Clinical trial NCT02369835
Conditions: Head and Neck Carcinoma Radiation-Induced Dermatitis
Sponsor: Stanford University
Start date: 2015-05-01; Completion date: 2018-07-18
Enrollment: 132 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This randomized phase 3 trial studies how well modified Dakin's solution works in reducing radiation-induced dermatitis, a common skin reaction to radiation therapy, in patients with head and neck cancer undergoing radiation therapy. Modified Dakin's solution may reduce inflammation in the body, which may prevent or reduce dermatitis after radiation therapy.

Radiation therapy in this study is regulatory medical care based on the patient's needs and the radiation oncologist's judgment. It is not possible nor necessary to explicitly define the dose or duration of treatment.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the proportion of patients who develop grade 3 radiation dermatitis (as defined by the Stanford Radiation Dermatitis Scoring System) as an adverse effect of radiation therapy or chemoradiation therapy for a head and neck cancer when initiating the use of prophylactic hypochlorite (HOCl) (modified Dakin's solution) at the start of therapy (experimental arm) compared to placebo (control arm).

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I (EXPERIMENTAL): Participants apply modified Dakin's solution (0.005% to 0.010%) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.

ARM II (CONTROL): Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.

At the time that Stanford Radiation Dermatitis Scoring System (SRDSS) Grade E radiation dermatitis develops, the participant will transition to standard management for radiation dermatitis. SRDSS, by grade, is as follows.

* A. No skin change
* B. Faint, barely detectable erythema
* C. Follicular rash, hyperpigmentation, evolving erythema
* D. Dry desquamation, brisk erythema
* E. Moist desquamation
* F. Bleeding, ulceration, and/or infection

SRDSS Grade E is roughly equivalent to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03 Grade 3 radiation dermatitis, "Moist desquamation in areas other than skin folds and creases; bleeding induced by minor trauma or abrasion."

After completion of study, patients are followed up at 6 to 10 weeks.

Arms: arm 1: Participants apply modified Dakin's solution (0.005% to 0.010%) topically to the skin of the arm up to 3 hours in advance of each radiation treatment. arm 2: Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.
Interventions: intervention 1: Dakin's solution intervention 2: Placebo
Intervention descriptions: intervention 1: Apply modified Dakin's solution (0.005 to 0.01%) topically intervention 2: Applied topically

Protocol documents:
Prot_SAP_001.pdf: 
 
1 
 
A Randomized Study of Topical Dilute Hypochlorite (Modified Dakin’s Solution) Treatment  
for the Prevention of Radiation Dermatitis in Head and Neck Cancer 
 
Coordinating Center 
Stanford Cancer Institute 
875 Blake Wilbur Drive 
Stanford, CA 94305 
 
 
Co-Protocol Directors 
 
Beth Beadle, MD., Ph.D. 
Department of Radiation Oncology 
875 Blake Wilbur Drive, MC 5847 
Stanford, CA 94305 
Phone: (650) 723-6194 
Fax: (650) 725-8231 
bbeadle@stanford.edu  
 
 
 
 
Co-Investigators 
 
Quynh-Thu Le, MD 
Department of Radiation Oncology 
875 Blake Wilbur Drive, MC 5847 
Stanford, CA 94305 
Phone: (650) 723-6171 
Fax: (650) 725-8231 
qle@stanford.edu 
 
Susan Knox, MD, PhD 
Department of Radiation Oncology 
875 Blake Wilbur Drive, MC 5847 
Stanford, CA 94305 
Phone: (650) 725-2720 
Fax: (650) 725-8231 
sknox@stanford.edu
Bernice Yu Jing Kwong, MD 
Department of Dermatology 
900 Blake Wilbur Dr, W0071 MC 5334 
Stanford, CA 94305 
Tel: (650) 723-6316 
Fax: (650) 725-7711 
bernicek@stanford.edu 
 
 
 
 
 
 
 
 
 
 
 
Michael Gensheimer, MD. 
Department of Radiation Oncology 
875 Blake Wilbur Drive, MC 5847 
Stanford, CA 94305 
Phone: (925)-621-7700 
Fax: (650) 725-8231 
mgens@stanford.edu 
 
 
Alexander D. Colevas, MD 
Department of Internal Medicine 
Division of Medical Oncology 
875 Blake Wilbur Drive, MC 5826 
Palo Alto, CA 94305 
Phone: (650) 724-9707 
Fax: (650) 725-8231 


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colevas@stanford.edu 
 
 
Biostatistician 
 
Rie Von Eyben 
Department of Radiation Oncology 
875 Blake Wilbur Drive, MC 5847 
Stanford, CA 94305 
Phone: (650) 723-0914 
Fax: (650) 725-8231 
rieve@stanford.edu 
 
 
 
 
 
 
 
 
 
 
 
 
 
SRC Approved / Version 6 / June 13, 2019 


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TABLE OF CONTENTS 
 
PROTOCOL SYNOPSIS .............................................................................................................. 5 
SCHEMA ........................................................................................................................................ 6 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS (EXAMPLE) ....................... 7 
1. OBJECTIVES ......................................................................................................................... 8 
1.1 
PRIMARY OBJECTIVE .......................................................................................................... 8 
1.2 
SECONDARY OBJECTIVES ................................................................................................... 8 
2. BACKGROUND ..................................................................................................................... 8 
2.1 STUDY DISEASE ................................................................................................................... 8 
2.2 STUDY AGENT/DEVICE/PROCEDURE ................................................................................... 9 
2.3 STUDY DESIGN .................................................................................................................. 10 
3. PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES ........................ 10 
3.1 INCLUSION CRITERIA ......................................................................................................... 11 
3.2 EXCLUSION CRITERIA ........................................................................................................ 11 
3.3 INFORMED CONSENT PROCESS ........................................................................................... 11 
4. TREATMENT PLAN ........................................................................................................... 11 
4.1 DESCRIPTION OF TREATMENT PLAN .................................................................................. 11 
4.2 GENERAL CONCOMITANT MEDICATION AND SUPPORTIVE CARE GUIDELINES................... 12 
4.2 CRITERIA FOR REMOVAL FROM STUDY .............................................................................. 12 
4.3 ALTERNATIVES .................................................................................................................. 12 
5. STUDY AGENT/DEVICE/PROCEDURE INFORMATION .......................................... 12 
5.1 
 STUDY AGENT/DEVICE/PROCEDURE ................................................................................. 12 
5.2 AVAILABILITY ................................................................................................................... 12 
5.3 AGENT ACCOUNTABILITY .................................................................................................. 12 
6. DOSE MODIFICATIONS ................................................................................................... 13 
7. ADVERSE EVENTS AND REPORTING PROCEDURES ............................................. 13 
7.1 POTENTIAL ADVERSE EVENTS ........................................................................................... 13 
7.2 ADVERSE EVENT REPORTING ............................................................................................ 13 
8. CORRELATIVE STUDIES ................................................................................................ 14 
9. STUDY CALENDAR ........................................................................................................... 15 
10. MEASUREMENT .............................................................................................................. 16 
10.1  ASSESSMENT OF OUTCOME ............................................................................................. 16 
10.2  INTER-RATER RELIABILITY ............................................................................................. 16 
10.3  PRIMARY OUTCOME ........................................................................................................ 16 
10.4  SECONDARY OUTCOMES ................................................................................................. 17 
11. REGULATORY CONSIDERATIONS ............................................................................ 17 
11.1 INSTITUTIONAL REVIEW OF PROTOCOL ........................................................................... 17 
11.2 DATA AND SAFETY MONITORING PLAN ........................................................................... 17 
12. STATISTICAL CONSIDERATIONS .............................................................................. 17 
12.1 RANDOMIZATION METHOD …………………………………………………………….17 
12.2 SAMPLE SIZE JUSTIFICATION ........................................................................................... 18 
12.3 PRIMARY ANALYSIS ........................................................................................................ 18 
12.4 SECONDARY ANALYSIS ………...........................................................…………………18 
12.5 ACCRUAL ESTIMATES ...................................................................................................... 18 
12.6     INTER-RATER RELIABILITY TESTING................................................................................ 18 
12.7    CRITERIA FOR FUTURE STUDIES ....................................................................................... 18 
13. REFERENCES ................................................................................................................... 19 
APPENDICES .............................................................................................................................. 21 


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APPENDIX A: PARTICIPANT ELIGIBILITY CHECKLIST .................................................................. 21 
APPENDIX B: STANFORD RADIATION DERMATITIS SCORING SYSTEM ......................................... 23 
APPENDIX C: CTCAE VERSON 4.03 FOR RADIATION DERMATITIS ............................................. 24 
APPENDIX D: MODIFIED BRIEF PAIN INVENTORY ....................................................................... 25 
 


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PROTOCOL SYNOPSIS 
TITLE 
Randomized Study of Topical Dilute Hypochlorite for the 
Prevention of Radiation Dermatitis in Head and Neck Cancer 
STUDY PHASE 
Phase III 
STUDY REAGENT 
1:1000 dilute hypochlorite solution (0.005%) administered to the 
skin prior to daily radiation therapy 
PRIMARY OBJECTIVE(S) 
The primary objective is to determine whether prophylactic 
topical dilute HOCl reduces the proportion of patients who 
develop Grade E radiation dermatitis as scored on the Stanford 
Radiation Dermatitis Scoring System (SRDSS)  
SECONDARY 
OBJECTIVE(S) 
Secondary objectives are: 
- 
To determine whether this agent delays the time to 
development of Grade E radiation dermatitis 
- 
To determine whether this agent improves quality-of-life 
and pain scores associated with radiation dermatitis 
TREATMENT SUMMARY 
Eligible patients will be randomized to daily application of 
topical dilute hypochlorite versus placebo for 10 minutes within 3 
hours prior to daily radiation treatment. When patients in either 
arm develop Grade E radiation dermatitis during the radiotherapy 
course, they will be switched to topical dilute hypochlorite 
treatment daily per standard of care. Patients will complete the 
Modified Brief Pain Inventory at study entry, at 40-50 Gy 
through the radiation treatment course, at the end of radiation 
treatment, and at the follow-up visit 3-12 weeks after radiation 
treatment. 
SAMPLE SIZE  
170 Patients (85 patients per arm) 
STATISTICAL 
CONSIDERATIONS 
Sample Size Calculation: From prior clinical experience, we 
anticipate that 80% of patients will experience Grade E radiation 
dermatitis with standard skin care. In order to detect a 20% 
reduction in patients with Grade E dermatitis (80% vs 60% in 
those treated with dilute hypochlorite solution) with a two-sided 
alpha of 0.05 and beta of 80%, 170 patients will be enrolled.  
 
Primary endpoint: The proportion of patients in each arm who 
develop Grade E radiation dermatitis (as defined by the Stanford 
Radiation Dermatitis Scoring System) during a course of 
radiation therapy will be assessed using a multiple logistic 
regression model adjusting for type of chemotherapy (cisplatin, 
cetuximab, none). 
 
Secondary endpoints: Time to development of Grade E radiation 
dermatitis in each arm will be assessed using the Cox 
proportional hazards model adjusting for type of chemotherapy. 
QOL/Pain scores will be analyzed using a repeated measures 
model adjusting for type of chemotherapy. 
 
 


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SCHEMA 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
 
AE 
Adverse event 
CRF 
Case report/Record form 
CTCAE 
Common Terminology Criteria for Adverse 
Events 
DSMB 
Data Safety Monitoring Board 
HOCl 
Hypochlorite 
IRB 
Institutional Review Board 
MBPI 
Modified Brief Pain Inventory 
RR 
Response Rate 
SAE 
Serious adverse event 
SRDSS 
Stanford Radiation Dermatitis Scoring System 
 
 
 
 
 


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1. 
OBJECTIVES 
 
1.1. 
Primary Objective  
The primary objective is to determine the proportion of patients who develop Grade E radiation 
dermatitis (as defined by the Stanford Radiation Dermatitis Scoring System, See APPENDIX B) as an 
adverse effect of radiation therapy or chemoradiation therapy for a head and neck cancer when 
initiating the use of prophylactic HOCl at the start of therapy (experimental arm) compared to placebo 
(control arm). 
 
