Modified Dakin's Solution in Reducing Radiation-Induced Dermatitis in Patients With Head and Neck Cancer Undergoing Radiation Therapy

• Sponsor: Stanford University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02369835
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 132
• Locations: 2
• Arms: 2
• Duration (Months): 38.6
• Patients Per Site: 66
• Patients Per Site Per Month: 1.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Carcinoma; Radiation-Induced Dermatitis	Drug: Dakin's solution; Other: Placebo	Phase 3

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

• 1. No skin change
• 1. Faint, barely detectable erythema
• 1. Follicular rash, hyperpigmentation, evolving erythema
• 1. Dry desquamation, brisk erythema
• 1. Moist desquamation
• 1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: A Randomized Study of Topical Dilute Hypochlorite (Modified Dakin's Solution) Treatment for the Prevention of Radiation Dermatitis in Head and Neck Cancer
• Study Start Date: May 1, 2015
• Actual Primary Completion Date: Jul 18, 2018
• Actual Study Completion Date: Jul 18, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I (modified Dakin's solution) 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.	Drug: Dakin's solution; Apply modified Dakin's solution (0.005 to 0.01%) topically; Other Names: Sodium hypochlorite in aqueous solution Dakin's fluid Liquid bleach
Placebo Comparator: Arm II (placebo) Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.	Other: Placebo; Applied topically; Other Names: PLCB

Outcome Measures

Primary Outcome Measures

1. Radiation Dermatitis [From first radiation treatment up to 10 weeks after completion of radiation treatment. Because much of the study data was not provided by the prior investigator to the current Responsible Party, it is not possible to be more precise than stated.]

   Participants were assessed for radiation dermatitis on the arms according to the Stanford Radiation Dermatitis Scoring System (SRDSS), at baseline and through their treatment course. The outcome is reported by treatment group as the number and proportion of participants that experience SRDSS Grade E or greater radiation dermatitis through 10 weeks after completion of radiation treatment, a number without dispersion. SRDSS, by grade: 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"

Secondary Outcome Measures

1. Time to Grade E Radiation Dermatitis [up to 12 weeks (estimated)]

   Participants were assessed for radiation dermatitis on the arms according to the Stanford Radiation Dermatitis Scoring System (SRDSS), at baseline and through their treatment course. The time that SRDSS Grade E radiation dermatitis developed was noted. The outcome is reported by treatment group as the mean time to development of SRDSS Grade E radiation dermatitis, with standard deviation. SRDSS, by grade: 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." Additional information describing this outcome is not available.

2. Pain Associated With Radiation Dermatitis [3 to 12 weeks after completion of radiation treatment]

   Quality of life was assessed as pain associated with radiation dermatitis. Assessments were baseline and through treatment follow-up 3 to 12 weeks after completion of radiation treatment. The assessment was to be conducted with a Modified Brief Pain Inventory (MBPI), a 13-question survey with responses ranging from 0 to 10, and an overall score of 0 to 130. A higher score indicates more pain and less quality of life. The outcome was to be reported by treatment group as the mean score with standard deviation. Additional information describing this outcome is not available.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Head and neck cancer who plan to undergo radiation therapy to the head and neck region

• At least 18 years of age

• Able to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior radiation therapy to the head and neck region or prior chemotherapy for head and neck cancer (induction chemotherapy NOT excluded)

• The physician-approved radiation treatment plan indicates a maximum prescription dose of less than 45 Gy

• Scleroderma or discoid lupus

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Cancer Center South Bay	San Jose	California	United States	95124
2	Stanford University School of Medicine	Stanford	California	United States	94305

Sponsors and Collaborators

• Stanford University
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Beth Beadle, Stanford University Hospitals and Clinics

Study Documents (Full-Text)

• Informed Consent Form - Apr 9, 2018
• Study Protocol and Statistical Analysis Plan - Jun 13, 2019

More Information

Publications

None provided.

