days or more frequently depending on dressing changes5. The 
mean intra-individual difference in time to wound closure between the wound halves was -1.4 days. 
The difference was statistically significant (p<0.0001). The results in the second study were 
consistent with the first study. The mean time from surgery to wound closure was 16.0 days with 
standard dressing and 15.1 days when the wound was treated with Oleogel-S10 gel. The mean 
intra-individual difference in time to wound closure between the wound halves was -0.8 days and 
again statistically significant (p<0.0232)4. 
In the pivotal study performed in patients with Grade 2a partial thickness burn wounds who received 
Oleogel-S10 application at least every other day with dressing changes6, the primary endpoint was 
percentage of patients showing earlier healing of the Oleogel-S10 gel treated wound half compared 
with the Octenilin® Wound Gel treated half. 85.7% of all treated patients had faster healing with 
Oleogel-S10 gel6. According to the mean expert evaluation, the mean time from the burn accident to 
wound closure was 7.6 days for Oleogel-S10 gel and 8.8 days for Octenilin® Wound Gel4. 
We hypothesize application of topical Oleogel-S10 to grade 2 – 3 acute radiation dermatitis wounds 
after radiation for breast cancer would expedite wound healing, leading to improvements in patients’ 
quality of life. 
 
 
4.0 
OVERVIEW OF STUDY DESIGN/INTERVENTION 
4.1 
Design 
Design: This is a single-center, prospective, randomized, double-blind study. 
Purpose: This study is designed to to evaluate the efficacy of topical Oleogel-S10 gel when 
used as an adjunctive treatment to topical corticosteroids (indicated for the treatment of skin 
dermatoses) for the treatment of grade 2/3 radiation dermatitis 
Patient population: Patients 18 years or older with breast cancer and radiation dermatitis 
grade 2/3. 
Duration and follow-up: A total of 50 patients with breast cancer experiencing grade 2/3 
radiodermatitis during their last 5 fractions of radiation therapy (i.e., after fraction day 20 
(when completing 25 total fractions) or after fraction day 25 (when completing 30 total 
fractions inlusive of a 5 fraction boost)) of radiation therapy will be enrolled, such that 25 
patients with breast cancer will be randomized to triamcinolone 0.1% cream once every 
morning (QAM) and vehicle gel once prior to bedtime (QHS) and 25 patients will be 
randomized to triamcinolone 0.1% cream QAM and topical Oleogel-S10 gel QHS for a 3 
week period. The primary assessment will be measured at Calendar Day 14 after start of 

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
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Page 8 of 37 
 
 
topical application of Oleogel-S10 gel or vehicle gel. Completion of the study will be followed 
by a safety visit at 7 weeks (Day 49). Each patient will be on treatment for 21 days unless 
they experience any progression of RD to grade 4+, or intolerable or serious treatment- 
related AE. At 24 weeks (Day 168) after completion of radiation the patient will return to the 
clinic to assess for effects of the investigational treatment on the late effects of radiation. 
4.2 
Intervention 
Patients who are receiving radiation therapy for breast cancer will be treated with either 
triamcinolone 0.1% cream QAM and vehicle gel QHS; or triamcinolone 0.1% cream QAM 
and topical Oleogel-S10 gel QHS for 21 days. At the time of grade 2/3 RD, patients will be 
enrolled into the study. All patients will have standard of care (SOC) triamcinolone 0.1% 
cream applied to the area of radiation QAM. Patients randomized into Oleogel-S10 will have 
Oleogel-S10 applied onto the area of radiation QHS. Those randomized to the comparator 
arm will have a vehicle/placebo gel applied to the area of radiation QHS, once a day for 21 
days. For both study arms, treatment will continue for a period of 21 days, or until 
progression of RD to grade 4+, intolerable adverse event (AE) or serious AE related to the 
investigational agent. 
Enrolled patients will be treated with our standard MSK fractionation for PMRT of 50Gy/2Gy 
per fraction or post-lumpectomy with dose and fractionation per physician discretion allowing 
both a 3D conformal and IMRT/VMAT planning technique. A chest wall boost for PMRT is 
allowed if indicated. Hypofractionation for PMRT will not be allowed. The use of bolus for our 
PMRT or post-lumpectomy patients is standardized by our MSK bolus guidelines policy. The 
thickness of bolus will be noted for each patient. 
Standardized photos, grading with CTCAE, PRO-CTCAE and Radiation-Induced Skin 
Reaction Assessment Scale (RISRAS) will be obtained every week from day 0 of trial 
through day 21; and then subsequently at the week 7 safety visit (Day 49), and 24- week 
(Day 168) long-term follow up visit. 
5.0 
THERAPEUTIC/DIAGNOSTIC AGENTS & NON-THERAPEUTIC ASSESSMENTS 
5.1 Study drug, packing, and labeling 
Oleogel-S10 
The study drug to be used in the course of this study is Oleogel-S10 which is a gel of 10% 
Triterpene Extract (Birch bark extract) and 90% sunflower gel7. 
 
The investigational product, Oleogel-S10, is a colourless to slightly yellowish, opalescent gel 
packed in white collapsible aluminium tubes containing 23.4 g gel each. Tamper-evident 
aluminium membranes close the tubes, which are fitted with white polypropylene screw caps. 
The single-use tubes are packed in cardboard boxes. The investigational product will be 
packed and labelled according to applicable regulatory requirements. 

Memorial Sloan Kettering Cancer Center 
IRB Number: 21-091 A(10) 
Approval date: 13-Feb-2024 
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Page 9 of 37 
 
 
Oleogel-S10 Structural Formula: 
 
 
Description of the Vehicle 
For clarification, please note that the term “vehicle” describes the placebo throughout this 
protocol. 
The sterile vehicle gel matches Oleogel-S10 in texture and visual appearance. 100 g of the 
vehicle gel will consist of 85 g sunflower oil, 5 g Cera flava/yellow wax, and 10 g Carnauba 
wax. 
The SoC cream used in all patients is Triamcinolone acetonide 
MF: C25H32ClFO5; IUPAC Name: [(8S,9R,10S,11S,13S,14S,16S,17R)-17-(2-chloroacetyl)-9- 
fluoro-11-hydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16- 
octahydrocyclopenta[a]phenanthren-17-yl] propanoate. 
 
Chemical Properties: 
Oleogel-S10 
Extract (as dry extract, refined) from birch bark from Betula pendula Roth, Betula pubescens 
Ehrh. as well as hybrids of both species (yield 10-20% (w/w)), quantified to 72% to 88% 
betulin. Extraction solvent: n-Heptane. 
 
Triamcinolone acetonide 

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IRB Number: 21-091 A(10) 
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Triamcinolone acetonide is a derivative of prednisolone with high glucocorticoid activity and 
low mineralocorticoid activity. Triamcinolone acetonide is the acetonide salt form of 
triamcinolone, a topical synthetic corticosteroid with anti-inflammatory, antipruritic, and 
vasoconstrictive properties. Triamcinolone acetonide exerts its effect by binding to 
cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor– 
mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, 
with inhibition of synthesis of certain inflammatory mediators. Specifically, triamcinolone 
acetonide appears to induce phospholipase A2 inhibitory proteins, thereby controlling the 
release of the inflammatory precursor arachidonic acid from membrane phospholipids by 
phospholipase A2. 
Because triamcinolone is fluorinated and also contains a substituted 17-hydroxyl group, it is 
not metabolized in the skin. Repeated application results in a cumulative depot effect in the 
skin, which may lead to a prolonged duration of action and increased systemic absorption. 
As circulating levels are below the level of detection, the use of pharmacodynamic endpoints 
for assessing the systemic exposure of topical triamcinolone is necessary. Once in the 
systemic circulation, triamcinolone is metabolized in the liver, but systemic metabolism has 
not been fully quantified. Excretion of triamcinolone acetonide and its metabolites occurs via 
the urine and bile. 
 
Molecular weight 
Oleogel-S10 
Betulin (main component): 442.73 g/mol 
Triamcinolone acetonide: 466.974 g/mol 
 
Formulation and excipients: 
Oleogel-S10 
Birch bark extract (TE): 10 mg/100 mg; Sunflower oil, refined: 90 mg/100 mg 
 
The extract with the oil forms a colorless to slightly yellowish, opalescent gel without any 
further ingredients. Oleogel-S10 is a gel with the active substance birch bark extract 
(triterpene extract, TE). 
 
