Trial Title:
Dermatitis During Adjuvant Irradiation for BREAst Cancer:
NCT ID:
NCT06483477
Condition:
Breast Cancer Female
Conditions: Official terms:
Breast Neoplasms
Dermatitis
Conditions: Keywords:
Breast cancer
Radiotherapy
Dermatitis
Mobile application
Study type:
Interventional
Study phase:
N/A
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
multinational, randomized, active-controlled, parallel-group, multicenter trial
Primary purpose:
Prevention
Masking:
None (Open Label)
Intervention:
Intervention type:
Other
Intervention name:
Standard skin care
Description:
From the start of radiotherapy, standard skin care has to be performed by the patient.
This may vary at the participating centers. At the site in Lübeck, it includes fatty
cream with 2-10% urea (fatty cream alone, if patients do not tolerate urea) and, in case
of pruritus, addition of mometasone furoate cream. In case of grade ≥2 moist desquamation
or grade ≥3 radiation dermatitis, each day antiseptic agents will be administered for
wound cleansing followed by administration of silicon or calcium alginate bandage. This
treatment will be continued until moist desquamation radiation disappears and radiation
dermatitis improves to grade 2. Fatty cream with 2-10% urea is applied to the irradiated
skin four times daily. Mometasone furoate cream: In addition to the fatty cream with
2-10% urea, mometasone furoate cream (solution 0.1%) is applied to the irradiated skin
once daily.
Arm group label:
Arm A
Arm group label:
Arm B
Intervention type:
Device
Intervention name:
Reminder App
Description:
In addition to standard skin care, patients are supported by a Reminder App. The purpose
of the app is to remind the patients in an intuitive, unobtrusive and supportive way to
perform skin care. By default, patients are reminded four times a day, but they will also
be able to define a notification schedule that best suits their personal needs. The
patients may postpone each required care procedure for up to 2 hours. With each
procedure, the patients are guided through the skin care with simple and self-explanatory
illustrations. To increase the patients' motivation, they will additionally earn points
for regular and punctual performed care procedures. The patients receive a hand-out
including instructions how to properly perform skin care, but they can also find an
information page within the application that includes similar instructions.
Arm group label:
Arm A
Summary:
In the randomized DAI-BREAC trial, a reminder app will be prospectively tested that
reminds breast cancer patients four times each day to perform the required skin care.
This will likely contribute to the reduction of grade ≥2 radiation dermatitis in these
patients. A total of 268 patients will be randomized to receive standard skin care
supported by a reminder app (Arm A) or standard skin care alone (Arm B). Stratification
will be done using the three factors treatment volume, radiation boost, and at least one
risk factor of dermatitis. Secondary aims include pain (radiation fields), patient
satisfaction with the reminder app (Arm A only), impact of the app on the use of health
technology (Arm A only), and benefit from support by staff members of the treating
Department of Radiation Oncology and/or the UKSH academy regarding the use of the app
(Arm A only).
Detailed description:
The main goal of this trial is to evaluate whether standard skin care supported by a
reminder app is superior to standard skin care alone with respect to prevention of grade
≥2 radiation dermatitis in patients receiving adjuvant radiotherapy for invasive breast
cancer. Radiation dermatitis will be assessed by an observer (specially trained nurse,
technician, or physician) different from the person who performs the routine visit of the
patient ("blinded observer concept"), at the start of radiotherapy and weekly during the
course of radiotherapy, and at the end of the radiotherapy course (=EOT) according to
CTCAE v5.0. Secondary aims include pain (radiation fields), patient satisfaction with the
reminder app (Arm A), impact of the reminder app on the use of health technology (Arm A),
and benefit from support by staff members and/or the UKSH academy regarding the use of
the reminder app (Arm A).
