Clinical Benefit of Spa Care on Severe Radiation-induced Fibrosis After Postoperative Radiotherapy for Breast Cancer

Phase 3

• Conditions: Fibrosis; Breast Carcinoma
• Interventions: Other: skin-oriented spa care; Drug: Pentoxifylline; Drug: Tocopherol acetate

• Registration Number: NCT02898376
• Lead Sponsor: Institut de Cancérologie de Lorraine

Brief Summary

This study evaluates the dermatological life quality six months after spa cares in patients with severe late toxicity involving the skin and / or soft tissues after postoperative radiotherapy for breast cancer. Half of the patients will be treated with a combination of pentoxifylline (PTX) and alpha-tocopherol (Vit E) when Half of the patients will receive skin-oriented spa cares in addition.

Detailed Description

The combination of PTX and vit E appears as the standard treatment of radiation induced fibrosis. Synergism between PTX and Vit E is likely, as treatment with each drug alone is ineffective. This combination was also positively evaluated in the treatment of osteoradionecrosis, radiation-induced pelvic neuropathies, pneumoniae as well as bowel pathologies.

Spa cares are part of the standard treatment of burn scars. Two spa treatments per year enable the mitigation or disappearance (after several treatments) of pruritus, dysesthesia, local inflammation, hypertrophy and sclerosis. They promote the healing of chronic superficial erosions. The spa treatment combines baths, sprays and especially filiform showers with thermal water jets under high pressure for a few minutes.

Study Timeline

• Study First Submitted: 2016-09-08
• Study First Submitted QC: 2016-09-08
• Study First Posted: 2016-09-13
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-07
• Last Update Posted: 2018-08-08
• Study Start: 2018-12
• Primary Completion: 2020-07
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 142

Inclusion Criteria

• women
• age ≥ 18 and <80 years old
• invasive or in situ breast carcinoma
• non-metastatic disease.
• postoperative radiotherapy completed since at least 6 months
• unilateral breast radiotherapy
• grade > 2 dermal and/or soft tissue toxicity (CTCAE v4.0)
• no inflammatory ou infectious flare on the breast at the time of inclusion
• ability to provide an informed written consent form
• affiliation to a social security system

Exclusion Criteria

• age <18 or ≥ 80 years old

• evolutive cancer

• Metastatic Disease

• Patient undergoing specific treatment for breast cancer (except adjuvant endocrine therapy and / or adjuvant Herceptin) at the time of inclusion

• bilateral Breast/chest wall Radiotherapy

• breast prosthesis bearer

• Body Mass Index > 40 or <18.5

• chronic skin ulceration within the treated breast at the time of inclusion

• contraindications to spa care :

  • inflammatory disease in flare at the time of inclusion
  • active infections
  • heart failure (NYHA class> 1)
  • chronic respiratory failure
  • labile blood pressure
  • bullous dermatitis

• evolutive chronic skin disease

• hypersensitivity to pentoxifylline or any of the excipients

• acute myocardial infarction

• ongoing hemorrhage or major bleeding risk

• use of oral anticoagulants

• pregnant or likely to be in 6 months or breastfeeding

• patients deprived of liberty or under supervision

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
combination tocopherol/pentoxifylline + spa care	skin-oriented spa care	pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months AND skin-oriented spa care (18 days)
combination tocopherol/pentoxifylline + spa care	Pentoxifylline	pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months AND skin-oriented spa care (18 days)
combination tocopherol/pentoxifylline	Tocopherol acetate	pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months
combination tocopherol/pentoxifylline + spa care	Tocopherol acetate	pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months AND skin-oriented spa care (18 days)
combination tocopherol/pentoxifylline	Pentoxifylline	pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months

Primary Outcome Measures

Name	Time	Method
Dermatology Quality of life at 6 months	6 months after the end of treatment	Self-reported dermatology quality of life using the standardized Dermatology Life Quality Index (DLQI) ; This score assess the functional impact of fibrosis: eg. intensity of pain, itching... (10 items). The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.

Secondary Outcome Measures

Name	Time	Method
Breast-oriented quality of life	6 months	EORTC QLQ-BR23 score
late radiation toxicity	6 months	Evaluation of late toxicity performed independently and in blind by another radiation oncologist from the same center, using the CTCAE v4.0 scale modules: Skin and subcutaneous tissue disorders / Musculoskeletal skeletal / Reproductive organs and breast
Skin thickness	6 months	The skin thickness will be assessed in blind by an independently radiologist using a standardized Ultrasound scan procedure (Yoshida EJ, et al; Int J Radiat Oncol Biol Phys. 2012) Skin thickness is measured as the distance between the entry ultrasound echo signal to the border between the dermis and hypodermis . Measurements are acquired from ten locations: five on the treated (irradiated) breast (12:00, 3:00, 6:00, 9:00, and tumor bed), and five corresponding locations on the untreated (contralateral) breast - serving as controls to account for patient baseline variation
Dermatology Quality of life at 12 months	12 months after the end of treatment	Self-reported dermatology quality of life using the standardized Dermatology Life Quality Index (DLQI) ; This score assess the functional impact of fibrosis: eg. intensity of pain, itching... (10 items). The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and a minimum of 0. The higher the score, the more quality of life is impaired.
Overall quality of life	6 months	quality of life questionnaire (EORTC QLQ C30 score)
Cosmetic appearance	6 months	The cosmetic appearance will be evaluated by the investigator with the Harvard-breast-cosmesis-scale (HBCS). HBCS classifies the overall aesthetic results in four categories from excellent, good, fair to poor; comparing the treated breast to the control breast

Trial Locations

Locations (21)

Hôpitaux Civils de Colmar; 🇫🇷 Colmar, France

Institut Daniel Hollard; 🇫🇷 Grenoble, France

CLCC Saint Etienne; 🇫🇷 Saint-Priest en Jarez, France

Centre Paul Strauss; 🇫🇷 Strasbourg, France

CH de Troyes; 🇫🇷 Troyes, France

ONCODOC; 🇫🇷 Béziers, France

Centre d'Oncologie et de Radiothérapie du Parc; 🇫🇷 Chalon-sur-Saône, France

CHU de Grenoble, Hôpital A.Michallon; 🇫🇷 La Tronche, France

CHU de Poitiers; 🇫🇷 Poitiers, France

CHU de Besançon Hôpital Jean Minjoz; 🇫🇷 Besançon, France

Clinique du Parc de Charleville-Mézières; 🇫🇷 Charleville-Mézières, France

CLCC Jean Perrin; 🇫🇷 Clermont Ferrand, France

Centre Georges-François Leclerc; 🇫🇷 Dijon, France

CHR Metz-Thionville Hôpital de Mercy; 🇫🇷 Metz, France

Centre d'Oncologie de Gentilly; 🇫🇷 Nancy, France

Institut Jean Godinot de Reims; 🇫🇷 Reims, France

CH de Belfort-Montbéliard Site du Mittan; 🇫🇷 Montbéliard, France

Clinique de l'Orangerie; 🇫🇷 Strasbourg, France

CH de Mulhouse; 🇫🇷 Mulhouse, France

Institut Universitaire du Cancer; 🇫🇷 Toulouse, France

Institut de Cancérologie de Lorraine; 🇫🇷 Vandoeuvre-les-Nancy, France