Triamcinolone acetonide 
Triamcinolone acetonie is a colorless cream. 1 mg of Triamcinolone Acetonide per gram in a 
base containing Emulsifying Wax, Cetyl Alcohol, Isopropyl Palmitate, Sorbitol Solution, 
Glycerin, Lactic Acid, Benzyl Alcohol and Purified Water. 
Pharmaceutical Properties 
Oleogel-S10 
TE is a dry extract (refined) from Betulae cortex (birch bark) from Betula pendula Roth, 
Betula pubescens Ehrh. as well as hybrids of both species (yield 10-20% (w/w)), quantified to 
72% to 88% betulin (also called triterpene dry extract from birch bark). TE contains about 
90% of the triterpenoids betulin (72% to 88%), betulinic acid (0.5% to 6%), lupeol (2% to 
8%), oleanolic acid (0.1% to 2%), and erythrodiol (0.5% to 2%). Numerous biological effects 

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IRB Number: 21-091 A(10) 
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are reported for these substances. Besides antibacterial, antimycotic, antiviral, anti- 
inflammatory effects and antitumour effects, the triterpenes also display wound healing- 
promoting effects. Oleogel-S10 is applied topically. The effects of TE were investigated by 
preclinical in vitro and in vivo studies as well as by clinical phase 2 and 3 studies in different 
indications, including a phase 2 study in epidermolysis bullosa (EB). 
Non-clinical Studies 
Parenteral 14- and 28-day repeated dose toxicity studies in rats and dogs, respectively, 
showed no systemic test substance related changes except for those expected due to the 
insolubility of the TE extract at the injection site. Dermal application to intact or abraded 
minipig skin did not result in any systemic toxicity or adverse local reactions in a 4-week local 
tolerability study. A 39-week study in 24 Göttingen minipigs to measure the dermal safety of 
Oleogel-S10 versus sunflower oil control and sham-treated animals following daily non- 
occlusive administration to intact skin representing 10% of the body surface area, is ongoing. 
An interim report at 3-months indicates no significant treatment-relate findings including the 
analysis from skin biopsies taken at this timepoint. Systemic toxicity was assessed in juvenile 
rats following daily oral administration (by gavage) of TE in sunflower oil. The objective of this 
GLP study was to investigate the potential toxicity once daily from Day 10 to at least Day 63 
of age, inclusive, and to assess the reversibility of any observed effects over a 28-day 
treatment-free period. Significant systemic exposure was achieved although both Cmax and 
AUC were lower at Day 63 due to differences in absorption by the immature and mature 
intestinal tract. At the doses tested (30, 100 or 300 mg/kg/day) TE was well tolerated, with no 
adverse effect on growth or development. For the females, minimal to moderate periportal 
vacuolation was seen in the liver at all dose levels, which was considered not to be adverse 
as the change typically reversed after a 28-day treatment-free period and there were no 
corresponding liver enzyme changes in the females. Based on the above findings in these 
juvenile animals, the No Observed Adverse Effect Level (NOAEL) was considered to be 300 
mg/kg/day. At this dose, mean total systemic exposure (AUC0-24) of betulin, the primary 
component of TE, on Day 63 of age was 3,140 ng.h/mL and 2,110 ng.h/mL in males and 
females, respectively far in excess of any systemic exposure anticipated in the clinical study. 
A further 6-month systemic toxicity study in adult rats is currently ongoing. A study to 
investigate the effects of systemic exposure of TE on fertility and early embryonic 
development was completed and showed there was no negative impact when TE was 
delivered orally. Additionally, Oleogel-S10/TE did not act as a sensitiser, was not phototoxic, 
and was negative in all genotoxicity studies. 
Clinical Studies 
A phase 2 study in EB patients (12 wounds of 10 patients) (Schwieger-Briel 2017), as well as 
observations in 4 additional single case reports suggest that Oleogel-S10 may accelerate the 
healing of EB partial thickness wounds. Oleogel-S10 was well tolerated and no adverse drug 
reactions were observed. That Oleogel-S10 can accelerate the wound healing process was 
demonstrated in other wound types. In one phase 2 (24 patients) and three clinical phase 3 
trials (280 patients) in partial thickness wounds, Oleogel-S10 showed a faster healing than 
standard treatment: in split-thickness skin graft donor site wounds the 17-day healing period 
with standard treatment was reduced by 1 to 2 days (Barret 2017), in Grade 2a burn wounds 
the 9-day healing period with standard treatment was reduced by 1 day. The studies 
compared intra-individually the difference in time to wound healing between wound halves 
treated with Oleogel-S10 versus wound halves treated with standard of care. The number of 
adverse events such as wound infections was lower on wound halves treated with Oleogel- 

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IRB Number: 21-091 A(10) 
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S10 compared to those treated with standard of care. The most frequently observed adverse 
reactions were wound complication (in 2.9% of patients), pain of skin (2.5%) and pruritus 
(1.3%). Adverse reactions were administration site reactions only. Clinical studies in further 
indications showed that TE was safe and well tolerated in atopic dermatitis (33 patients), 
psoriasis (24 patients), and actinic keratosis (151 patients). In summary, pharmacological 
data obtained with in vitro and in vivo model systems supports the potential utility of topically 
applied Oleogel-S10 in the treatment of grade 2 to 3 radiation dermatitis wounds. 
Triamcinolone acetonide 
Triamcinolone acetonide is indicated for the treatment of the following: moderate-to-severe 
inflammatory manifestations (including pruritus), corticosteroid-responsive dermatologic 
disorders (such as alopecia areata), atopic dermatitis, contact dermatitis, generalized 
exfoliative dermatitis, Rhus dermatitis (caused by plants such as poison ivy), seborrheic 
dermatitis, eczema (including severe hyperkeratotic eczema, severe nummular eczema, and 
severe eczematous conditions of the hands or feet), granuloma annulare, keloids, cutaneous 
lichen planus, lichen simplex chronicus, lichen striatus, subacute cutaneous and discoid 
lupus erythematosus, pretibial myxedema, necrobiosis lipoidica diabeticorum, pemphigoid, 
pemphigus, pityriasis rosea, sarcoidosis, sunburn, and urticaria. 
 
Labeling: Medication labels will comply with US legal. They will supply no information about 
the patient. The same storage conditions will be described on each medication label. 
5.2 Drug supply and storage 
The drug will be shipped by Amryt Pharma directly to the MSKCC pharmacy. It will be 
received by a designated person at the MSKCC pharmacy, handled and stored properly and 
safely, and kept in a secured location to which only the investigator/pharmacist and/or 
designated assistants will have access. Upon receipt, Oleogel-S10 and vehicle gel should be 
stored according to the instructions specified on the drug labels [Store at below 30°C (86°F)]. 
Study tubes will be coded (no identifiable information regarding contents of vehicle or 
Oleogel-S10); both vehicle and Oleogel-S10 will have similar texture and color and will be 
indistinguishable. 
 
Triamcinolone acetonide should be stored according to the instructions specified on the drug 
labels. At the baseline visit, patients will receive a calculated number of tubes of Oleogel-S10 
gel or vehicle gel and one 454g jar of of triamcinolone acetonide 0.1% cream (standard of 
care). Additional jar(s) will be made available to the patients as needed, after they have used 
up the initial jar (as per study instructions) and returned the empty container to the study 
staff. Topical Triamcinolone are stored at 20° to 25°C (68° to 77°F) [See USP Controlled 
Room Temperature] 
These instructions will also be made clear to the patient for storage and self-administration of 
Oleogel-S10 or Vehicle placebo gel at home (Patient Information Sheet, Appendix IV). At 
visits 1-3, a 7-day supply of study drug will be dispensed. Daily dose is 0.002 gram per cm2 
of acute radiation dermatitis; total dispensed drug dose is 0.014 gram/cm2 x  
cm2 of acute 
radiation dermatitis. 
5.3 Study drug compliance 

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Compliance will be assessed by the investigator and/or study personnel at each patient visit 
using information provided by the patient and/or caregiver in the Medication Application Diary 
(Appendix V). This record will capture information of medication used, dosages administered, 
and intervals between visits and the completion of the study. Patient is required to bring the 
investigational medication tubes to study visits for drug diary review and drug accountability 
return. 
5.4 Medication administration 
All participants will initiate treatment within 3 days of informed consent/ registration 
(exceptions can be made per PI discretion); first day of medication application will be 
considered Study Day 1. 
Oleogel-S10 gel administration 
The Oleogel-S10 gel will be self-administered once daily in the evening for the Oleogel-S10 
group for the entire course of treatment by the patient (or caregiver), as per the instructions 
provided. The gel is applied to the wound surface at a thickness of approximately 1 mm and 
covered by Mepilex® Transfer dressing when possible. The gel is to be re-applied at each 
evening wound dressing change, until the wound is healed. 
 
Fresh wounds should achieve hemostasis prior to application of Oleogel-S10. If necessary, 
wounds should be cleaned according to standard procedures, using e.g.gentle soap and 
water, prior to application of Oleogel-S10. 
Oleogel-S10 gel is in tubes for single use only such that a new tube should be opened for 
each dressing change. Once opened, the product should be used immediately. Used tubes 
will be returned at following study visit for accountability. 
Vehicle gel administration 
The vehicle gel will be self-administered once daily in the evening for the placebo group for 
the entire course of treatment by the patient (or caregiver), as per the instructions provided. 
The gel is applied to the wound surface at a thickness of approximately 1 mm and covered 
by Mepilex® Transfer dressing when possible. The gel is to be re-applied at each evening 
wound dressing change, until the wound is healed. 
 