This is a multinational, randomized, active-controlled, open-label, multicenter,
parallel-group trial, which compares the following treatments of radiation related skin
toxicity in patients with breast cancer: Standard skin care supported by a reminder app
(Arm A) vs. standard skin care alone (Arm B). Stratification will be done using the
following prognostic factors:
1. Treatment volume: Breast or chest wall alone vs. breast or chest wall plus lymph
nodes
2. Radiation boost: Yes vs. no
3. At least one risk factor of dermatitis: Yes vs. no Risk factors include chronic
inflammatory disease, significant cardiovascular disease, and smoking history of >10
pack years.
After registration, patients will be randomized in a 1:1 ratio to Arm A or Arm B for
treatment of radiation related skin toxicity. A stratified block-randomization with
random block size will be performed via electronic CRF. The results of the randomization
will be visible only after the input of the stratification factors and only for the
corresponding patient.
This document will be kept at the institution which performs the randomization until the
end of the study. Afterwards, the original randomization list will be kept in the trial
master file at the trial center of the coordinating investigator for a minimum of 10
years after the final report. The randomization will be performed via electronic CRF
centrally by an external company using its standard software. The proceeding for
randomization is based on standard operating procedures (SOPs) of this company. Once the
randomization is allocated to the patient it cannot be changed.
In all patients, radiotherapy will be administered using hypo-fractionation with 40 Gy in
15 fractions of 2.667 Gy given on 5 days per week (overall treatment time = 3 weeks; day
of 15th fraction = EOT), preferably with intensity-modulated radiotherapy (IMRT) or
volumetric-modulated arc therapy (VMAT). Patients aged ≤50 years receive a sequential
radiation boost to the tumor bed of 10 Gy in 5 fractions of 2.0 Gy (on 5 days per week)
following whole-breast irradiation, resulting in an overall treatment time of 4 weeks
(day of 20th fraction = EOT). This accounts also for patients aged ≥51 years with risk
factors for local recurrence. Patients may receive concurrent systemic agents as part of
their standard anticancer treatment, regardless of the participation in this trial. These
agents may include tamoxifen, aromatase inhibitors, or capecitabine [10]. The systemic
agents will be indicated and prescribed by treating medical oncologists or gynecologists
outside this trial. Regarding dose, type and duration of treatment, contraindications,
side effects, pharmacological characteristics and pharmaceutical details of these agents,
please see the corresponding product information.
Standard Skin Care alone (Arm B):
From the start of radiotherapy, standard skin care has to be performed by the patient.
This may vary at the participating centers. At the site in Lübeck, it includes fatty
cream with 2-10% urea (fatty cream alone, if patients do not tolerate urea) and, in case
of pruritus, addition of mometasone furoate cream. In case of grade ≥2 moist desquamation
or grade ≥3 radiation dermatitis, each day antiseptic agents will be administered for
wound cleansing followed by administration of silicon or calcium alginate bandage. This
treatment will be continued until moist desquamation radiation disappears and radiation
dermatitis improves to grade 2. Fatty cream with 2-10% urea is applied to the irradiated
skin four times daily. Mometasone furoate cream: In addition to the fatty cream with
2-10% urea, mometasone furoate cream (solution 0.1%) is applied to the irradiated skin
once daily.
Patients of Arm B will be informed about the importance of skin care prior to the start
of radiotherapy and reminded during their radiotherapy course, when regularly seen by a
radiation oncologist (maximum once a week).
Standard Skin Care plus Reminder App (Arm A):
From the start of radiotherapy, standard skin care has to be performed by the patient as
described for Arm B. In addition, patients of Arm A are supported by a Reminder App,
which is developed by the professional company Nextlabel OHG from Lübeck. The purpose of
the app is to remind the patients in an intuitive, unobtrusive and supportive way to
perform skin care. By default, patients are reminded four times a day, but they will also
be able to define a notification schedule that best suits their personal needs.