1.2. 
Secondary Objectives 
The secondary objectives include the time to development of Grade E radiation dermatitis and the 
quality-of-life and pain levels (as assessed by the Modified Brief Pain Inventory) in the control arm 
versus the experimental arm. 
 
 
2. 
BACKGROUND 
 
2.1 
Study Disease 
 
Radiotherapy is often used in combination with surgery and systemic therapy for the treatment of 
various malignancies. [1]. Although technological advances have allowed for more precision and 
accuracy in targeting malignant tissues, normal tissues unavoidably receive some radiation dose. For 
example, the skin overlying the target area receives incidental radiation, and up to 95% of patients can 
develop an acute reaction called radiation dermatitis [2, 3].  Radiation dermatitis develops when the 
skin is unable to repair itself in a timely manner upon repeated exposures to radiation [3-5]. Topical 
agents such as moisturizers, aloe vera, or corticosteroids can offer some relief of pain and irritation, 
however several randomized trials have demonstrated that they unfortunately do not prevent the onset 
of radiation dermatitis [1, 6-12]. For moderate-to-severe cases of radiation dermatitis, a break in the 
radiation treatment regimen is often required to allow time for the skin to heal. In addition to skin 
irritation and breakdown, patients can also experience significant pain and discomfort during this time. 
The only agent that has been shown in a randomized trial to significantly reduce the severity of skin 
reactions is a silicone dressing (Mepitel Film) [8]. While this was shown to reduce the incidence of 
moist desquamation in women undergoing radiotherapy treatments for breast cancer, it can cost up to 
$85 for a package of 10 dressings, making this type of treatment unaffordable for many patients [13]. 
Thus, significant improvements in the treatment of radiation dermatitis, a common side effect of 
radiation treatment, are needed. 
 
 
For patients with locally advanced head and neck cancer, chemoradiation has become standard of 
care [14-19]. Cisplatin is the standard agent for concurrent therapy; however, cetuximab, a molecular 
inhibitor of EGFR, is used as an alternative[20]. The addition of concurrent chemotherapy to radiation 
treatment has resulted in increased rates of Grade 3-4 radiation dermatitis ranging from 2-35% 
compared to 4-21% with radiation alone[14-20]. In addition, cetuximab is notorious for its significant 
skin toxicity and may potentiate radiation dermatitis as well with Grade 3-4 toxicity affecting 16-60% 
of patients undergoing concurrent treatment with radiation[21-23].  
 
 
Radiation dermatitis is typically scored using the CTCAE Scoring System. A severity of Grade 2 
indicates moist desquamation that is patchy or found in skin creases while Grade 3 indicates confluent 
moist desquamation away from skin creases. Moist desquamation in the head and neck region causes 
significant morbidity for patients: pain at the neck leading patients to alter their clothing at the neck 
line, inability to shower, lack of restful sleep, discomfort while eating, and feeling self-conscious when 


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being seen in public. There are multiple treatments for this complication, but practice varies by 
institution, and there is no established standard of care. 
 
 
2.2 
Study Agent and Rationale 
 
A standard treatment for radiation-induced moist desquamation (regardless of Grade 2 or Grade 3 
scoring by CTCAE) is dilute hypochlorite applied topically once or twice daily to the affected area. In 
this context, this treatment is given primarily for its antimicrobial properties. 
 
 
 
Recently, Leung et al discovered another potential mechanism of action for dilute hypochlorite 
baths [9]. HOCl functions as an oxidant and can disrupt cellular signaling processes by oxidizing 
certain mediators [24]. Nuclear factor-κB (NF-κB) is a protein complex that plays a central role in 
many different processes, including inflammation, aging, skin development, and radiation response 
[24]. Radiation injury activates NF-κB, which drives the cellular responses that can ultimately lead to 
radiation dermatitis [25, 26]. NF-κB plays a role in normal skin homeostasis as well [12-17]. NF-κB is 
also influenced by intracellular reduction-oxidation (redox) conditions [27]. NF-κB’s role in skin 
homeostasis and radiation injury suggests that it will be an attractive target for the treatment of 
radiation dermatitis. Because NF-κB is a master regulator of inflammation, we hypothesize that dilute 
hypochlorite baths may function as an anti-inflammatory agent by modulating NF-κB signaling and 
inflammatory responses in the skin [24]. 
 
 
 
 
Leung et al found that HOCl inhibits intracellular NF-κB signaling by oxidizing an upstream 
regulator without impairing global gene transcription and protein signaling.  In the skin of mice, a 
single brief exposure to topical HOCl significantly blocked NF-κB signaling. An established mouse 
model of radiation dermatitis was then used to assess whether hypochlorite could ameliorate acute 
radiation dermatitis. Radiation dermatitis was reproducibly induced on the backs of 4-week-old 
C57BL/6 female mice with 6 Gy irradiation for 10 days. Mice were randomized to receive a 30-minute 
bath in water (control) or dilute HOCl prior to each exposure to ionizing irradiation.  Skin was 
examined daily and assessed using Radiation Therapy Oncology Group (RTOG) criteria, which grades 
skin ulceration as the highest score (grade 4). Skin ulceration is defined as round excavations that 
result in the complete loss of epidermis and some portion of the dermis.  Compared to the control 
group, HOCl treated animals had a significantly lower RTOG score with scores of 1.8 ± 0.24 and 4.0 ± 
0 with and without HOCl treatment, respectively, by day 30.  While all control animals developed skin 
ulceration by day 20, none of the HOCl-treated animals developed skin ulceration even by day 30. 
Histological analysis of skin biopsies taken on day 14 revealed that the skin of irradiated control 
animals exhibited classical signs of radiation dermatitis, including a lichenoid infiltrate, loss of skin 
appendages, and epidermal/dermal swelling. In contrast, the skin of HOCl-treated animals was largely 
normal, with retention of skin appendages and a mild increase in dermal cellularity. Finally, irradiation 
of mice skin induced the expression of five well-established NF-κB–dependent genes, and HOCl 
exposure significantly diminished this response.  From clinical, histological, and molecular 
perspectives, it appeared that dilute bleach baths attenuated acute radiation dermatitis in mice. 
 