Fresh wounds should achieve hemostasis prior to application of vehicle. If necessary, 
wounds should be cleaned according to standard procedures, using e.g.gentle soap and 
water, prior to application of vehicle. 
Vehicle gel is in tubes for single use only such that a new tube should be opened for each 
dressing change. Once opened, the product should be used immediately. Used tubes will be 
returned at following study visit for accountability. 
Triamcinolone 0.1% cream administration 
Triamcinolone 0.1% cream will be self-administered once daily in the morning in both patient 
groups for the entire course of treatment by the patient (or caregiver), as per the instructions 
provided. The cream is applied to the wound surface at a thickness of approximately 1 mm 
and covered by Mepilex® Transfer. The cream is to be re-applied at each morning wound 
dressing change, until the wound is healed. 

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Page 14 of 37 
 
 
5.5 Supportive care guidelines and concomitant medications 
 
Participants must be instructed not to apply any (new) topical additional medications, 
including over-the-counter products during the trial without prior consultation with the 
investigator. All topical products applied to the skin within 14 days of screening should be 
recorded. This includes all moisturizers, sunscreen, sunblock etc. If concomitant therapy 
must be added or changed, including over-the-counter medications, or alternative therapies, 
the reason and name of the drug/therapy should be recorded by the investigator. 
 
6.0 
CRITERIA FOR PARTICIPANT ELIGIBILITY 
Any patients age 18 years and older with breast cancer undergoing post-mastectomy 
radiation therapy (PMRT) or post-lumpectomy RT will be considered for participation. 
6.1 
Participant Inclusion Criteria 
• 
Patients who are receiving PMRT to the chest wall or post-lumpectomy RT to the 
whole breast breast cancer of any stage 
• 
Age ≥ 18 years 
• 
Patients who develop ARD grade 2/3 after fraction day 20 (when receiving 25 total 
fractions) or after fraction day 25 when receiving (30 total fraction inclusive of a 5 
fraction boost) of radiation therapy with all locations of desquamation 
• 
Able to self-administer topical interventions or provide for another person to apply the 
topical intervention 
• 
Patients may be started on any topicals prior to study enrollment. Once patient is 
enrolled on study (on or before Day 1), patient must be able to discontinue other 
topicals (including topical steroids, Silvadene, calcineurin inhibitors) to the treatment 
area 
• 
Patients have completed surgery or chemotherapy ≥ 4 weeks prior to start of radiation 
therapy. Patients may receive antibody-drug conjugates at any time 
before/during/after study. 
• 
Women of childbearing potential (WCBP) must have a negative serum pregnancy test 
at Screening and a negative urine pregnancy test at Baseline (Day 0) and 
documented monthly. 
• 
WCBP must agree to abstrain from sex or use a highly effective method of birth 
control* from the time of consent through visit 5. 
 
*Adequate contraceptive methods include those with a low failure rate, i.e., less than 
1% per year, when used consistently and correctly, such as abstinence from sexual 
intercourse, and some double barrier methods (condom with spermicide) in 
conjunction with use by the partner of an intrauterine device, diaphragm with 
spermicide, oral contraceptives, birth control patch or vaginal ring, or injectable or 
implanted contraceptives. Abstinence is acceptable only as true abstinence: when 
this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence 

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Page 15 of 37 
 
 
(e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal 
are not acceptable methods of contraception. 
 
A woman that is postmenopausal (≥2 years since last menstrual period) or 
permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy) is 
not considered a WCBP. 
6.2 
Participant Exclusion Criteria 
• 
Patients who are receiving radiation therapy for inflammatory breast cancer or 
malignant fungating wound 
• 
Known history of allergy to any ingredient of the study medication 
• 
Patients with collagen-vascular disease/vasculitis 
• 
Patients receiving hypofractionated radiation therapy 
• 
Special populations: 
o patients who, in the opinion of the investigator have a condition that precludes 
their ability to provide an informed consent 
 
 
7.0 
RECRUITMENT PLAN 
A member of the patient’s treatment team, a protocol investigator, or research staff, at 
Memorial Sloan Kettering Cancer Center (MSKCC) will identify potential research subjects. If 
the investigator is a member of the treatment team, s/he will screen their patient’s medical 
records for suitable research study participants and discuss the study and their potential for 
enrolling in the research study. Potential subjects may also be referred to the 
investigator/research staff of the study by the treating physician or any MSKCC physician. 
Generally, the patient’s primary radiation oncologist and primary dermatologist will identify 
potential research subjects. 
The participating investigators may also screen the medical records of patients with whom 
they do not have a treatment relationship for the limited purpose of identifying patients who 
would be eligible to enroll in the study, and to record appropriate contact information in order 
to approach these patients regarding the possibility of enrolling in the study. 
The following procedure will be employed in enrolling all participants into the study. 
(Potentially) eligible patients identified by the mechanism described in the preceding 
paragraphs, will be offered participation in the study. This will be accomplished by the 
treating physician, clinician, or research staff, in person. The purpose of the study will be 
explained to the patient and informed consent will be obtained from willing participants. 
(Potential participants will also be offered the opportunity to consider participation and review 
the consent documents (e.g. at home) with the option of providing consent in the future.) 
Subsequently, a consenting professional will call potential adult study participants to invite 
them to participate. Patients may be screened by the research team at the patient’s location 
(e.g., in radiation oncology unit or dermatology unit). If they agree to enroll, then the eligible 

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Page 16 of 37 
 
 
participants will be scheduled for in-person consenting (if not already performed) and 
baseline assessments. The patient will be transferred to the dermatology clinic for enrollment 
and study assessments, when possible on the same day, or within the study window. This 
visit will preferably coincide with patients’ standard-of-care visit. Potential participants who 
decline participation will not be contacted again for the purpose of recruitment into the study. 
We will only retain participants’ basic information (e.g. questionnaire responses, eligibility 
checklist, etc.) that is needed for study reporting purposes. These records will be maintained 
on a secured Dermatology shared drive. We will also maintain a list of all participants 
approached throughout the entire study to record reasons for refusal and avoid re- 
approaching healthy volunteers that have been identified as ineligible or refusing 
participation. This list will be destroyed at the completion of the study. 
The investigators participating in this research include physicians and research staff from 
Memorial Sloan Kettering Cancer Center, as listed on the face page of this protocol, who 
have successfully completed training for protection of human research subjects in 
compliance with MSKCC clinical research policy. Written consent will be obtained by one of 
these individuals or his/her designee, who must also have successfully completed training for 
protection of human subjects in compliance with MSKCC clinical research policy. 
During the initial conversation between the investigator/research staff and the patient, the 
patient may be asked to provide certain health information that is necessary to the 
recruitment and enrollment process. The investigator/research staff may also review portions 
of their medical records at MSKCC in order to further assess eligibility. They will use the 
information provided by the patient and/or in the medical record to confirm that the patient is 
eligible, and to contact the patient regarding research enrollment. If the patient turns out to 
be ineligible for the research study, the study personnel will destroy all information collected 
on the patient during the initial conversation and medical records review, except for any 
information that must be maintained for screening log purposes. 
In most cases, the initial contact with the prospective subject will be conducted either by the 
treatment team, investigator or the research staff working in consultation with the treatment 
team. The recruitment process outlined presents no more than minimal risk to the privacy of 
the patients who are screened and minimal PHI will be maintained as part of a screening log. 
For these reasons, we seek a (partial) limited waiver of authorization for the purposes of (1) 
reviewing medical records to identify potential research subjects and obtain information 
relevant to the enrollment process; (2) conversing with patients regarding possible 
enrollment; (3) handling of PHI contained within those records and provided by the potential 
subjects; and (4) maintaining information in a screening log of patients approached (if 
applicable). 
7.1 
Research Participant Registration 
 
Confirm eligibility as defined in the section entitled Inclusion/Exclusion Criteria. Obtain 
informed consent, by following procedures defined in section entitled Informed 

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Consent Procedures. During the registration process registering individuals will be 
required to complete a protocol specific Eligibility Checklist. The individual signing the 
Eligibility Checklist is confirming whether or not the participant is eligible to enroll in 
the study. Study staff are responsible for ensuring that all institutional requirements 
necessary to enroll a participant to the study have been completed. See related 
Clinical Research Policy and Procedure #401 (Protocol Participant Registration). 
 
7.2 
Randomization 
This is a randomized double-blind label comparison of topical Oleogel-S10 versus 
vehicle gel, when added to standard of care (topical triamcinolone). After eligibility is 
established and immediately after consent is obtained, patients will be registered in 
the Clinical Trial Management System (CTMS). After registration, patients will be 
randomized in the Clinical Research Database (CRDB). Randomization will be 
accomplished by the method of random permuted block. Patients’ treatment 
assignments can be viewed in the CRDB only by CRDB staff. 
7.3 
Blinding 
The study will be conducted using a double-blind design. The randomization process 
that occurs on screening visit will blind the participant. The investigators will be 
unaware of the treatment assignment of participants unless unblinding is performed. 
7.4 
Unblinding 
Participant unblinding will be performed after all study assessments have been 
completed (after completion of Visit 6) by the PI only. The PI will seek MSK IRB 
approval prior to unblinding the participant. The study team will work with CRDB staff 
for unblinding after MSK IRB approves of it. Both the participant and the PI will be 
informed by CRDB personnel which arm the participant was randomized to. 
In case of emergency, emergency unblinding may be exercised when the PI believes 
that awareness of the subject's medication is beneficial to the management of the 
adverse event. When an emergency unblinding has taken place, the treatment 
identification information is only unmasked to the PI, and other personnel remains 
masked. The study team must discuss and receive approval from the PI before 
unblinding. Unblinding will be completed by contacting CRDB personnel. 
For participants whose treatment assignment has been unblinded due to emergency, 
the participant may continue the study treatment if the PI believes that the study 
medication is beneficial to the management of the patient’s wellbeing. 
 