Questionnaire regarding the Reminder App and its impact on the use of health technology:
At the end of their radiotherapy course (= EOT), the patients of Arm A will be asked to
complete a questionnaire regarding their satisfaction with the Reminder App. In case of a
dissatisfaction rate >20%, the reminder app is considered to require modifications before
it can be used in future studies. In case of a dissatisfaction rate >40%, it will be
considered not useful. This questionnaire also includes questions regarding the impact of
the app on the use of health technology. Elderly patients aged ≥65 years will be compared
to younger patients aged <65 years to identify potential differences between both age
groups and the need for support regarding the use of the reminder app.
Sample size calculation
The primary goal of this randomized trial is to evaluate whether standard skin care
supported by a reminder app is superior to standard skin care alone with respect to
preventing grade ≥2 radiation dermatitis during adjuvant hypo-fractionated radiotherapy
for breast cancer. According to sample size calculations, 131 patients are required per
study arm within the Full Analysis Set. Considering that 2% of patients will not qualify
for Full Analysis Set, a total of 268 patients should be randomized. The following
analysis sets will be defined for this trial:
Safety Analysis Set: All randomized participants who started radiotherapy. Full Analysis
Set: All randomized patients who have started either therapy with arm A or with arm B and
provide any data on the primary endpoint. The Full Analysis Set will be analyzed
according to the Intention-to-Treat principle, i.e. patients will be analyzed in their
initial group of randomization.
Per Protocol Set: All patients of the Full Analysis Set excluding patients if any of the
following criteria are met:
- Administration of less than 75% of the planned radiation dose if the reason for
discontinuation was any other than death or unacceptable toxicity
- More than 50% missing data on the primary study endpoint All patients in the Per
Protocol Set will be analyzed within their group of actual treatment received.
Statistical analyses:
All data recorded in the electronic case report forms describing the study population and
toxicity will be analyzed descriptively. Categorical data will be presented in
contingency tables with frequencies, percentages and their 95% confidence intervals.
Continuous data will be summarized with at least the following: frequency (n), median,
quartiles, mean, standard deviation (standard error), minimum and maximum. Number of
patients with protocol deviations during the study and listings describing the deviations
will be provided.
In general, chi-square tests will be used to compare percentages in a two-by-two
contingency table, replaced by Fisher´s exact test if the expected frequency in at least
one cell of the associated table is less than 5. Stratified two-by-two contingency tables
will be analyzed using Cochran-Mantel-Haenszel tests. Logistic regression models serve as
multivariable methods for binary endpoint data. Comparison of ordinal variables between
treatment arms will be performed using the asymptotic Wilcoxon-Mann-Whitney test,
replaced by its exact version in case of ordinal categories with small number of
categories and/or sparse data within categories. Any shift in location of quantitative
variables between study groups will be performed with the Wilcoxon-Mann-Whitney tests as
well.
Time-to-event data will be analyzed by Kaplan-Meier methods, when merely non-informative
censoring occurs. For statistical comparison, the log rank-test will be provided
supplemented by multivariate Cox proportional hazards models.
The data analysis will be performed according to the statistical analysis plan (SAP), and
which will be finalized prior to database lock and prior to any statistical analysis.
To evaluate the rate of patients experiencing grade ≥2 radiation dermatitis during their
course of radiotherapy, the worst documented grade during radiotherapy and at EOT is
considered, even if patients have missing visits or discontinue radiotherapy prematurely.
This reflects the "treatment policy estimand" approach.
The rate of patients experiencing grade ≥2 radiation dermatitis will be statistically
compared using the Cochran-Mantel-Haenszel Chi-square test on a two-sided significance
level of 5%. This test is the natural non-parametric extension of the Chi-square test for
testing the treatment effect, while adjusting for the effects of the stratification
variables used for randomization. In case of uneven distribution to stratification
groups, which may result in very small groups the strata might be pooled for analysis.
The decision to pool strata for the analysis will be made before data base lock and
before the final analysis of the data.
For further assessment of the robustness of the results, a logistic regression model for
grade ≥2 radiation dermatitis will be applied including the parameters used for
stratification. A model including additional patient characteristics will be fitted for
exploratory purposes. The confirmatory evaluation will be performed within the Full
Analysis Set; the Per Protocol Set serves for further sensitivity analyses.
