Ignite Creation Date:
2024-07-17 @ 11:46 AM
Last Modification Date:
2024-10-26 @ 3:33 PM
Study NCT ID:
NCT06483477
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-07-03
First Post:
2024-06-21
Brief Title:
Dermatitis During Adjuvant Irradiation for BREAst Cancer
Sponsor:
University Hospital Schleswig-Holstein
Organization:
University Hospital Schleswig-Holstein
Study Overview
Official Title:
Dermatitis During Adjuvant Irradiation for BREAst Cancer Grade 2 Radiation Dermatitis in Breast Cancer Patients with or Without a Mobile Application Reminder-App
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DAI-BREAC
Brief 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 andor 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 v50 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 andor 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 11 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 2667 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 20 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 01 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 ie 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 Fishers 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 andor 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
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 11 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 2667 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 20 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 01 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 ie 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 Fishers 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 andor 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None