 
8.0 
INFORMED CONSENT PROCEDURES 

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Before protocol-specified procedures are carried out, consenting professionals will explain 
full details of the protocol and study procedures as well as the risks involved to participants 
prior to their inclusion in the study. Participants will also be informed that they are free to 
withdraw from the study at any time. All participants must sign an IRB/PB-approved consent 
form indicating their consent to participate. This consent form meets the requirements of the 
Code of Federal Regulations and the Institutional Review Board/Privacy Board of this Center. 
The consent form will include the following: 
1. The nature and objectives, potential risks and benefits of the intended study. 
2. The length of study and the likely follow-up required. 
3. Alternatives to the proposed study. (This will include available standard and 
investigational therapies. In addition, patients will be offered an option of supportive 
care for therapeutic studies.) 
4. The name of the investigator(s) responsible for the protocol. 
5. The right of the participant to accept or refuse study interventions/interactions and to 
withdraw from participation at any time. 
Before any protocol-specific procedures can be carried out, the consenting professional will 
fully explain the aspects of patient privacy concerning research specific information. In 
addition to signing the IRB Informed Consent, all patients must agree to the Research 
Authorization component of the informed consent form. 
Each participant and consenting professional will sign the consent form. The participant must 
receive a copy of the signed informed consent form. 
 
9.0 
PRE-TREATMENT/INTERVENTION 
Patients may be screened and consented starting from up to 3 days before study initiation. 
The following initial baseline procedures can take place at any time during this period, or on 
the day of initiation: 
 
1. Medical history, including concomitant medications 
2. Study assessments (serve as baseline measures for the study): 
• 
Patient-reported Outcomes (Appendix): 
o PRO-CTCAE™ for acute radiation dermatitis wound 
o Radiation-induced skin reaction assessment scale (RISRAS) 
• 
Clinical assessments (Appendix) 
o Skin examination with calculation of surface area with ruler and 
device measurement of radiation dermatitis and wound 
o The radiation dermatitis will be graded according to the Common 
Terminology Criteria for Adverse Events (CTCAE) v5.0 
o Radiation-induced skin reaction assessment scale (RISRAS) 
• 
Standardized photography 

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o The affected area of chest including the acute radiation dermatitis 
wound including wound will be photographed. 
 
Visit # 
Study day: 
Pre-study Screening 
Day -3 to Day 1 
(In-Person) 
Reason for visit 
Informed consent 
X 
Medical history 
X 
Vital signs 
X 
Skin examination 
X 
Patient- and Physician- 
reported outcomes 
questionnaires PRO- 
CTCAE, CTCAE, and 
RISRAS 
X 
Standardized photography 
X 
Pregnancy test for women 
of childbearing potential 
X 
 
10.0 TREATMENT/INTERVENTION PLAN 
All patients will receive topical triamcinolone 0.1% cream application in the morning. Patients 
randomized to the Oleogel-S10 arm will be prescribed once nightly use of topical Oleogel- 
S10 gel and those randomized to the SOC arm will apply vehicle gel for 21 ± 2 days. 
Oleogel-S10 will be provided as topical gel. Triamcinolone 0.1% cream will be provided as a 
cream. 
Once daily (at least 60 minutes before bedtime), patients will be instructed to apply a 1 mm 
thick layer of the topical Oleogel-S10 gel to the area of acute radiation dermatitis. Patients 
will receive detailed instructions at the baseline visit and receive clear, written instructions on 
the standarized application technique (see Patient Information Sheet, Appendix IV). 
Approximately 0.1g of Oleogel-S10 or vehicle gel per cm2 of wound will be applied. Patients 
will be instructed to apply 1 fingertip unit (approximately 0.5g) per 250cm2 of wound. 
In the treatment group, patients will not be allowed to apply topical emollients to the treated 
area during the study, but if desired, they may apply to untreated areas. Patients will be 
advised not to use products with chemicals or perfumes. 
We do not anticipate the need for any adjustments to the treatment plan as consequence of 
adverse reactions to Oleogel-S10 (see section 15.0), but any patients with adverse 
cutaneous reactions to treatment with Oleogel-S10 will be advised to return to clinic to see a 

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IRB Number: 21-091 A(10) 
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Page 20 of 37 
 
 
dermatologist right away. Adverse event reporting will be based on CTCAE v5.0, as 
applicable. There will be six on-site visits. In the case of pandemic clinic closures, on-site 
visits may be converted to virtual visits in the case the patient does not have a same-day 
standard of care or treatment visit. 
Patients will also be asked to use a diary to improve their compliance with the application of 
triamcinolone 0.1% cream, Oleogel-S10 gel, vehicle gel, as well as to record fingertip units of 
study gel applied, any adverse effects of treatment, and will be asked to bring diaries to all 
patient visits. 
Skin examinations will be part of the evaluation performed during baseline visit at day 1, day 
7, day 14, day 21, day 49, and Day 168. Patients will also complete adapted PRO-CTCAE™ 
questionnaires to measure dermatology-specific patient-reported symptoms and outcomes at 
each of the aforementioned visits for the area of ARD. Study questionnaires should take the 
participant no more than 10 minutes to complete at each time point. Standarized 
photography will be performed day 1, day 7 ± 1 days, day 14 ± 2 days, day 21 ± 2 days, day 
49 ± 3 days, and Day 168 ± 7 days. Patients will be enrolled in the radiation oncology or 
dermatology clinics, and their clinical response will be assessed in the Dermatology clinic of 
Memorial Sloan-Kettering Cancer Center located in Manhattan or Basking Ridge. Visits Day 
1 and Day 14 will be in-person visits. Visits Day 7, 21, 49, and 168 may be conducted in- 
person or virtual per patient preference. 
Measurement of Wound Surface Area 
Wound surface area will be measured at each visit via Canfield Scientific, Inc, a HIPAA- 
compliant 3D imaging system that uses machine learning and computer vision to measure 
wounds. The Canfield software calculates the area once the user manually outlines the 
wound edge. Noncontiguous areas will each be outlined and the sum of the total area 
involved will be used. 3D Canfield photography is the gold standard wound imaging software 
for clinical trials. 
The investigator and authorized site study team members will receive a standardized training 
before start of the study. The ‘Photo Documentation Manual’ (Appendix) will provide a 
detailed description of the Canfield software, instructions for use, and a standard operating 
procedure of wound photography. 
Common Terminology Criteria for Adverse Events (CTCAE) v5.0 
The NCI Common Terminology Criteria for Adverse Events is a descriptive terminology 
which is routinely utilized for Adverse Event (AE) reporting in oncologic patients. A grading 
(severity) scale is provided for each AE term. 
PRO-CTCAE 
PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic 
toxicity in patients on cancer clinical trials. It was designed to be used as a companion to the 

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Common Terminology Criteria for Adverse Events (CTCAE), the standard lexicon for adverse 
event reporting in cancer trials. PRO-CTCAE provides a systematic yet flexible tool for 
descriptive reporting of symptomatic treatment side effects in cancer clinical trials. 
Radiation-induced Skin Reaction Assessment Scale (RISRAS) 
RISRAS is a tool developed for clinical and research practice with reliability and validity 
testing8. RISRAS measures both the subjective symptoms and objective signs of radiation- 
induced skin reactions8. This tool consists of a patient symptom scale for self-report and a 
healthcare professional assessment scale to measure the signs8. 
 
 
11.0 EVALUATION DURING TREATMENT/INTERVENTION 
Table 1. Assessments: 6 study visits 
Visit # 
1 
2 
3 
4 
5 
6 
Study Day 
Day -3 to 
Day 1*** 
(In-Person) 
Day 7 ± 1 
days 
(In-person or 
Virtual) 
Day 14 ± 
2 days 
(In-Person) 
Day 21 ± 2 
days 
(In-person or 
Virtual) 
Day 49 ± 
3 days 
(In-person or 
Virtual) 
Day 
168± 
7 
days 
(In- 
person or 
Virtual) 
Reason for 
visit 
Screening 
and Pre- 
treatment 
baseline 
evaluation 
Interval 
follow-up 
evaluation 
Interval 
follow-up 
evaluation 
Treatment 
ends 
Safety 
follow-up 
24- 
week 
Long- 
term 
follow- 
up 
Informed 
consent 
X 
Medical 
history 
X 
Vital signs 
X 
X 
X 
X 
X 
X 
Skin 
examination 
X 
X 
X 
X 
X 
X 
Pregnancy 
test for women 
of childbearing 
potential 
X 
X 
Patient- and 
Physician- 
reported 
outcomes 
questionnaires 
PRO-CTCAE, 
CTCAE, and 
RISRAS 
X 
X 
X 
X 
X 
X 

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Page 22 of 37 
 
 
 
Standardized 
photography 
with wound 
measurements 
X* 
X** 
X* 
X** 
X** 
X** 
Drug diary 
return 
X 
X 
X 
Drug 
accountability 
X 
X 
X 
Drug 
dispensed 
X 
X 
X 
Drug applied 
Begin on 
Day 1 
X 
X 
Completed 
this visit 
 
Footnotes: 
*Photos to be examined and measured via Canfield 3D imaging software 
**Photos to be examined and measured via Canfield 3D imaging software OR via Patient-Submitted 
Home Photos 
***Screening and Day 1 Visit can be combined to occur on the same date. 
 
