Condition category
Skin and Connective Tissue Diseases
Date applied
09/11/2018
Date assigned
03/12/2018
Last edited
03/12/2018
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Not yet recruiting

Plain English Summary

Background and study aims
Breast irradiation (radiotherapy) after breast surgery is a standard of care for about half of the patients with breast cancer. Localized radiotherapy is delivered daily during a few weeks to the breast area. During this period, the irradiated skin can be damaged. Mild redness is the first sign to appear generally within few hours of radiation exposure, even if the most common skin reactions occur about 10–14 days after the beginning of the therapy and may include symptoms like skin swelling, dryness, burning, itching, tenderness, change in skin colour and skin lesions. Such symptoms disappear after the radiation therapy has finished. However, sometimes skin reactions are so intense that the patient is obliged to discontinue radiotherapy. The application during radiotherapy of hydrating creams on the irradiated skin area can help reducing the risk of severe skin damage. The product used in this study is a cream containing hylauronic acid, a natural component of the skin with hydrating and cicatrizing properties. This product is already used for the treatment of skin wounds, including chronic wounds like leg ulcers. The aim of this study is to find out whether twice daily application (morning and evening) of the cream with hyaluronic acid before, during and after radiotherapy, is able to reduce the severity of skin damage.

Who can participate?
Women aged 18 and over who have undergone surgery for breast cancer and are scheduled for radiotherapy

What does the study involve?
Participants are randomly allocated to receive either the test cream or a neutral cream (the same cream without hyaluronic acid). The occurrence and the intensity of skin reactions are assessed both by the responsible physician and by means of an instrument (spectrophotometer) that can measure exactly the intensity of the colour of the irradiated skin and depict any change occurred during the study as a consequence of the radiotherapy. Moreover, any other discomfort caused by the radiotherapy and its impact on daily life or any side effects of the applied cream are reported during the study period. Participants attend a maximum of 9 visits at the clinical site where the radiotherapy is delivered. Also, participants have to avoid the application on the irradiated skin area of any other product (including cosmetic products) and have to avoid exposure of the area to sun/sunbed during the whole study period. The patients under chemotherapy or who are under treatment with corticosteroids or other drugs known to or suspected of compromising the immune system (immunosuppressive therapy) are not allowed to participate. Patient who are allergic to the test cream or to one of its components should not participate in the study. If an allergic reaction develops during the study, the treatment with the cream has to be stopped. However, the radiotherapy can be continued, based on the opinion of the responsible physician.

What are the possible benefits and risks of participating?
The prevention or reduction in intensity of the skin reaction generally experienced during and after radiotherapy are potential benefits for study participants. Possible risks include the occurrence of eczema, allergy, and hypersensitivity reactions to the tested creams. Severe reactions to the test cream have been very rarely reported.

Where is the study run from?
Istituto Oncologico della Svizzera Italiana (IOSI) in Bellinzona (Ticino, Switzerland)

When is the study starting and how long is it expected to run for?
May 2018 to June 2020

Who is funding the study?
IBSA Institut Biochimique S.A (Switzerland)

Who is the main contact?
Dr Antonella Richetti

Trial website

Contact information

Type

Scientific

Primary contact

Dr Antonella Richetti

ORCID ID

Contact details

Via Ospedale
Bellinzona
6500
Switzerland

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

18CH-Iccr05

Study information

Scientific title

Mono-centre, prospective, placebo-controlled, double-blind, in parallel groups randomized clinical trial to evaluate the effectiveness of hyaluronic acid 0.2% cream for the prevention of skin toxicity in breast cancer patients treated with post-operative radiotherapy

Acronym

Study hypothesis

To demonstrate the superiority of HA 0.2% cream in reducing the incidence of Grade ≥ 2 radiodermatitis, as compared to a neutral comparator (placebo) cream, when daily applied starting 2 weeks before local radiotherapy (LRT), during the LRT period until 2 weeks after the end of LRT.

Ethics approval

Comitato Etico del Cantone Ticino, Bellinzona, Ticino-Switzerland, 22/10/2018

Study design

Monocentric prospective double-blind (Investigator- and patient-blinded) controlled clinical trial

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Radiodermatitis

Intervention

The tested Investigational Product HA 0.2% cream, or Ialuset® cream, is a CE-marked medical device, classified as Class IIb, available as 100 g tubes. The neutral comparator (placebo) cream is physically and visually indistinguishable from the test.

Adult female subjects having undergone curative surgery for unilateral stage I-III breast cancer and being scheduled for adjuvant LRT with conventional fractionation or hypofractionation at the investigation site, will be enrolled in the trial after having given written informed consent. According to a pre-established randomization sequence, the subjects will be treated daily with either HA 0.2% cream or neutral comparator cream, for 2 weeks before starting LRT up to 2 weeks after the end of a 6-week LRT (10 weeks of cream treatment) or 3-week LRT if hypofractionated schedule [15 fractions] (7 weeks of cream treatment in total). Patients will apply the cream twice daily, every 12 hours, with a dose sufficient to uniformly cover with a thin layer the whole cutaneous irradiated area (breast or chest wall). A wash out period of at least 6 hours has to be observed between the cream application and the irradiation. During the study participants attend a maximum of 9 control visits, always at the clinical site where the radiotherapy is delivered, to follow up treatment performance and tolerability.