 
HOCl is a safe, well-characterized, inexpensive, and widely available topical agent. The rationale 
for the starting regimen of this study is based on the methods from the prior mouse work and prior 
published human studies. At dilute concentrations, hypochlorite is safe for human skin contact as 
demonstrated in a prior clinical trial using the same concentration [18].  Hypochlorite is stable under 
normal use and storage conditions [28]. It is a strong oxidizing agent and does react with household 
chemicals such as toilet bowl cleaners, rust removers, vinegar, acids, and ammonia containing products 


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to produce hazardous gases, such as chlorine and other chlorinated species [28]. Encounters with such 
products is not planned nor anticipated for this study. 
 
2.3 
Study Design 
This is a single-institution, randomized, double-blind, placebo-controlled clinical trial to 
investigate the role of topical HOCl in preventing radiation dermatitis in patients undergoing radiation 
therapy for head and neck cancer.  
 
Patients will be screened at the time of radiation oncology consultation. If eligible, patients will be 
offered participation and consented for enrollment. Per standard of care, simulation for radiation 
treatment and the treatment planning process will be performed over two weeks. Patients can be 
consented prior to or within 3 days following the start of radiation treatment. After consent, a baseline 
clinical skin assessment will be performed, and patients will be stratified by type of chemotherapy 
(cisplatin, cetuximab, or none) randomized to the control arm or the experimental arm. Randomization 
will be performed by the study coordinator and will not be disclosed to the patient or the treating 
physician. The experimental arm will apply daily topical dilute HOCl for 10 minutes within 3 hours 
prior to radiation treatment. The control arm will apply daily topical placebo (water) for 10 minutes 
within 3 hours prior to radiation treatment. Clinical skin assessments will be performed by the treating 
physician once weekly during the radiation treatment course per standard of care, and radiation 
dermatitis will be graded according to both the Stanford Radiation Dermatitis Scoring System and the 
CTCAE v4.03 Scoring System. On both study arms, when the patient develops Grade E radiation 
dermatitis per the Stanford Radiation Dermatitis Scoring System, defined as moist desquamation 
within the radiation treatment field, requiring treatment (not prophylaxis) with topical dilute HOCl, the 
patient will have met the endpoint of the study, and the patient will be switched to standard-of-care 
treatment for radiation dermatitis consisting of topical dilute HOCl applied daily. For patients who do 
not develop Grade E radiation dermatitis during the radiation treatment course, a final skin assessment 
will be performed +/- 10 days after the last day of radiation treatment. Photos of skin within the 
radiation treatment field will be taken at the time of each clinical assessment. In addition, enrolled 
patients will complete the Modified Brief Pain Inventory questionnaire at the time of randomization, at 
40-50 Gy of radiation treatment, on the last day of the radiation treatment course +/- 10 days, and at 
the follow-up visit 3-12 weeks after the completion of the radiation treatment course. 
 
There is currently no external sponsorship or funding for this protocol. 
 
2.3.1 Modified Brief Pain Inventory 
Patients with moderate-severe radiation dermatitis often experience significant pain and discomfort 
until the skin heals, which can sometimes take up to 2-3 weeks. In order to assess patient reported 
levels of pain, patients will be asked to complete the Modified Brief Pain Inventory (MBPI) at the time 
of randomization, at 40-50 Gy of treatment, on the last day of radiation treatment +/- 10 days, and at 
the first follow-up visit 3-12 weeks after completion of the radiation treatment course. The MBPI 
allows patients to rate the severity of their pain as well as the degree to which their pain interferes with 
normal activities. There are seven pain severity items and seven pain interference items rated on a 0-10 
Likert scale. It will take approximately 5 minutes to complete (ref; Appendix D). 
 
3. 
PARTICIPANT SELECTION AND ENROLLMENT PROCEDURES 
 Refer to the Participant Eligibility Checklist in Appendix A.  
 


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3.1 
Inclusion Criteria 
3.1.1 Patients with head and neck cancer who plan to undergo radiation therapy to the head and neck 
region 
 
3.1.2 Patients must be at least 18 years of age 
 
3.1.3 Patients must be able to understand and the willingness to sign a written informed consent 
document. A patient can be consented prior to or within 3 days following the start of 
radiation treatment. 
 
3.2 
Exclusion Criteria 
3.2.1 Prior external beam radiation therapy (EBT) to the head and neck region or prior chemotherapy 
for head and neck cancer (induction chemotherapy and I-131 treatment NOT excluded)c 
 
3.2.2 Patients whose physician-approved radiation treatment plan indicates a maximum prescription 
dose of less than 45 Gy 
 
3.2.3 Patients with scleroderma or discoid lupus 
 
3.3 
Informed Consent Process 
All participants will be provided a consent form describing the study with sufficient information for 
participants to make an informed decision regarding their participation. Participants will be required to 
sign the IRB approved informed consent prior to participation in any study specific procedure. The 
participant will receive a copy of the signed and dated consent document.  The original signed copy of 
the consent document will be retained in the medical record or research file.  
 
 
4. 
TREATMENT PLAN 
4.1 Description of Treatment Plan 
 
Patients will be screened for study eligibility by the research team when they arrive for their initial 
consultation for radiotherapy. If eligible and willing to participate, patients will sign informed consent 
and be enrolled in the study.  
 
Baseline 
 
 
Patients will undergo a clinical skin assessment by the treating physician. Patients will also 
complete the MBPI, and photographs will be taken of the neck to represent their baseline skin. Patients 
will be stratified by type of chemotherapy and randomized.   
 
During Radiation Therapy 
 
Prior to each radiation treatment, the study agent or placebo (depending on randomization arm) will be 
applied to the area of the skin to be irradiated for 10 minutes within 3 hours of the patient’s daily 
scheduled radiotherapy treatment. A nurse or qualified research member will instruct the patient on its 
application on the day of trial consent. After this initial instruction, the patient will self-apply the 
solution to their skin prior to treatment when he/she arrives to the radiation treatment area. There are 
clinic rooms that the patient can utilize to self-apply the solution prior to their daily radiation 
treatment. A nurse or qualified research member will check in with the patient once per week and 


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answer any questions if applicable. Patients will be instructed to use Vaseline as a moisturizer during 
the radiation treatment course per standard of care.  
 
A clinical skin assessment by the treating physician will be performed once weekly during the 
radiation treatment course and at the end of radiation treatment +/- 10 days. At each clinical skin 
assessment, skin toxicity will be graded using the Stanford Radiation Dermatitis Scoring System and 
the CTCAE Scoring System. Photographs will also be taken at 40-50 Gy of radiation treatment and at 
the end of radiation treatment +/- 10 days. 
 
Patients will also complete the Modified Brief Pain Inventory at the time of randomization, at 40-50 
Gy of radiation treatment, at the end of radiation treatment +/- 10 days, and at the follow-up visit 3-12 
weeks after the completion of the radiation treatment course. 
 
Follow Up 
 
During the patient’s follow up appointment 3-12 weeks after completion of the radiation treatment 
course, the patient will complete the MBPI, a clinical skin assessment will be performed, and 
photographs will be taken of their treatment area.  
 
4.2 
General Concomitant Medication and Supportive Care Guidelines 
There are no concerns for concomitant medications or additional treatments. Patients will undergo 
standard of care radiation therapy and the risks and guidelines will be appropriately discussed and 
outlined in person with the treating physician, in addition to the informed consent. Patients will 
continue standard skin care as recommended by their treating physician. 
 
4.3 
Criteria for Removal from Study 
Patients will be removed from the study if the patient experiences a severe allergic reaction in the 
treatment area and/or there is a significant worsening of dermatitis according to clinical assessment at 
the patient’s current radiotherapy dose. If the patient is removed from the study, they will no longer 
receive the study agent concurrently with their radiotherapy, however, they may continue to undergo 
radiotherapy per standard of care and clinical assessment. 
 
4.4 
Alternatives 
This study is optional. The alternative is to not participate in the study and receive standard radiation 
therapy without the study treatment.  
 
5. 
STUDY AGENT INFORMATION 
 
5.1 
 Study Agent  
The study agent is hypochlorite (HOCl) at a concentration of 0.0051%, otherwise known as modified 
Dakin’s solution. Clorox bleach will be diluted to attain this concentration. 
 
5.2 
Availability 
The dilute HOCl solution will be provided to the patient. 
 
5.3 
Agent Accountability 
The dilute HOCl solution will be stored in a locked cabinet in the Cancer Center. 


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6. 
DOSE MODIFICATIONS 
There will be no dose modifications during this study. Patients will be removed from the study if they 
experience a significant worsening of dermatitis according to clinical assessment at the patient’s 
current radiotherapy dose. The study agent will be discontinued and they will continue with 
radiotherapy alone and standard of care management for radiation dermatitis. 
  
7. 
ADVERSE EVENTS AND REPORTING PROCEDURES 
7.1 
Potential Adverse Events 
Potential risks associated with dilute HOCl are skin itching and skin irritation.  Prior human clinical 
trials demonstrated no significant risk of dilute 0.005% hypochlorite.  One patient had itching and mild 
skin irritation.  Because we are diluting the hypochlorite, we do not have significant concern for using 
concentrations that are too high. 
 
7.2 
Adverse Event Reporting 
Adverse events will be graded according to CTCAE v4.03 and Stanford Radiation Dermatitis Scoring 
System.  Both Serious and Non-Serious Adverse Events will be clearly noted in source documentation 
and listed on study specific Case Report Forms (CRFs).  The Protocol Director (PD) or designee will 
assess each Adverse Event (AE) to determine whether it is unexpected according to the Informed 
Consent, Protocol Document, or Investigator’s Brochure, and related to the investigation. All Serious 
Adverse Events (SAEs) will be tracked until resolution, or until 30 after the last dose of the study 
treatment.  
 
Skin-related SAEs CTCAE Grade 4 and above, and all subsequent follow-up reports will be reported 
to the Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) using the study 
specific CRF regardless of the event’s relatedness to the investigation. Following review by the 
DSMC, events meeting the IRB definition of ‘Unanticipated Problem’ will be reported to the IRB 
using eProtocol within 10 working days of DSMC review, or within 5 working days for deaths or life-
threatening experiences. 
 
 
8.  
CORRELATIVE STUDIES 
 
There will be no correlative studies involved in this investigation. 
 
 


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9. 
STUDY CALENDAR 
 
 
Baseline prior to 
Radiation 
Treatment 
During Radiation Treatment 
Follow-Up 
(3-12 weeks) 
Randomization 
X 
 
 
Blinded Solution 
Application 
(HOCl vs 
placebo) 
 
XA 
 
HOCl Treatment 
 
XB 
 
Clinical Skin 
Assessment 
X 
XC 
X 
QOL/Pain 
Questionnaire 
X 
XD, E 
X 
Photos of Neck 
X 
XD, E 
X 
 
A: Applied each day for 10 minutes within 3 hours of radiation treatment 
B: Starting at the onset of Grade E Radiation Dermatitis during radiation treatment, HOCl will be 
applied as treatment per standard of care for both study arms 
C: Performed once weekly by the treating physician and on the last day of radiation treatment +/- 10 
days 
D: Administered at 40-50 Gy of radiation treatment 
E: Administered on the last day of radiation treatment +/- 10 days


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10. 
MEASUREMENTS 
10.1 Assessment of Outcome 
Patients will be assessed on a weekly basis during radiation treatment as per standard of care. At each 
weekly on-treatment visit, a clinical skin assessment (physical exam) will be performed and 
documented per standard of care. 
 
In addition to standard management, all patients enrolled on this study will be required to have photos 
of the neck taken at four time points: at the time of randomization, at 40-50 Gy of radiation treatment, 
at the end of radiation treatment +/- 10 days, and at the follow-up visit 3-12 weeks after completion of 
radiation treatment. To ensure consistency, photos will be taken with standardized equipment. 
 
10.2 Inter-Rater Reliability 
 
Patients enrolled on this study will be treated by experienced radiation oncologists. Inter-rater 
reliability will be established by a run-in training session. Prior to opening the study for accrual, these 
physicians will undergo a training session for the grading of radiation dermatitis. The training session 
will involve the physicians’ review of 10 photos of the neck of patients undergoing treatment for head 
and neck cancer at various time points during treatment. Physicians will be blinded to the time point of 
the photo but will have access to the documented skin exam at the time the photo was taken. Each 
physician will assign a grade of radiation dermatitis for each photo, and the results will be assessed for 
reliability between the physicians with kappa statistics. A target kappa statistic of 0.8 will define good 
inter-rater reliability. If the target kappa statistic after the first set of photos is not met, the physicians 
will discuss and come to a consensus for each photo. A second set of 10 photos will then be assessed 
individually, and the kappa statistic will be again calculated. This process will be repeated for three 
iterations or until the target kappa score of 0.8 is met, whichever comes first. 
 