12.0 CRITERIA FOR REMOVAL FROM STUDY 
Patients will be removed from the study (and will not be replaced) if: 
• 
They develop an adverse event necessitating discontinuation of topical interventions. 
• 
They develop a grade 2 or higher dermatologic adverse event that has an attribution by 
the investigator of at least ‘possibly’ treatment-related. 
• 
They require greater than 14 days off therapy due to a treatment-related adverse event. 
• 
They have RD progression to grade 4. 
• 
They develop new cutaneous metastases within the treatment area. 
 
Patients will be removed from the study and replaced if: 
• 
They enroll in an alternate systemic clinical trial which prohibits concurrent topical clinical 
trial participation. 
• 
They choose to withdraw consent for continued participation. 
• 
Death occurs unrelated to the RD. 
• 
They are lost to follow-up before RD can be evaluated. 
 
All patients who receive Oleogel-S10 or vehicle and report using the treatment will be 
evaluable for toxicity. 
 
13.0 
CRITERIA FOR OUTCOME ASSESSMENT AND ENDPOINT EVALUABILITY 
13.1 Criteria for Therapeutic Response/Outcome Assessment 
The primary outcome of this study is the efficacy of Oleogel-S10 in reducing radiation 
dermatitis grade 2-3 wound size in patient with breast cancer undergoing external 
beam radiation therapy. Clinical assessment at all study visits, including wound 

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surface area and adverse events will be performed by a dermatologist. Wound size 
will be measured using a HIPAA compliant 3D clinical imaging system. 
The following are the secondary outcomes: 
• 
Time to complete resolution of grade 2/3 radiation dermatitis assessed via 
standardized 3D clinical imaging. We will continue to monitor the study lesion 
area after the Day 14 (primary outcome) time point. Lesional area will monitored 
and imaged at all study visits through Day 168. A wound will be considered 
completely healed when wound size is 0 cm2. 
• 
Differences in adverse events at Day 21, as determined by the CTCAE v5.0; and 
health-related quality of life (HRQoL): as assessed by PRO-CTCAE (Appendix) 
and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS). 
The tertiary objectives of this study are to determine the effect of topical Oleogel-S10 
gel on the late effects of radiation, such as fibrosis, telangiectasias, 
hyperpigmentation, and dermatitis. 
 
 
Criteria for evaluation of clinical efficacy: 
Wound surface area: 
The PI or a trained designee will measure the subject’s wound and calculate surface 
area via the 3D Canfield Imaging Software for in person visits and via patient- 
submitted photographs for virtual visits, when applicable. 
 
Time to healing of wound: 
Wounds in both groups will be measured and photographed at baseline/Day 1, Day 7, 
Day 14, Day 21, Day 49, and Day 168. Measurements will be taken via Canfield 3D 
Imaging softwares on baseline/Day 1, Day 7*, Day 14, Day 21*, Day 49*, Day 168*. A 
wound will be considered healed when wound size is 0 cm2. (*Only for patients who 
present in person; otherwise wounds will be examined via patient-submitted home 
photos reviewed during virtual visit.) 
 
CTCAE Grading: 
Efficacy will be considered a mean improvement score in the CTCAE grade of each 
term of 0.3 or greater at Visit 5.The PI or a trained designee will assess the subject’s 
skin for adverse events and late effects for the below parameters using the CTCAE 
version 5.0 grading (severity) scale shown in Appendix I: 
o Dermatitis radiation 
o Body odor 
o Pain of skin 
o Pruritus 
o Skin hyperpigmentation* 

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o Skin hypopigmentation* 
o Dry skin 
o Skin atrophy 
o Hyperkeratosis 
o Skin induration (fibrosis) 
o Skin ulceration 
o Telangiectasia 
 
Note: A “0” grade will be used to document subjects with no presence of the CTCAE 
skin adverse event symptoms for radiation dermatitis, body odor, pain of skin, 
pruritus, skin hyperpigmentation, skin hypopigmentation, dry skin, skin atrophy, 
hyperkeratosis, skin induration, skin ulceration, telangiectasia. 
 
A percent body surface area for skin hyperpigmentation and skin hypopigmentation 
will be recorded and mean improvement will be calculated at visit 5. 
 
Subject Questionnaires: 
The subject will complete the below questionnaires for adverse events and late 
effects: 
• 
PRO-CTCAE questionnaire (see Appendix III) 
• 
Radiation-Induced Skin Reaction Assessment Scale (RISRAS) (see Appendix IIB) 
 
The PI or a trained designee will complete the below questionnaires for adverse 
events and late effects: 
• 
Radiation-Induced Skin Reaction Assessment Scale (RISRAS) (see Appendix) 
Patient Compliance: 
Study personnel will evaluate the patient diary for compliance with application of the 
topical Oleogel-S10 gel or placebo. If the patient diary is incomplete, the study 
participant will be asked about compliance since the last study visit. 
 
Criteria for evaluation of clinical safety: 
CTCAE Grading: 
Safety will be assessed by the PI or trained designee for adverse events, graded via 
the CTCAE v5.0. 
 
Breast cancer recurrence and survival 
Loco-regional recurrence and (disease-specific and overall) survival data will be 
collected through Visit 6 (24-week Long-term follow-up). We will explore differences in 
survival between the Oleogel-S10 and vehicle groups, controlling for stage of breast 
cancer at study treatment inception. 

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13.2 Criteria for Study Endpoint Evaluability 
The efficacy and tolerability analysis will be evaluated for all intent-to-treat subjects, 
defined as all subjects who use standard of care or Oleogel-S10 topical and have 
baseline and at least one post-baseline data point. 
In case of early subject withdrawal, subjects may be replaced based upon overall 
enrollment numbers. 
14.0 BIOSTATISTICS 
The primary objective of this study is to assess the efficacy of topical Oleogel-S10 gel vs 
placebo (vehicle gel) when added to standard of care (triamcinolone 0.1% cream) in reducing 
radiation wound surface area, when applied for 14 days to the radiated area of skin in 
patients with breast cancers and grade 2/3 dermatitis. For the primary objective we are 
measuring radiation wound size at baseline (day 1) and and follow-up (day 14 +/- 3 days). 
We are estimating percent change in radiation wound size between the two time points as: 
Percent change from baseline = (Baseline size – Follow-up size) x 100 
Baseline size 
 
A mean percent change will be estimated for both Oleogel-S10 and vehicle control arms. 
We plan to enroll and randomize 50 participants. If we lose ~10% of our participants between 
baseline and follow-up due to attrition, we will have an effective sample size of 44 
participants for primary endpoint evaluation. With 22 participants per treatment arm and an 
average percent reduction in the vehicle control arm of 0.2 or 20%, a common standard 
deviation of 0.2, and an alpha level of 5%; based on a two-sided means test we have >80% 
power to detect a mean difference of greater than 0.18 (Table). Estimates of percent 
reduction and standard deviation in the vehicle control arm were arrived at by the principal 
investigator’s experience treating these lesions in this patient population. To test the 
differences in mean percent change between the treatement groups at day 14, we will 
perform an independent sample Student’s t-test. 
 
 
 
 
 
Alpha- 
level 
Power 
N 
AP-101 
Vehicle 
Delta 
Average % 
change 
vehicle arm 
Average % 
change 
Oleogel- 
S10 arm 
Common 
SD 
0.05 
0.7364 
44 
22 
22 
0.16 
0.2 
0.36 
0.2 
0.05 
0.7865 
44 
22 
22 
0.17 
0.2 
0.37 
0.2 
0.05 
0.8305 
44 
22 
22 
0.18 
0.2 
0.38 
0.2 

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0.05 
0.8682 
44 
22 
22 
0.19 
0.2 
0.39 
0.2 
0.05 
0.8997 
44 
22 
22 
0.20 
0.2 
0.4 
0.2 
 
Secondary Objectives are to describe the resolution rate of grade 2/3 radiation- 
induced dermatitis. Evaluation of the safety of Oleogel-S10, and the patient reported 
symptoms will be assessed using the CTCAE v5.0 grading, the PRO-CTCAE 
(Appendix) and the Radiation-Induced Skin Reaction Assessment Scale (RISRAS). 
 
The efficacy of topical Oleogel-S10 gel vs placebo (vehicle gel) when added to standard of 
care (triamcinolone 0.1% cream) in reducing radiation wound surface area, when applied for 
21 days to the radiated area of skin in patients with breast cancers and grade 2/3 dermatitis 
will be assessed as a secondary outcome, with the above methods used for the primary 
outcome. 
Time to lesion resolution is defined as time from radiation therapy grade 2/3 dermatitis 
assessement to complete resolution of the radiation dermatitis. Assessments and 
quantification will be accomplished through the use of 3D clinical imaging for in-person visits 
and home photography for virtual visits. Patients with lesions that do not resolve at the time 
of study completion, or who are lost to follow-up, are to be censored at the last date of 
physician assessment and imaging. The proportion of patients who achieve resolution of the 
dermatitis will be calculated along with their 95% confidence intervals for both treatment 
arms. The rate of overall lesion resolution will be estimated by the Kaplan-Meier method. A 
logrank test will be used to compare the distributions of resolution rates by treatment arm. 
The rates of adverse events and the rates of grades 3-5 adverse events will be tabulated 
using the CTCAE v5.0. These adverse events will be presented on an individual basis and 
summarized using descriptive statistics. The proportion of patients with these toxicities and 
the severity will assessed at each study time point along with exact binomial confidence 
intervals. The proportion of pariticipants with adverse events by treatment group at each 
evaluation time point will be evaluated using chi-square statistics or Fisher’s exact tests. The 
distribution of patient-assessed Radiation-Induced Skin Reaction Assessment Scale 
(RISRSAS) scores will be assessed at each study time point. T-tests or Wilcoxon rank-sum 
tests will be used to assess differences in RISRAS scores. 
For the patient reported outcomes (PRO-CTCAE and RISAS) we will use descriptive 
statistics and graphical methods to show the measures at each time point and to display the 
the trends in these measures across the evaluation time points. For each intstrument, we will 
initially use ANOVA methods with repeated measures and a time component to assess 
whether there are any significant changes over time. If we observe significant changes, we 
will explore the subject-specific graphs to see if there is a consistent pattern in the changes 
(i.e., trending upward, trending downward, upward then levelling off, etc). We will also use 
random effects models to investigate any longitudinal associations. This method can 

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account for the serial correlation, time-varying covariates and missing interval measures from 
any of the study participants. 
We will invariably have some missing data during the course of the follow-up. We will try to 
determine whether these data are missing at random. With quality of life measures, patients 
with lower initial quality of life measures might be more prone to missingness. If we find a 
single missing quality of life instrument for a given time point for a participant, we will assume 
that this is missing at random. If we observe more than one missing instrument for a 
participant, we will attempt to determine whether refusal to complete the instrument is 
associated with disease severity and/or overall quality of life. If we see a general pattern of 
missingness within the study population, we will estimate the degree and direction to which 
this is occurring. 
As an exploratory objective, we will assess wound resolution in intertriginous vs non- 
intertriginous skin and with respect to radiation dose and late effects of radiation, such as 
fibrosis, telangiectasias, hyperpigmentation, and dermatitis. We will also characterize the 
timeline to onset of these AEs. The absolute number, distribution and the proportion of 
participants who experience these adverse events will summarized by study time point. The 
radiation dose to the skin will be recorded to evaluate if treatment hotspots impact dermatitis 
healing rates. We will record V110 to the skin of all patients enrolled on the trial 
retrospectively. The skin organ at risk volume will be defined as the 5mm from the patient 
surface encompassing the entire treatment portal. 
The analysis of this exploratory objective will be similar to the secondary objective with 
elapsed time to resolution of radiation dermatitis defined as time from radiation therapy grade 
2/3 dermatitis assessement to complete resolution of the radiation dermatitis. Lesions will be 
categorized as in intertriginous vs non-intertriginous by the study investigator based on visual 
skin examination at Study Day 1. Lesion resolution will be assessed by Canfield imaging. 
Patients with lesions that do not resolve at the time of study completion, or who are lost to 
follow-up, are to be censored at the last date of physician assessment and imaging. The 
proportion of patients who achieve resolution of the dermatitis will be calculated along with 
their 95% confidence intervals for both treatment arms and by categorization of intertriginous 
vs non-intertriginous areas. The rate of overall lesion resolution will be estimated by the 
Kaplan-Meier method. A logrank test will be used to compare the distributions of resolution 
rates by treatment arm and by intertriginous vs non-intertriginous areas. 
Patient compliance with the application of the topical Oleogel-S10 gel or placebo will be 
assessed at study visits 2, 3, & 4 (Day 7 +/-1 day, Day 14 +/- 2 days, & Day 21 +/- 2 days). 
For each pariticipant the total days compliant from Baseline to Day 21 will be summed. We 
will calculate the proportion of days compliant with application of topical Oleogel-S10 gel or 
placebo for each participant. We will also evaluate the distributions of compliance for the 
treatment and placebo arms, and compare mean or median compliance using a t-test or a 
Wilcoxon rank sum test. 

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15.0 TOXICITIES/RISKS/SIDE EFFECTS 
15.1 Oleogel-S10 
Safety 
Intensive non-clinical in vitro and in vivo experiments in different species of different 
ages and different routes of administration up to long-term chronic use raise no 
concerns for conducting clinical trials. In single and repeated dose experiments, in 
safety pharmacology tests, and in the genotoxic evaluation no adverse effects have 
been observed. Taking results of all toxicological experiments together, and keeping 
in mind that the intended route of TE is the Oleogel-S10 topical application, TE can, 
therefore, be considered as safe when applied to the skin, including abraded skin. In 
clinical trials in patients with partial thickness wounds Oleogel-S10 was well tolerated. 
The most common adverse events related to Oleogel-S10 concerned 25 patients out 
of 280 (9%), comprising pain of skin (2.9%) and pruritus (1.4%). 
 
Adverse Reactions Reported in Clinical Trials with Donor Site Wounds and Grade 2a Burns 
 
 
Deaths, serious adverse events and adverse events that led to discontinuation 
The number of patients in the pooled analysis (study BSH-12, BSG-12 and BBW-11) 
who experienced one or more serious AEs (SAEs) was low (15 or 5.4% of the 
patients). The most frequently reported SAEs were wound infection (4 or 1.4% of 
patients) and condition aggravated (2 or 0.7% of patients). All other SAEs were 
reported for 1 (0.4%) patient each. None was considered related to treatment except 
for one SAE (wound necrosis), for which causality between treatment and event was 
reported as “yes: unknown” by the investigator. Wound necrosis was experienced by 
a 79-year-old male in the Grade 2a burn wound study BBW-11 (Patient B-02-02). 
Both the wound half treated with Oleogel-S10 and the wound half treated with 
standard of care (Octenilin® wound gel with fatty gauze dressing) had changed to 
Grade 2b and required skin grafting resulting in prolonged hospital stay. A change in 
burn wound depth from Grade 2a to Grade 2b was expected for up to 30% of patients 
in the study. Skin grafting is the standard treatment for Grade 2b burn wounds. 

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No deaths were reported in the treatment phase of the studies. Two deaths in the 12 
months follow-up period were considered not related to the treatment. CTCAE 
Version 5 will be utilized for toxicity evaluation. 
 
15.2 Triamcinolone acetonide 
Topical application of triamcinolone acetonide cream results in a markedly (~90%) lower 
relative bioavailability than oral administration. Because triamcinolone is fluorinated and also 
contains a substituted 17-hydroxyl group, it is not metabolized in the skin. Repeated 
application results in a cumulative depot effect in the skin, which may lead to a prolonged 
duration of action and increased systemic absorption. As circulating levels are below the 
level of detection, the use of pharmacodynamic endpoints for assessing the systemic 
exposure of topical triamcinolone is necessary. Once in the systemic circulation, 
triamcinolone is metabolized in the liver, but systemic metabolism has not been fully 
quantified. Excretion of triamcinolone acetonide and its metabolites occurs via the urine and 
bile. 
Absorption after topical application of triamcinolone is increased in areas that have skin 
damage, inflammation, or occlusion or in areas where the stratum corneum is thin, such as 
the eyelids, genitalia, axillae, and face. The use of occlusive dressings with the application of 
triamcinolone enhances penetration into the skin and may increase the chance of systemic 
absorption. Ointments have a hydrating effect, are lipophilic, and enhance the penetration of 
triamcinolone into the skin. Triamcinolone gels, foams, and solutions also have enhanced 
topical penetration versus cream preparations. Once absorbed, maximal vasoconstrictive 
effects of triamcinolone occur within 1.5 hours of application. Anti-inflammatory effects are 
usually not seen for hours after triamcinolone application since the mechanism of action 
requires alterations in synthesis of proteins. 
Corticosteroid Hypersensitivity 
Triamcinolone is contraindicated in any patient with a history of corticosteroid hypersensitivity 
and hypersensitivity to triamcinolone or any ingredients in the preparation. Although true 
corticosteroid hypersensitivity is rare, patients who have demonstrated a prior 
hypersensitivity reaction to triamcinolone should not receive any form of triamcinolone. It is 
possible, although also rare, that such patients will display cross-hypersensitivity to other 
corticosteroids. It is advisable that patients who have a hypersensitivity reaction to any 
corticosteroid undergo skin testing, which, although not a conclusive predictor, may help to 
determine whether hypersensitivity to another corticosteroid exists. Such patients should be 
carefully monitored during and following the administration of any corticosteroid. 
Cushing’s Syndrome, Hepatic Disease, Hypothalamic-Pituitary-Adrenal (HPA) 
Suppression, Occlusive Dressing, Skin Abrasion 
Systemic absorption of topical corticosteroids has produced reversible HPA suppression 
and/or manifestations of Cushing’s syndrome in some patients. Triamcinolone acetonide has 

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been shown to suppress the HPA axis at doses as low as 2 g/day. Conditions that increase 
systemic absorption include application of high-potency corticosteroids, use over large 
surface areas, prolonged use, use in areas where the epidermal barrier is disrupted (i.e., skin 
abrasion), use in pediatric patients, use in patients with hepatic disease, and the use of an 
occlusive dressing. Triamcinolone acetonide preparations should not be used with occlusive 
dressings. Patients receiving large doses of a potent topical corticosteroid such as 
triamcinolone should be evaluated periodically for evidence of HPA axis suppression and 
manifestations of Cushing’s syndrome. If these effects are noted, an attempt should be made 
to withdraw the drug, to reduce the frequency of application, or to substitute a less-potent 
corticosteroid. Recovery of HPA axis function is generally prompt and complete upon 
discontinuation. Infrequently, signs and symptoms of withdrawal may occur, requiring 
supplemental systemic corticosteroids. 
Diabetes Mellitus 
Topical corticosteroids, including triamcinolone, should be used with caution in patients with 
diabetes mellitus. Exacerbation of diabetes may occur with systemic absorption of the topical 
corticosteroid. Use of topical corticosteroids may further delay healing of skin ulcers in 
diabetic patients. 
Pregnancy 
Triamcinolone should be used during pregnancy only if the potential benefit justifies the 
potential risk to the fetus. Topical corticosteroids, including triamcinolone, should not be used 
in large amounts, on large areas, or for prolonged periods of time in pregnant women. 
Guidelines recommend mild to moderate potency agents over potent corticosteroids, which 
should be used in short durations. Fetal growth restriction and a significantly increased risk of 
low birthweight have been reported with the use of potent or very potent topical 
corticosteroids during the third trimester, particularly when using more than 300 g. There are 
no adequate and well-controlled studies of the teratogenic effects from topical application of 
triamcinolone in pregnant women. Corticosteroids have been shown to be teratogenic after 
dermal, oral, and subcutaneous administration in animal studies. Triamcinolone has greater 
potency and, thus, greater teratogenic potential than other topical corticosteroids. After 
subcutaneous administration of triamcinolone acetonide to pregnant mice and rabbits, 
increased malformations, such as cleft palate and skeletal abnormalities, were observed. 
Fungal Infection, Herpes infection, Infection, Measles, Peripheral Vascular Disease, 
Varicella, Viral Infection 
The normal inflammatory response to local infections can be masked by triamcinolone. 
Application of topical corticosteroids to areas of infection, including tuberculosis of the skin, 
dermatologic fungal infection, and cutaneous or systemic viral infection (e.g., herpes 
infection, measles, varicella), should be initiated or continued only if the appropriate anti- 
infective treatment has been instituted. If the infection does not respond to the antimicrobial 
therapy, the concurrent use of the topical corticosteroid should be discontinued until the 

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infection is controlled. Topical corticosteroids may delay the healing of noninfected wounds, 
such as venous stasis ulcers. Triamcinolone preparations should be used with caution in 
patients with markedly impaired circulation or peripheral vascular disease; skin ulceration 
has been reported in these patients following topical corticosteroid use. 
Geriatric, Skin Atrophy 
Topical corticosteroids should be used for brief periods or under close medical supervision in 
patients with evidence of preexisting skin atrophy. Geriatric patients may be more likely to 
have preexisting skin atrophy secondary to aging. Purpura and skin lacerations that may 
raise the skin and subcutaneous tissue from deep fascia may be more likely to occur with the 
use of topical corticosteroids in geriatric patients. Clinical trials of topical triamcinolone 
included insufficient numbers of elderly patients to perform a separate analysis of efficacy 
and safety in this population. On the basis of the available data, no dosage adjustments are 
required for elderly patients receiving topical triamcinolone. Use of lower-potency topical 
corticosteroids may be necessary in some patients. 
Adverse Reactions 
Previously observed adverse reactions for triamcinolone acetonide are listed below. 
Severe 
Skin atrophy / Delayed / 0-2.0 
Papilledema / Delayed / Incidence not known 
Increased intracranial pressure / Early / Incidence not known 
Visual impairment / Early / Incidence not known 
Ocular hypertension / Delayed / Incidence not known 
Moderate 
Erythema / Early / 1.0-10.0 
Withdrawal / Early / Incidence not known 
Pseudotumor cerebri / Delayed / Incidence not known 
Hyperglycemia / Delayed / Incidence not known 
Growth inhibition / Delayed / Incidence not known 
Hypothalamic-pituitary-adrenal (HPA) suppression / Delayed / Incidence not known 
Glycosuria / Early / Incidence not known 
Adrenocortical insufficiency / Delayed / Incidence not known 
Cushing's syndrome / Delayed / Incidence not known 
Hypertension / Early / Incidence not known 
Cataracts / Delayed / Incidence not known 
Impaired wound healing / Delayed / Incidence not known 
Skin ulcer / Delayed / Incidence not known 

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Tolerance / Delayed / Incidence not known 
Contact dermatitis / Delayed / Incidence not known 
Mild 
Maculopapular rash / Early / 1.0-10.0 
Pruritus / Rapid / 1.0-10.0 
Skin irritation / Early / 2.0-10.0 
Xerosis / Delayed / 1.0-10.0 
Striae / Delayed / 0-2.0 
Acneiform rash / Delayed / 0-2.0 
Infection / Delayed / 0-2.0 
Skin hypopigmentation / Delayed / 0-2.0 
Folliculitis / Delayed / 0-2.0 
Miliaria / Delayed / 0-2.0 
Hypertrichosis / Delayed / 0-2.0 
Telangiectasia / Delayed / 0-2.0 
Vesicular rash / Delayed / 0.3-0.3 
Ocular irritation / Rapid / 0.3-0.3 
Alopecia / Delayed / 0.3-0.3 
Headache / Early / 0.3-0.3 
15.3 
Serious Adverse Event (SAE) Reporting 
An adverse event is considered serious if it results in ANY of the following outcomes: 
• 
Death 
• 
A life-threatening adverse event 
• 
An adverse event that results in inpatient hospitalization or prolongation of existing 
hospitalization 
• 
A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• 
A congenital anomaly/birth defect 
• 
Important Medical Events (IME) that may not result in death, be life threatening, or 
require hospitalization may be considered serious when, based upon medical judgment, 
they may jeopardize the patient or participant and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition 
 
Note: Hospital admission for a planned procedure/disease treatment is not considered an 
SAE. 
 
SAE reporting is required as soon as the participant starts investigational 
treatment/intervention. SAE reporting is required for 30-days after the participant’s last 
investigational treatment/intervention. Any event that occur after the 30-day period that is 
unexpected and at least possibly related to protocol treatment must be reported. 

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Please note: Any SAE that occurs prior to the start of investigational treatment/intervention 
and is related to a screening test or procedure (i.e., a screening biopsy) must be reported. 
 
All SAEs must be submitted in PIMS. If an SAE requires submission to the HRPP office per 
IRB SOP RR-408 ‘Reporting of Serious Adverse Events’, the SAE report must be submitted 
within 5 calendar days of the event. All other AEs must be submitted within 30 calendar days 
of the event. 
The report should contain the following information: 
• 
The date the adverse event occurred 
• 
The adverse event 
• 
The grade of the event 
• 
Relationship of the adverse event to the treatment(s) 
• 
If the AE was expected 
• 
Detailed text that includes the following 
o A explanation of how the AE was handled 
o A description of the participant’s condition 
o Indication if the participant remains on the study 
• 
If an amendment will need to be made to the protocol and/or consent form 
• 
If the SAE is an Unanticipated Problem 
15.4 External SAE Reporting 
The SAE report should be completed as per above instructions. If appropriate, the report will 
be forwarded to the FDA by the IND Office 
 
15.5 Reporting to Amryt Pharma 
Reporting of Serious Adverse Events: Within 5 days of first awareness of the event, the 
Investigator will report to Amryt by email to medinfo@amrytpharma.com any Serious 
Adverse Event (“SAE,” as defined above) for which reporting is required under this provision. 
SAEs are to be reported for (1) Study subjects who are assigned or, in the case of a blinded 
Study, possibly assigned to receive the Amryt Product. The Principal Investigator should 
report an SAE as soon as it is determined to meet the definition, even if complete information 
is not yet available. 
Lack of Effect: Even though there may not be an associated SAE, lack of effect of the Amryt 
Product may be reportable. As used in this Agreement, the term SAE will be understood to 
include reportable instances of lack of effect. 
Reporting form to be used: MSKCC SAE form 

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Follow-up information: Investigator will assist Amryt in investigating any SAE and will provide 
any follow-up information reasonably requested by Amryt. 
Regulatory Reporting: Reporting an SAE to Amryt does not relieve the investigator of 
responsibility for reporting it to FDA or other appropriate Regulatory Authorities as required. 
 
