Curative Efficacy of Pravastatine in Patients Presented Delayed Cutaneous and Subcutaneous Radio-induced Fibrosis

Study Overview
=================
Brief Summary
-----------------
Molecular mechanisms involved in radio-induced fibrosis are assessed in UPRES EA 27-10 since 10 years. Besides the canonical TGFbeta/ Smad pathway involved in radio-induced fibrosis (RIF), the Rho/ROCK/CTGF cascade has been shown to be also implicated in molecular mechanisms of RIF. