## Protocol Section
### Identification Module
**NCT ID:** NCT01688479

**Brief Title:** Trial Comparing Calendula Officinalis With Aqueous Cream "Essex" to Treat Skin Reactions From Radiotherapy of Breast Cancer

**Official Title:** Randomized, Blinded Phase III Trial Comparing Calendula Officinalis Cream With Standard Aqueous Cream "Essex" for Treatment of Skin Reactions Caused by Postoperative Radiotherapy of Breast Cancer

#### Organization Study ID Info
**ID:** Calendula trial
#### Organization
**Class:** OTHER
**Full Name:** Karolinska University Hospital
### Status Module
#### Completion Date
**Date:** 2012-09

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2015-09-17

**Type:** ESTIMATED

**Last Update Submit Date:** 2015-09-16

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2012-03

**Type:** ACTUAL

#### Start Date
**Date:** 2011-02

**Status Verified Date:** 2015-09

#### Study First Post Date
**Date:** 2012-09-20
**Type:** ESTIMATED
**Study First Submit Date:** 2012-09-15
**Study First Submit QC Date:** 2012-09-19
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Karolinska University Hospital

#### Responsible Party

**Investigator Affiliation:** Karolinska University Hospital

**Investigator Full Name:** Thomas Hatschek

**Investigator Title:** MD, PhD, Assoc. prof.

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** Acute radiation skin reactions (ARSR) occur in the majority of patients undergoing postoperative radiotherapy (RT). Some patients experience more severe reactions such as dry and/or moist desquamation but most patients experience mild reactions e.g. erythema (Lopez et al., 2005). The radiation dose, volume, RT technique and previous treatment, such as type of surgery and previous chemotherapy, are factors that might impact on the risk for ARSR together with patient-related factors such as body mass index (BMI), smoking status and previous skin damage (Porock et al., 1998; Wells et al., 2004). In a pilot study (n=93) of the frequency of ARSR in patients with breast cancer who underwent adjuvant RT it was shown that 93% developed ARSR, mostly mild reactions. Patients reported low scores on pain and itching (Sharp et al., 2011). Over 80% of the patients reported adherence to the skin care recommendations which included application of a thin layer of Essex® cream, a non-perfumed aqueous cream, on the irradiated area at least two times a day (Sharp et al., 2011). The effects of skin care products containing Calendula Officinalis (marigold plant) on ARSR in patients with breast cancer were investigated in a randomized clinical trial (Pommier et al., 2004). Patients in the experimental group, treated with calendula cream had a statistically significant lower incidence of severe ARSR, pain and treatment interruptions in comparison with the patients in the control group, treated with trolamine.

The purpose of this blinded, randomized clinical trial is to compare two topical agents, Calendula Weleda® cream and Essex® cream, in terms of efficacy to reduce the risk of severe acute radiation skin reactions (ARSR) in relation to adjuvant radiotherapy (RT) for breast cancer.

Patients were instructed to apply a thin layer of the assigned cream twice a day, starting at the onset of RT and continue until two weeks after termination, or until the ARSR is healed. The application should include the whole treatment area including the armpit and shoulder/back area in patients treated with modified radical mastectomy. Patients are also advised to not apply the cream within two hours before the RT in order to avoid possible build-up effect. Daily wash with perfume free soap and tap water are recommended and patients are advised to refrain from use of other topical agents in the irradiated area.

The primary endpoint is the efficacy to reduce acute radiation skin reactions (ARSR), assessed with the Radiation Therapy Oncology Group/The Organization for Research and Treatment of Cancer Acute Radiation Morbidity Scoring Criteria (RTOG/EORTC scale) at follow-up.

Secondary endpoints include patient reported outcome measures; Quality of Life Questionnaire (QLQ-C30), Sleep disturbances (MOS-sleep questionnaire) and symptoms experienced from the irradiated area (visual analogue scale). Patients' experiences and adherence to the topical agents are also evaluated.

A total of 400 patients are required to detect a true absolute reduction in the proportion of patients with ARSR, from 35% with standard treatment (Essex® cream) to 20% with the experimental treatment (Calendula Weleda® cream), with a significance level of 5% a power of 90%. With this sample size, 95% confidence intervals for the difference in proportions are estimated to be in the order of ±10%. Assuming a rate of 5% of non-responders, the target size has been set to 420 patients.

### Conditions Module

**Conditions:**

- Postoperative Radiotherapy Breast Cancer

**Keywords:**

- Postoperative radiotherapy

- breast cancer

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** QUADRUPLE

**Who Masked:**

- PARTICIPANT

- CARE_PROVIDER

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 420

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Calendula Officinalis (marigold plant) is applied twice daily on the skin in the radiated area during the entire treatment period and until the skin reaction subsided

**Intervention Names:**

- Drug: Calendula Weleda cream (Weleda AG, Sweden) contains extracts of marigold plant (Calendula Officinalis 10%), wool fat and sesame oil

**Label:** Calendula Weleda® cream (Weleda)

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Essex cream is applied twice daily on the skin in the radiated area during the entire treatment period and until the skin reaction subsided

**Intervention Names:**

- Drug: Essex® cream (Schering-Plough), aqueous cream without parabens

**Label:** Essex® cream (Schering-Plough)

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Calendula Weleda® cream (Weleda)

**Name:** Calendula Weleda cream (Weleda AG, Sweden) contains extracts of marigold plant (Calendula Officinalis 10%), wool fat and sesame oil

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Essex® cream (Schering-Plough)

**Name:** Essex® cream (Schering-Plough), aqueous cream without parabens

**Type:** DRUG

### Outcomes Module

#### Other Outcomes

**Description:** Collection of data on smoking habits and measurements of carbon monoxide in exhaled air

**Measure:** Impact of smoking habits on the intensity of the skin reaction

**Time Frame:** 8 weeks

#### Primary Outcomes

**Description:** Skin reactions due to radiotherapy using RTOG scale

**Measure:** Grade of skin reactions to radiotherapy

**Time Frame:** 8 weeks

#### Secondary Outcomes

**Description:** Measurements of sleep disturbances acc. to the MOS-SLEEP scale and QoL acc. to EORTC QLQ-C30

**Measure:** Quality of life in relation to skin reaction

**Time Frame:** 8 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* radically operated for breast cancer,
* aged 18 years or older,
* signed informed consent

Exclusion Criteria:

* previous radiation in the same area,
* severe general health problems,
* ECOG performance status \> 3,
* reduced cognitive ability,
* allergy to marigold plant

**Minimum Age:** 18 Years

**Sex:** FEMALE

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Stockholm

**Country:** Sweden

**Facility:** Department of Oncology, Karolinska University Hospital

**Zip:** 17176

#### Overall Officials

**Official 1:**

**Affiliation:** Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden

**Name:** Maria AC Bergenmar, PhD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 2:**

**Affiliation:** Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden

**Name:** Lena Sharp, PhD

**Role:** PRINCIPAL_INVESTIGATOR

**Official 3:**

**Affiliation:** Dept of Oncology, Karolinska University Hospital, Stockholm, Sweden

**Name:** Thomas Hatschek, MD, PhD

**Role:** STUDY_CHAIR

### References Module

#### References

**Citation:** Sharp L, Finnila K, Johansson H, Abrahamsson M, Hatschek T, Bergenmar M. No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions--results from a randomised blinded trial. Eur J Oncol Nurs. 2013 Aug;17(4):429-35. doi: 10.1016/j.ejon.2012.11.003. Epub 2012 Dec 13.

**PMID:** 23245940

**Citation:** Sharp L, Johansson H, Hatschek T, Bergenmar M. Smoking as an independent risk factor for severe skin reactions due to adjuvant radiotherapy for breast cancer. Breast. 2013 Oct;22(5):634-8. doi: 10.1016/j.breast.2013.07.047. Epub 2013 Aug 13.

**PMID:** 23953136

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000009369

- Term: Neoplasms

- ID: D000001941

- Term: Breast Diseases

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M5220

- Name: Breast Neoplasms

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M5218

- Name: Breast Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001943

- Term: Breast Neoplasms

### Intervention Browse Module - Browse Branches

- Abbrev: HB

- Name: Herbal and Botanical

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: T89

- Name: Calendula

- Relevance: HIGH

- As Found: Disposable needles

### Misc Info Module

- Version Holder: 2024-05-24