• Responsible Party: Beth Beadle, Associate Professor of Radiation Oncology, Stanford University
• ClinicalTrials.gov Identifier: NCT02369835
• Other Study ID Numbers: IRB-32439; NCI-2015-00176; IRB-32439; ENT0042
• First Posted: Feb 24, 2015
• Last Update Posted: Sep 17, 2019
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Head and Neck Neoplasms; Dermatitis; Radiodermatitis; Sodium Hypochlorite; Eusol; Pharmaceutical Solutions

Study Results

Participant Flow

Arm/Group Title	Arm I (Modified Dakin's Solution)	Arm II (Placebo)
Arm/Group Description	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.	Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.
Period Title: Overall Study
STARTED	64	68
COMPLETED	53	55
NOT COMPLETED	11	13

Baseline Characteristics

Arm/Group Title	Arm I (Modified Dakin's Solution)	Arm II (Placebo)	Total
Arm/Group Description	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.	Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.	Total of all reporting groups
Overall Participants	64	68	132
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	29 45.3%	42 61.8%	71 53.8%
>=65 years	35 54.7%	26 38.2%	61 46.2%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	66 (11.6)	62 (12.7)	63.5 (12.3)
Sex: Female, Male (Count of Participants)
Female	10 15.6%	14 20.6%	24 18.2%
Male	54 84.4%	54 79.4%	108 81.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.6%	0 0%	1 0.8%
Asian	5 7.8%	9 13.2%	14 10.6%
Native Hawaiian or Other Pacific Islander	2 3.1%	0 0%	2 1.5%
Black or African American	1 1.6%	2 2.9%	3 2.3%
White	45 70.3%	49 72.1%	94 71.2%
More than one race	2 3.1%	1 1.5%	3 2.3%
Unknown or Not Reported	8 12.5%	7 10.3%	15 11.4%
Region of Enrollment (participants) [Number]
United States	64 100%	68 100%	132 100%
Baseline dermatitis (Count of Participants)
Count of Participants [Participants]	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Radiation Dermatitis
Description	Participants were assessed for radiation dermatitis on the arms according to the Stanford Radiation Dermatitis Scoring System (SRDSS), at baseline and through their treatment course. The outcome is reported by treatment group as the number and proportion of participants that experience SRDSS Grade E or greater radiation dermatitis through 10 weeks after completion of radiation treatment, a number without dispersion. SRDSS, by grade: 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"
Time Frame	From first radiation treatment up to 10 weeks after completion of radiation treatment. Because much of the study data was not provided by the prior investigator to the current Responsible Party, it is not possible to be more precise than stated.

Outcome Measure Data

Analysis Population Description

Not all participants completed radiation treatment, and are not included in the outcome.

Arm/Group Title	Arm I (Modified Dakin's Solution)	Arm II (Placebo)
Arm/Group Description	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.	Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.
Measure Participants	53	55
Count of Participants [Participants]	34 53.1%	36 52.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm I (Modified Dakin's Solution), Arm II (Placebo)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.8872
	Comments
	Method	Chi-squared
	Comments

2. Secondary Outcome

Title	Time to Grade E Radiation Dermatitis
Description	Participants were assessed for radiation dermatitis on the arms according to the Stanford Radiation Dermatitis Scoring System (SRDSS), at baseline and through their treatment course. The time that SRDSS Grade E radiation dermatitis developed was noted. The outcome is reported by treatment group as the mean time to development of SRDSS Grade E radiation dermatitis, with standard deviation. SRDSS, by grade: 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." Additional information describing this outcome is not available.
Time Frame	up to 12 weeks (estimated)

Outcome Measure Data

Analysis Population Description

Data for time to Grade E radiation dermatitis was not provided by the prior investigator to the current Responsible Party. On this basis, data is not available, and will never be available.