If the kappa statistic of 0.8 is not met, a jurisdiction will be held every three months during the accrual 
of the trial. The jurisdiction will involve both physicians reviewing every photo of every patient 
enrolled since the previous jurisdiction (or start of the trial in case of the first jurisdiction). For the 
photos on which there is disagreement, the physicians will meet to discuss and come to a consensus 
grade for each photo. The consensus grade will be recorded as the final grade for that photo. 
 
If the target kappa statistic of 0.8 is met and good inter-rater reliability is established, then spot-checks 
will be performed every three months during the accrual of the trial. A spot-check will involve the 
physicians assessing a set of the same 5 randomly-selected photos.  
 
10.3  Primary Outcome 
The primary outcome is the proportion of patients who experience Grade E radiation dermatitis as 
defined by the Stanford Radiation Dermatitis Scoring System in each arm of the study. 
 
10.3.1 Measurement Methods 
 
The primary outcome will be assessed and graded by the treating physician, a radiation oncologist, 
who will give an individual score of the irradiated area at baseline, once weekly during radiation 
treatment course, at the end of the radiation treatment course +/- 10 days, and at the patient’s follow up 
visit 3-12 weeks after completion of the radiation treatment course. The final grading of radiation 
dermatitis for each time point will be subject to the inter-rater reliability processes described in Section 
10.2. 
 


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10.4  Secondary Outcomes 
The secondary outcomes are to assess the time to development of Grade E radiation dermatitis and the 
quality of life and level of pain before, during, and after radiotherapy. 
 
10.4.1 Measurement Methods 
 
Patients will be seen once weekly during radiation therapy by the treating physician, who will perform 
the weekly clinical skin assessments. At the time Grade E radiation dermatitis develops, the study 
coordinator will be notified, and the patient will be switched to standard management for radiation 
dermatitis. 
 
The MBPI will be administered at the time of randomization, at 40-50 Gy of radiation treatment, at the 
end of radiation treatment +/- 10 days, and at the follow-up visit 3-12 weeks after completion of 
radiation treatment. 
 
11. 
REGULATORY CONSIDERATIONS 
11.1 
Institutional Review of Protocol 
The protocol, the proposed informed consent and all forms of participant information related to the 
study (e.g. advertisements used to recruit participants) will be reviewed and approved by the Stanford 
IRB and Stanford Cancer Institute Scientific Review Committee (SRC).  Any changes made to the 
protocol will be submitted as a modification and will be approved by the IRB prior to implementation.  
The Protocol Director will disseminate the protocol amendment information to all participating 
investigators. 
 
11.2 
Data and Safety Monitoring Plan 
The Stanford Cancer Institute Data and Safety Monitoring Committee (DSMC) will be the monitoring 
entity for this study. The DSMC will audit study-related activities to determine whether the study has 
been conducted in accordance with the protocol, local standard operating procedures, FDA regulations, 
and Good Clinical Practice (GCP).  This may include review of the following types of documents 
participating in the study: regulatory binders, case report forms, eligibility checklists, and source 
documents.  In addition, the DSMC will regularly review serious adverse events and protocol 
deviations associated with the research to ensure the protection of human subjects.  Results of the 
DSMC audit will be communicated to the IRB and the appropriate regulatory authorities at the time of 
continuing review, or in an expedited fashion, as needed. 
 
 
12. 
STATISTICAL CONSIDERATIONS 
 
12.1 
Randomization Method 
Block randomization will be used to stratify by type of chemotherapy: cisplatin, cetuximab, no 
chemotherapy. 
 
12.2 
Sample Size Justification 
The primary endpoint is the proportion of patients who develop Grade E radiation dermatitis (as 
defined by the Stanford Radiation Dermatitis Scoring System) in each arm during a course of radiation 
therapy. From prior clinical experience, we anticipate that 80% of patients will experience Grade E 
radiation dermatitis with standard skin care. In order to detect a 20% reduction in patients with Grade 
E radiation dermatitis (80% vs 60% in those treated with dilute hypochlorite solution) with Type I 
error of 0.05 and Type II error of 20% (power of 80%), 170 patients will be enrolled.  


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12.3 
Primary Analysis 
The primary endpoint is the proportion of patients who develop Grade E radiation dermatitis (as 
defined by the Stanford Radiation Dermatitis Scoring System) in each arm during a course of radiation 
therapy. A multiple logistic regression model will be used controlling for type of chemotherapy 
(cisplatin, cetuximab, none). 
 
12.4 
Secondary Analyses 
Secondary endpoints include the time to development of Grade E radiation dermatitis and the quality-
of-life and pain scores in each arm. Time to development of radiation dermatitis will be defined as time 
from Day 1 of radiation treatment to the first appearance of Grade E radiation dermatitis. This data will 
be summarized with Kaplan-Meier curves. A Cox proportional hazards model will be used to compare 
the treatment groups. The model will adjust for type of chemotherapy and other patient characteristics 
should they prove to be significant. A repeated measures model will be used to analyze the quality-of-
life and pain scores. The model will adjust for type of chemotherapy and other patient characteristics 
should they prove to be significant. 
 
12.5  Accrual Estimates 
 
 
We estimate that approximately 2 patients with head and neck cancer start radiation therapy in a given 
week in our department. Assuming that 2/3 of these patients would be eligible for this study and would 
provide consent with a 10% attrition rate, we estimate that this study will complete accrual of 170 
patients in 142 weeks (or 36 months). 
 
12.6 Inter-Rater Reliability Testing 
 
Inter-rater reliability will be evaluated using the kappa statistic. A kappa statistic of 0.8 will define 
good inter-rater reliability. For details of how this method will be implemented, see Section 10.2. 
 