Reporting of non-serious adverse events: Non-serious adverse events can be sent to Amryt 
at the end of the study when all data has been compiled and analysed. 
 
Occupational exposure: Due to the low risk profile of the drug being used in this study, MSK 
staff working with and around the study drug will follow all routine procedures, precautions 
and reporting of exposure. 
 
16.0 PROTECTION OF HUMAN PARTICIPANTS 
Prior to the enrollment of each patient, the risks, benefits and objectives of the study will be 
reviewed with the participant, including a discussion of the possible side effects. Patients 
reserve the right to withdraw participation from this study at any time. 
Risks: It’s unlikely that significant risks will be associated with the limited use of topical 
Oleogel-S10 and topical triamcinolone planned in this study. 
Benefits: The early use of topical Oleogel-S10 is hypothesized to wound size of acute 
radiation dermatitis with a positive safety profile. This would serve as a novel topical therapy 
for management of acute radiation dermatitis wounds and would improve patients’ symptoms 
during treatment. Prophylactic and therapeutic topical corticosteroid (with triamcinolone) 
reduces severity of ARD and is standard of care. 
Possible toxicities/ adverse events: Adverse events are rare. 1- <10% of patients 
developed local application-site side effects with Oleogel-S10 including pruritus and skin 
pain. Local application–site side effects anticipated with topical triamcinolone include dry 
skin, erythema, pruritus, skin peeling, and irritation. These adverse events are not expected 
to necessitate treatment interruption. These adverse effects are not expected to necessitate 
treatment interruption. Systemic toxicities, including wound infection and GI events, are rare. 
Toxicities are elaborated in section 11.0 of this protocol. The investigators will use a 
standardized form to assess adverse events during the visits, as well as rare reactions that 
could be reported by the patient. 
Consent process: Participation in this protocol is voluntary. All patients will be required to 
sign a statement of informed consent, which must conform to MSKCC IRB guidelines. 
Costs: Patients will not be charged for protocol related costs 
Alternatives: There are no FDA-approved topical therapies for the treatment of acute 
radiation dermatitis wounds. 

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Confidentiality: Every effort will be made to maintain patient confidentiality. Research and 
hospital records are confidential. Patients’ names and any other identifying information will 
not be used in reports or publications resulting from this study. Other authorized agencies 
and appropriate personnel may review patient records as required. 
16.1 
Privacy 
MSK’s Privacy Office may allow the use and disclosure of protected health 
information pursuant to a completed and signed Research Authorization form. The 
use and disclosure of protected health information will be limited to the 
individuals/entities described in the Research Authorization form. A Research 
Authorization form must be approved by the IRB and Privacy Board (IRB/PB). 
The consent indicates that individualized de identified information collected for the 
purposes of this study may be shared with other qualified researchers. Only 
researchers who have received approval from MSK will be allowed to access this 
information which will not include protected health information, such as the 
participant’s name, except for dates. It is also stated in the Research Authorization 
that their research data may be shared with others at the time of study publication. 
 
16.2 
Data Management 
Data forms will be developed for recording all information pertinent to the 
observations and tests described in this protocol. All study data will be collected by an 
assigned data manager who will enter this information into MSK Medidata in a timely 
and accurate manner. All data and forms gathered for this study will be collected and 
stored in a secure location in facilities of the Dermatology Service. Regular meetings 
attended by the data manager and the Principal Investigators will be held to review 
study progress and to manage any difficulties encountered. 
The data manager will collect toxicity and self-reported compliance data via patient’s 
diaries and patient interviews. Adverse events, including all toxic effects related to 
treatment will be recorded individually according to toxicity date. 
 
All clinical photographs will be maintained in digital format in a computerized archive 
(DermagraphixTM). This system labels each clinical photograph with study subject 
MRN, lesion number, and photograph date. 
All patient data and questionnaires will be accessed on the Health Information 
System (HIS) and Mirror Dermagraphix database, which are password protected with 
user level access. All the data will be entered and maintained in MSK Medidata. 
 
Estimated time of accrual: 6 months 
Accrual Rate: 4 patients per month 
Time to complete study: 15 months 

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Final data sets for publication are required to be locked and stored centrally for 
potential future access requests from outside entities. 
16.3 
Quality Assurance 
Study personnel will generate monthly registration reports to monitor patient accrual 
and completeness of registration data. Routine data quality reports will be generated 
to access missing data and inconsistencies. Accrual rates, extent and accuracy of 
evaluations and follow-up will be monitored periodically throughout the study period 
and potential problems will be brought to the attention of the study team for 
discussion and action. 
 
Data quality and protocol compliance audits will be conducted by the study team on a 
regular basis throughout the study period. 
16.4 
Data and Safety Monitoring 
The Data and Safety Monitoring Plan utilized for this study must align with the MSK 
DSM Plan, where applicable. 
The Data and Safety Monitoring (DSM) Plans at Memorial Sloan Kettering were 
approved by the National Cancer Institute in August 2018. The plans address the new 
policies set forth by the NCI in the document entitled “Policy of the National Cancer 
Institute for Data and Safety Monitoring of Clinical Trials.” 
There are several different mechanisms by which clinical studies are monitored for 
data, safety and quality. At a departmental/PI level there exists procedures for quality 
control by the research team(s). Institutional processes in place for quality assurance 
include protocol monitoring, compliance and data verification audits, staff education 
on clinical research QA and two institutional committees that are responsible for 
monitoring the activities of our clinical trials programs. The committees: Data and 
Safety Monitoring Committee (DSMC) for Phase I and II clinical trials, and the Data 
and Safety Monitoring Board (DSMB) for Phase III clinical trials, report to the Deputy 
Physician-in-Chief, Clinical Research. 
During the protocol development and review process, each protocol will be assessed 
for its level of risk and degree of monitoring required. 
The MSK DSMB monitors phase III trials and the DSMC monitors non-phase III trials. 
The DSMB/C have oversight over the following trials: 
• 
MSK Investigator Initiated Trials (IITs; MSK as sponsor) 
• 
External studies where MSK is the data coordinating center 
• 
Low risk studies identified as requiring DSMB/C review 
The DSMC will initiate review following the enrollment of the first participant/or by the 
end of the year one if no accruals and will continue for the study lifecyle until there 

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are no participatns under active therapy and the protocol has closed to accrual. The 
DSMB will initiate review once the protocol is open to accrual. 
17.0 
REFERENCES 
1. 
Early Breast Cancer Trialists' Collaborative G, Darby S, McGale P, et al. Effect of 
radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast 
cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised 
trials. Lancet. 2011;378(9804):1707-1716. 
2. 
Ho AY, Olm-Shipman M, Zhang Z, et al. A Randomized Trial of Mometasone Furoate 0.1% 
to Reduce High-Grade Acute Radiation Dermatitis in Breast Cancer Patients Receiving 
Postmastectomy Radiation. Int J Radiat Oncol Biol Phys. 2018;101(2):325-333. 
3. 
Schwieger-Briel A, Ott H, Kiritsi D, Laszczyk-Lauer M, Bodemer C. Mechanism of Oleogel- 
S10: A triterpene preparation for the treatment of epidermolysis bullosa. Dermatol Ther. 
2019;32(4):e12983. 
4. 
Agency EM. Episalvan (International non-proprietary name: birch bark extract). 19 
November 2015 2015. 
5. 
Barret JP, Podmelle F, Lipovy B, et al. Accelerated re-epithelialization of partial-thickness 
skin wounds by a topical betulin gel: Results of a randomized phase III clinical trials program. 
Burns. 2017;43(6):1284-1294. 
6. 
Frew Q, Rennekampff HO, Dziewulski P, et al. Betulin wound gel accelerated healing of 
superficial partial thickness burns: Results of a randomized, intra-individually controlled, 
phase III trial with 12-months follow-up. Burns. 2019;45(4):876-890. 
7. 
Oleogel-S10 (AP101) in Epidermolysis Bullosa. Amryt Pharma; 31 October 2017 2017. 
8. 
Noble-Adams R. Radiation-induced skin reactions. 3: Evaluating the RISRAS. Br J Nurs. 
1999;8(19):1305-1312. 
 
 
18.0 
APPENDICES 
Appendix I: Modified CTCAE v5.0 
Appendix IIA: RISRAS for MD 
Appendix IIB: RISRAS for Patient 
Appendix III: PRO-CTCAE 
Appendix IV: Patient Information/Instructions Sheet 
Appendix V: Application Diary 
Appendix VI: Canfield 3D Imaging System Photo Documentation Manual