The visual analogue scale pain prior to radiotherapy, during radiotherapy and at EOT will
be subjected to descriptive analyses. pain potential differences in pain between
treatment arms, the scores will be subjected to descriptive analysis. For graphical
visualization Box-Whisker diagrams will be provided. Moreover, the change from baseline
values will be considered and subjected to descriptive analyses. Friedman tests and
Wilcoxon-Mann Whitney tests may be applied for comparison of study visits.
At the EOT-visit, patient satisfaction with the reminder app in arm A will be evaluated
and subjected to standard statistical methods. In case of a dissatisfaction rate >20%,
the reminder app needs modifications. In case of a dissatisfaction rate >40%, it will be
considered not useful. In addition, the questions on the impact of the app on the use of
health technology will be evaluated descriptively. Elderly patients aged ≥65 years will
be compared to younger patients aged <65 years to identify potential differences between
both age groups and the need for support regarding the use of the reminder app. Standard
statistical tests serve as a tool for exploratory comparison of age groups.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically proven invasive breast cancer
2. Indication for adjuvant hypo-fractionated radiotherapy
3. Possession of and ability to use a smartphone
4. Female gender
5. Age ≥18 years
6. Written informed consent
7. Capacity of the patient to contract
Exclusion Criteria:
1. Pregnancy, Lactation
2. Expected non-compliance
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Vejle Hospital, University Hospital of Southern Denmark
Address:
City:
Vejle
Zip:
7100
Country:
Denmark
Contact:
Last name:
Charlotte Kristiansen, MD
Phone:
0045-7940
Phone ext:
6094
Email:
charlotte.kristiansen@rsyd.dk
Facility:
Name:
Medical Practice for Radiotherapy and Radiation Oncology
Address:
City:
Hannover
Zip:
30161
Country:
Germany
Contact:
Last name:
Stefan Janssen, MD
Phone:
0049-511-220
Phone ext:
60420
Email:
stefan.janssen@uksh.de
Facility:
Name:
Medical School Hamburg, Schwerin Campus
Address:
City:
Schwerin
Zip:
19055
Country:
Germany
Contact:
Last name:
Marciana N Duma, MD
Phone:
0049-385-520
Phone ext:
5070
Email:
Marciana.Duma@helios-gesundheit.de
Facility:
Name:
Malteser Hospital St. Franziskus
Address:
City:
Flensburg
Zip:
24939
Country:
Germany
Contact:
Last name:
Carmen Timke, MD
Phone:
0049-461-816
Phone ext:
2518
Email:
carmen.timke@malteser.org
Facility:
Name:
Department of Radiation Oncology, University of Lübeck and University Medical Center Schleswig-Holstein
Address:
City:
Lubeck
Zip:
23562
Country:
Germany
Contact:
Last name:
Dirk Rades, Prof. Dr.
Phone:
+49-451-500
Phone ext:
45400
Email:
dirk.rades@uksh.de
Contact backup:
Last name:
Carlos Andres Narvaez
Phone:
+49-451-500
Phone ext:
45420
Email:
carlosandres.narvaez@uksh.de
Contact backup:
Last name:
Dirk Rades, Prof. Dr.
Contact backup:
Last name:
Liesa Dziggel, Dr.
Contact backup:
Last name:
Calos A Narvaez-Wolf, Dr.
Contact backup:
Last name:
Maike Radtke, Dr.
Contact backup:
Last name:
Christian Staackmann, Dr.
Start date:
November 15, 2024
Completion date:
September 30, 2026
Lead sponsor:
Agency:
University Hospital Schleswig-Holstein
Agency class:
Other
Collaborator:
Agency:
University of Southern Denmark
Agency class:
Other
Collaborator:
Agency:
Medical School Hamburg
Agency class:
Other
Source:
University Hospital Schleswig-Holstein
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06483477