12.7 
Criteria for Future Studies 
 
If our hypothesis is correct and the hypochlorite solution reduces the incidence of Grade E radiation 
dermatitis, we plan to initiate a multi-institution, phase III randomized clinical trial with the intention 
of establishing the prophylactic use of topical dilute hypochlorite solution as standard of care to 
prevent radiation dermatitis in patients undergoing radiation therapy for head and neck cancer. 


Protocol Version 6 
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13. 
REFERENCES 
 
1. 
Mitin T. Radiation therapy techniques in cancer treatment. In Basow DS (ed) UpToDate. 2014. 
2. 
Porock D, Nikoletti S, Kristjanson L. Management of radiation skin reactions: literature review 
and clinical application. Plast Surg Nurs 1999; 19: 185-192, 223; quiz 191-182. 
3. 
McQuestion M. Evidence-based skin care management in radiation therapy: clinical update. 
Semin Oncol Nurs 2011; 27: e1-17. 
4. 
Salvo N, Barnes E, van Draanen J et al. Prophylaxis and management of acute radiation-
induced skin reactions: a systematic review of the literature. Curr Oncol 2010; 17: 94-112. 
5. 
Ryan JL. Ionizing radiation: the good, the bad, and the ugly. J Invest Dermatol 2012; 132: 985-
993. 
6. 
Chan RJ, Larsen E, Chan P. Re-examining the evidence in radiation dermatitis management 
literature: an overview and a critical appraisal of systematic reviews. Int J Radiat Oncol Biol Phys 
2012; 84: e357-362. 
7. 
Fisher J, Scott C, Stevens R et al. Randomized phase III study comparing Best Supportive Care 
to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast 
irradiation: Radiation Therapy Oncology Group (RTOG) 97-13. Int J Radiat Oncol Biol Phys 2000; 
48: 1307-1310. 
8. 
Herst PM, Bennett NC, Sutherland AE et al. Prophylactic use of Mepitel Film prevents 
radiation-induced moist desquamation in an intra-patient randomised controlled clinical trial of 78 
breast cancer patients. Radiother Oncol 2014; 110: 137-143. 
9. 
Pinnix C, Perkins GH, Strom EA et al. Topical hyaluronic acid vs. standard of care for the 
prevention of radiation dermatitis after adjuvant radiotherapy for breast cancer: single-blind 
randomized phase III clinical trial. Int J Radiat Oncol Biol Phys 2012; 83: 1089-1094. 
10. 
Pommier P, Gomez F, Sunyach MP et al. Phase III randomized trial of Calendula officinalis 
compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J 
Clin Oncol 2004; 22: 1447-1453. 
11. 
Ryan JL, Heckler CE, Ling M et al. Curcumin for radiation dermatitis: a randomized, double-
blind, placebo-controlled clinical trial of thirty breast cancer patients. Radiat Res 2013; 180: 34-43. 
12. 
Williams MS, Burk M, Loprinzi CL et al. Phase III double-blind evaluation of an aloe vera gel 
as a prophylactic agent for radiation-induced skin toxicity. Int J Radiat Oncol Biol Phys 1996; 36: 345-
349. 
13. 
https://http://www.medicalmega.com/category/wound-
care/mepitel?ovchn=GGL&ovcrn=mepitel&ovtac=PPC&ovcpn=Broad&gclid=CIi0t5Dan70CFVKDfg
odq5YAMA. In. Medical Mega: 2014. 
14. 
Adelstein DJ, Li Y, Adams GL et al. An intergroup phase III comparison of standard radiation 
therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous 
cell head and neck cancer. J Clin Oncol 2003; 21: 92-98. 
15. 
Al-Sarraf M, LeBlanc M, Giri PG et al. Chemoradiotherapy versus radiotherapy in patients 
with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 
1998; 16: 1310-1317. 
16. 
Bernier J, Domenge C, Ozsahin M et al. Postoperative irradiation with or without concomitant 
chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350: 1945-1952. 
17. 
Calais G, Alfonsi M, Bardet E et al. Randomized trial of radiation therapy versus concomitant 
chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 
1999; 91: 2081-2086. 
18. 
Cooper JS, Pajak TF, Forastiere AA et al. Postoperative concurrent radiotherapy and 
chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004; 350: 
1937-1944. 


Protocol Version 6 
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19. 
Forastiere AA, Goepfert H, Maor M et al. Concurrent chemotherapy and radiotherapy for organ 
preservation in advanced laryngeal cancer. N Engl J Med 2003; 349: 2091-2098. 
20. 
Bonner JA, Harari PM, Giralt J et al. Radiotherapy plus cetuximab for locoregionally advanced 
head and neck cancer: 5-year survival data from a phase 3 randomised trial, and relation between 
cetuximab-induced rash and survival. Lancet Oncol 2010; 11: 21-28. 
21. 
Buiret G, Combe C, Favrel V et al. A retrospective, multicenter study of the tolerance of 
induction chemotherapy with docetaxel, Cisplatin, and 5-Fluorouracil followed by radiotherapy with 
concomitant cetuximab in 46 cases of squamous cell carcinoma of the head and neck. Int J Radiat 
Oncol Biol Phys 2010; 77: 430-437. 
22. 
Studer G, Brown M, Salgueiro EB et al. Grade 3/4 dermatitis in head and neck cancer patients 
treated with concurrent cetuximab and IMRT. Int J Radiat Oncol Biol Phys 2011; 81: 110-117. 
23. 
Suntharalingam M, Kwok Y, Goloubeva O et al. Phase II study evaluating the addition of 
cetuximab to the concurrent delivery of weekly carboplatin, paclitaxel, and daily radiotherapy for 
patients with locally advanced squamous cell carcinomas of the head and neck. Int J Radiat Oncol Biol 
Phys 2012; 82: 1845-1850. 
24. 
Leung TH, Zhang LF, Wang J et al. Topical hypochlorite ameliorates NF-kappaB-mediated 
skin diseases in mice. J Clin Invest 2013; 123: 5361-5370. 
25. 
Brach MA, Hass R, Sherman ML et al. Ionizing radiation induces expression and binding 
activity of the nuclear factor kappa B. J Clin Invest 1991; 88: 691-695. 
26. 
Pasparakis M. Role of NF-kappaB in epithelial biology. Immunol Rev 2012; 246: 346-358. 
27. 
Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen 
years later. Biochem Pharmacol 2006; 72: 1493-1505. 
28. 
The Clorox Company. In. Clorox Regular - Bleach [Material Safety Data Sheet] August 2009. 
 
 
 
 
 
 


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APPENDICES 
APPENDIX A: Participant Eligibility Checklist  
A Participant Eligibility Checklist must be completed in its entirety for each subject prior to 
registration. The completed, signed, and dated checklist must be retained in the patient’s study file and 
the study’s Regulatory Binder.  
 
The study coordinator, treating physician and an independent reviewer must verify that the 
participant’s eligibility is accurate, complete, and legible in source records. A description of the 
eligibility verification process should be included in the EPIC or other Electronic Medical Record 
progress note.  
 
Protocol Title: 
      
 
Protocol Number: 
 
Principal Investigator: 
Dr. Beth Beadle 
 
II. Subject Information: 
 
Subject Name/ID: 
 
Gender:    
 Male     
 Female 
III. Study Information: 
SRC Approved 
 IRB Approved 
 Contract signed 
 
IV. Inclusion/Exclusion Criteria 
 
Inclusion Criteria 
(From IRB approved protocol) 
Yes 
No 
Supporting 
Documentation* 
1. Patients with head and neck cancer 
who plan to undergo radiation 
therapy to the head and neck region 
 
 
      
2. Patient must be at least 18 years of 
age 
 
 
      
3. Ability to understand and the 
willingness to sign a written 
informed consent document 
 
 
      
Exclusion Criteria 
(From IRB approved protocol) 
 
1. Prior radiation therapy to the head 
and neck region or prior 
chemotherapy for head and neck 
cancer (induction chemotherapy 
NOT excluded) 
 
 
      
2. Maximum RX dose <45 Gy in the 
approved radiation treatment plan 
 
 
      
3. Patients with scleroderma or discoid 
lupus 
 
 
      
 
 
 


Protocol Version 6 
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*All subject files must include supporting documentation to confirm subject eligibility.  The 
method of confirmation can include, but is not limited to, laboratory test results, radiology test 
results, subject self-report, and medical record review.   
 
IV.  Statement of Eligibility 
By signing this form of this trial I verify that this subject is [
 eligible / 
 ineligible] for 
participation in the study. This study is approved by the Stanford Cancer Institute Scientific Review 
Committee, the Stanford IRB, and has finalized financial and contractual agreements as required by 
Stanford School of Medicine’s Research Management Group.   
 
 
 
Physician Signature: 
Date: 
Printed Name: 
 
 
Secondary Reviewer Signature: 
Date: 
Printed Name: 
 
 
Study Coordinator Signature: 
Date: 
Printed Name: 
 
 


Protocol Version 6 
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APPENDIX B: Stanford Radiation Dermatitis Scoring System 
 
 
Grade 
Clinical finding 
A 
No skin change 
B 
Faint, barely detectable erythema 
C 
Follicular rash, hyperpigmentation, evolving erythema 
D 
Dry desquamation, brisk erythema 
E 
Moist desquamation 
F 
Bleeding, ulceration, and/or infection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol Version 6 
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APPENDIX C: CTCAE Version 4.03 
 
Grade 
Clinical finding 
0 
No skin change 
1 
Faint erythema or dry desquamation 
2 
Moderate to brisk erythema; patchy moist desquamation, mostly confined to skin 
folds and creases; moderate edema 
3 
Moist desquamation in areas other than skin folds and creases; bleeding induced by 
minor trauma or abrasion 
4 
Life-threatening consequences; skin necrosis or ulceration of full-thickness dermis; 
spontaneous bleeding from involved site; skin graft indicated 
5 
Death 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Protocol Version 6 
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APPENDIX C: Modified Brief Pain Inventory 
 
Please fill in the following: 
First Name (1) 
Last Name (2) 
 
Time point for survey: 
 Baseline prior to radiation treatment (1) 
 40-50 Gy of radiation treatment (2) 
 Last day of radiation treatment (3) 
 Follow-up visit 3-12 weeks after radiation treatment course (4) 
 
Q1 Please rate your current level of skin discomfort. 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
 
Q2 Please rate your pain by selecting the one number that best describes your pain at its worst in the 
last 24 hours. 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q3 Please rate your pain by selecting the one number that best describes your pain at its least in the last 


Protocol Version 6 
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24 hours. 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q4 Please rate your pain by selecting the one number that best describes your pain on the average. 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q5 Please rate your pain by selecting the one number that tells how much pain you have right now. 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q6 What treatments or medication are you receiving for your pain? 
 
Q7 In the last 24 hours, how much relief have pain treatments or medications provided? Please select 


Protocol Version 6 
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the one percentage that most shows how much relief you have received? 
 0% (No Relief) (0) 
 10% (1) 
 20% (2) 
 30% (3) 
 40% (4) 
 50% (5) 
 60% (6) 
 70% (7) 
 80% (8) 
 90% (9) 
 100% (Complete Relief) (10) 
 
Select the one number that describes how, during the past 24 hours, pain has interfered with your: 
 
Q8 General Activity 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q9 Mood 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 


Protocol Version 6 
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Q10 Walking Ability 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q11 Normal Work (includes both work outside the home and housework) 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q12 Relations with other people 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 


Protocol Version 6 
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Q13 Sleep 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q14 Enjoyment of Life 
 0 (0) 
 1 (1) 
 2 (2) 
 3 (3) 
 4 (4) 
 5 (5) 
 6 (6) 
 7 (7) 
 8 (8) 
 9 (9) 
 10 (10) 
 
Q15 At this point, how much do you feel that this skin treatment will improve or prevent your skin 
discomfort during radiation treatment? (Asked only at baseline) 
 0% (No Relief) (0) 
 10% (1) 
 20% (2) 
 30% (3) 
 40% (4) 
 50% (5) 
 60% (6) 
 70% (7) 
 80% (8) 
 90% (9) 
 100% (Complete Relief) (10) 
 
Copyright 1991 Charles S. Cleeland, PhD Pain Research Group All Rights Reserved