Arm/Group Title	Arm I (Modified Dakin's Solution)	Arm II (Placebo)
Arm/Group Description	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.	Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.
Measure Participants	0	0

3. Secondary Outcome

Title	Pain Associated With Radiation Dermatitis
Description	Quality of life was assessed as pain associated with radiation dermatitis. Assessments were baseline and through treatment follow-up 3 to 12 weeks after completion of radiation treatment. The assessment was to be conducted with a Modified Brief Pain Inventory (MBPI), a 13-question survey with responses ranging from 0 to 10, and an overall score of 0 to 130. A higher score indicates more pain and less quality of life. The outcome was to be reported by treatment group as the mean score with standard deviation. Additional information describing this outcome is not available.
Time Frame	3 to 12 weeks after completion of radiation treatment

Outcome Measure Data

Analysis Population Description

Data for pain associated with radiation dermatitis was not provided by the prior investigator to the current Responsible Party. On this basis, data is not available, and will never be available.

Arm/Group Title	Arm I (Modified Dakin's Solution)	Arm II (Placebo)
Arm/Group Description	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.	Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.
Measure Participants	0	0

Adverse Events

Time Frame	Duration of the study - from consent to the end of follow-up (follow-up visit 3 to 12 weeks after completion of treatment). Because much of the study data was not provided by the prior investigator to the current Responsible Party, it is not possible to be more precise than stated.
Adverse Event Reporting Description	Reported adverse events represent the entire set of adverse events as available to the current investigator and Responsible Party. There are no additional events available to report, and there never will be.
Arm/Group Title	Arm I (Modified Dakin's Solution)		Arm II (Placebo)
Arm/Group Description	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.		Participants apply placebo solution (saline) topically to the skin of the arm up to 3 hours in advance of each radiation treatment.
All Cause Mortality
	Arm I (Modified Dakin's Solution)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/64 (1.6%)		0/68 (0%)
Serious Adverse Events
	Arm I (Modified Dakin's Solution)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/64 (53.1%)		36/68 (52.9%)
Cardiac disorders
Cardiac arrest	1/64 (1.6%)	2	0/68 (0%)	0
Chest pain	0/64 (0%)	0	1/68 (1.5%)	1
Gastrointestinal disorders
Upper gastrointestinal hemorrhage	1/64 (1.6%)	2	0/68 (0%)	0
Mucositis	1/64 (1.6%)	1	0/68 (0%)	0
Colonic perforation	0/64 (0%)	0	1/68 (1.5%)	1
General disorders
Fever	1/64 (1.6%)	1	0/68 (0%)	0
Pain, shoulder pain	1/64 (1.6%)	2	0/68 (0%)	0
Infections and infestations
Sepsis	1/64 (1.6%)	1	0/68 (0%)	0
Meningitis	0/64 (0%)	0	1/68 (1.5%)	1
Injury, poisoning and procedural complications
Radiation dermatitis	34/64 (53.1%)	34	36/68 (52.9%)	36
Other, Foot ulcer	0/64 (0%)	0	1/68 (1.5%)	1
Respiratory, thoracic and mediastinal disorders
Other, shortness of breath	0/64 (0%)	0	1/68 (1.5%)	1
Aspiration, pneumonia	2/64 (3.1%)	2	0/68 (0%)	0
Skin and subcutaneous tissue disorders
Acneiform Rash	1/64 (1.6%)	1	0/68 (0%)	0
Surgical and medical procedures
Other, Feeding tube dysfunction	0/64 (0%)	0	1/68 (1.5%)	1
Other (Not Including Serious) Adverse Events
	Arm I (Modified Dakin's Solution)		Arm II (Placebo)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/64 (82.8%)		55/68 (80.9%)
Gastrointestinal disorders
Abdominal pain	0/64 (0%)	0	1/68 (1.5%)	1
Bloating	0/64 (0%)	0	1/68 (1.5%)	1
Mucositis	0/64 (0%)	0	1/68 (1.5%)	1
Nausea	0/64 (0%)	0	1/68 (1.5%)	1
General disorders
Fever	1/64 (1.6%)	1	0/68 (0%)	0
Injury, poisoning and procedural complications
Radiation dermatitis	53/64 (82.8%)	53	55/68 (80.9%)	55

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.