Intervention type

Device

Phase

Drug names

Primary outcome measure

Proportion (%) of patients developing skin reactions (radiodermatitis) of Grade ≥ 2, as assessed by the Investigator according to the RTOG score, at the end of the LRT period

Secondary outcome measures

1. Proportion (%) of patients developing skin reactions (radiodermatitis) of Grade ≥ 2, as assessed by the Investigator according to the RTOG score, during the LRT period and in the 2-week follow-up
2. Skin reaction (erythema/inflammation) severity, as assessed by skin reflectance spectrophotometry (SRS) at the Screening/Enrolment visit (baseline assessment), after irradiation on Day 1 (LRT start), and on each of the subsequent weekly Control Visits during LRT, as well as at the end of the 2-week follow-up period (End-of-Study visit)
3. Time (days) to reach a Grade ≥ 2 skin reaction (radiodermatitis), as assessed by the Investigator according to the RTOG score at each post-baseline control visit
4. Total delivered dose (Gy) to reach a Grade ≥ 2 skin reaction (radiodermatitis), as assessed by the Investigator according to the RTOG score at each post-baseline control visit
5. Proportion (%) of patients developing a Grade ≥ 3 skin toxicity at the irradiated site, as assessed by the Investigator according to the RTOG score, at each control visit
6. Patient's self-perceived Level of Discomfort at the irradiated site as assessed on a 0-100 mm Visual Analog Scale (VAS), anchored to 0 = no discomfort at all and 100 = worst possible discomfort, at each control visit
7. Patient’s Quality of Life (QoL), as assessed by the patient using a self-administered QoL questionnaire (Short Form 36 – SF36) at screening/enrolment visit, start of LRT visit and at the follow-up visit
8. The Overall Treatment Performance, judged by the Investigator using a 5-point scale (4 = Excellent; 3 = Good; 2 = Fair; 1 = Poor; 0 = None) at the end of the study
9. The safety of use of study medication evaluated by means of AEs and Treatment Emergent AEs (TEAEs) (Common Terminology Criteria for Adverse Events v4.03) (incidence, severity, duration, and causal relationship with the IP will be assessed), occurring at any time during the study
10. Overall Treatment Tolerability, independently judged by the Investigator and Patient using a 5-point scale (4 = excellent; 3 = good; 2 = fair; 1 = poor; 0 = none) at the end of the study

Overall trial start date

09/05/2018

Overall trial end date

30/06/2020

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Females aged ≥18 years
2. Having undergone curative surgery for unilateral stage I-III breast cancer and scheduled for adjuvant LRT with conventional fractionation or hypofractionation according to the site guidelines; performance status ECOG 0-1
having given written informed consent to participate in the study according to Good Clinical Practice (GCP)
3. Able to comprehend the full nature and the purpose of the study, including possible risks and side effects, and able to cooperate with the Investigator and to comply with the requirements of the entire study (including ability to attend all the planned study visits according to the time limits), based on Investigator’s judgement
4. Females of childbearing potential (i.e., not permanently sterilised - post hysterectomy or tubal ligation status – or not postmenopausal) must use an appropriate method of contraception for at least 30 days before inclusion in the study and during the whole study period; for all females of childbearing potential (i.e., not permanently sterilised - post hysterectomy or tubal ligation status – or not postmenopausal) the pregnancy test result must be negative at Screening/Enrolment visit of the study

Participant type

Patient

Age group

Adult

Gender

Female

Target number of participants

120 participants (60 in each treatment group)

Participant exclusion criteria

1. Presence of any dermatologic disease or condition or conditions known to alter skin appearance or physiologic response that might interfere with evaluation of the test site reaction or contraindicate participation
2. Ipsilateral relapsing/second breast tumour or previous LRT on the same volumes
3. Concomitant chemotherapy
4. Patients treated with mastectomy and autologous reconstruction
5. Positioning of “bolus” on chest wall
6. Allergy to the components contained in the IP; history of anaphylaxis or allergic reactions to any other allergens potentially affecting the study outcome
7. Underlying disease (T-lymphocytes impairment) or concomitant treatment with systemic (oral, parenteral) corticosteroids, as well as with any other drugs known to or suspected of compromising the subject's immune system (immunosuppressive therapy)
8. Clinically significant or unstable concurrent disease whose sequelae or treatment might interfere with the study evaluation parameters
9. Major psychiatric disorders that, in the view of the Investigator, could compromise the patient’s participation in the study
10. Positive or missing pregnancy test at Screening/Enrolment visit, or breastfeeding women
11. Concomitant participation in other clinical trials or participation in the evaluation of any IMDs/IMPs during 3 months before this study or previous participation in the same study
12. Participation in the study is also not permitted to employees of the Investigator or study centre with direct involvement in the trial or in other trials under the direction of that Investigator, as well as family members of the employees or the Investigator

Recruitment start date

02/01/2019

Recruitment end date

31/03/2020

Locations

Countries of recruitment

Switzerland

Trial participating centre

Istituto Oncologico della Svizzera Italiana (IOSI)
Ente Ospedaliero Cantonale (EOC) Via Ospedale
Bellinzona
6500
Switzerland

Sponsor information

Organisation

IBSA, Institut Biochimique S.A

Sponsor details

Via del Piano
29
Pambio-Noranco
6915
Switzerland

Sponsor type

Industry

Website

www.ibsa.ch

Funders

Funder type

Industry

Funder name

IBSA, Institut Biochimique S.A

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The results will be published in one or more separate articles following completion of the clinical investigation.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

31/12/2020

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes