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

Evaluation of the Clinical Benefit of a Spa Care on the Evolution of Late Fibrosis After Postoperative Radiotherapy for Breast Cancer in Remission

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.

Study Overview

• Status: Unknown
• Conditions: Fibrosis; Breast Carcinoma
• Intervention / Treatment: Other: skin-oriented spa care; Drug: Pentoxifylline; Drug: Tocopherol acetate

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 Type: Interventional
• Enrollment (Anticipated): 142
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Besançon, France, 25000
    • CHU de Besancon Hopital Jean Minjoz
  • Béziers, France, 34500
    • ONCODOC
  • Chalon-sur-Saône, France, 71100
    • Centre d'Oncologie et de Radiothérapie du Parc
  • Charleville-Mézières, France, 08000
    • Clinique du Parc de Charleville-Mézières
  • Clermont Ferrand, France, 63000
    • CLCC Jean Perrin
  • Colmar, France, 68000
    • Hôpitaux Civils de Colmar
  • Dijon, France, 21079
    • Centre Georges-Francois Leclerc
  • Grenoble, France, 38000
    • Institut Daniel Hollard
  • La Tronche, France, 38700
    • CHU de Grenoble, Hôpital A.Michallon
  • Metz, France
    • CHR Metz-Thionville Hopital de Mercy
  • Montbéliard, France, 25200
    • CH de Belfort-Montbéliard Site du Mittan
  • Mulhouse, France, 68100
    • CH de Mulhouse
  • Nancy, France, 54100
    • Centre d'oncologie de Gentilly
  • Poitiers, France, 86000
    • CHU de Poitiers
  • Reims, France, 51100
    • Institut Jean Godinot de Reims
  • Saint-Priest en Jarez, France, 42270
    • CLCC Saint Etienne
  • Strasbourg, France, 67000
    • Centre Paul Strauss
  • Strasbourg, France, 67000
    • Clinique de l'Orangerie
  • Toulouse, France, 31000
    • Institut universitaire du cancer
  • Troyes, France, 10000
    • CH de Troyes
  • Vandoeuvre-les-Nancy, France, 54519
    • Institut de Cancérologie de Lorraine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: combination tocopherol/pentoxifylline + spa care; pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months AND skin-oriented spa care (18 days)	Other: skin-oriented spa care; standardized procedure : 72 care sessions over 18 days of treatment +/- Additional care according to the specificity of each spa; Drug: Pentoxifylline; 400 mg bid during at least 6 months; Drug: Tocopherol acetate; 500 mg bid during at least 6 months
ACTIVE_COMPARATOR: combination tocopherol/pentoxifylline; pentoxifylline (400 mg bid) + tocopherol (500 mg x bid) during at least 6 months	Drug: Pentoxifylline; 400 mg bid during at least 6 months; Drug: Tocopherol acetate; 500 mg bid during at least 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dermatology Quality of life at 6 months	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.	6 months after the end of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dermatology Quality of life at 12 months	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.	12 months after the end of treatment
Overall quality of life	quality of life questionnaire (EORTC QLQ C30 score)	6 months
Breast-oriented quality of life	EORTC QLQ-BR23 score	6 months
late radiation toxicity	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	6 months
Skin thickness	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	6 months
Cosmetic appearance	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	6 months

Collaborators and Investigators

• Sponsor: Institut de Cancérologie de Lorraine
• Collaborators: Association Francaise pour la Recherche Thermale

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 1, 2018
• Primary Completion (ANTICIPATED): July 1, 2020
• Study Completion (ANTICIPATED): December 1, 2021

Study Registration Dates

• First Submitted: September 8, 2016
• First Submitted That Met QC Criteria: September 8, 2016
• First Posted (ESTIMATE): September 13, 2016

Study Record Updates

• Last Update Posted (ACTUAL): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: radiotherapy; randomised controlled trial; spa care; pentoxifylline/tocopherol combination; late sequelae
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Fibrosis; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Micronutrients; Vitamins; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Vitamin E; Tocopherols; alpha-Tocopherol; Tocotrienols; Pentoxifylline
• Other Study ID Numbers: 2016-003518-28

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No