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

Sponsor

Institut de Cancérologie de Lorraine (Other)

Overall Status

Unknown status

CT.gov ID

NCT02898376

Collaborator

Association Francaise pour la Recherche Thermale (Other)

142

Enrollment

Locations

Arms

Anticipated Duration (Months)

6.8

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Carcinoma Fibrosis	Other: skin-oriented spa care Drug: Pentoxifylline Drug: Tocopherol acetate	Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

142 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

Official Title:

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

Anticipated Study Start Date :

Dec 1, 2018

Anticipated Primary Completion Date :

Jul 1, 2020

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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)
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
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 80 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	CHU de Besançon Hôpital Jean Minjoz	Besançon	France	25000
2	ONCODOC	Béziers	France	34500
3	Centre d'Oncologie et de Radiothérapie du Parc	Chalon-sur-Saône	France	71100
4	Clinique du Parc de Charleville-Mézières	Charleville-Mézières	France	08000
5	CLCC Jean Perrin	Clermont Ferrand	France	63000
6	Hôpitaux Civils de Colmar	Colmar	France	68000
7	Centre Georges-François Leclerc	Dijon	France	21079
8	Institut Daniel Hollard	Grenoble	France	38000
9	CHU de Grenoble, Hôpital A.Michallon	La Tronche	France	38700
10	CHR Metz-Thionville Hôpital de Mercy	Metz	France
11	CH de Belfort-Montbéliard Site du Mittan	Montbéliard	France	25200
12	CH de Mulhouse	Mulhouse	France	68100
13	Centre d'Oncologie de Gentilly	Nancy	France	54100
14	CHU de Poitiers	Poitiers	France	86000
15	Institut Jean Godinot de Reims	Reims	France	51100
16	CLCC Saint Etienne	Saint-Priest en Jarez	France	42270
17	Centre Paul Strauss	Strasbourg	France	67000
18	Clinique de l'Orangerie	Strasbourg	France	67000
19	Institut Universitaire du Cancer	Toulouse	France	31000
20	CH de Troyes	Troyes	France	10000
21	Institut de Cancérologie de Lorraine	Vandoeuvre-les-Nancy	France	54519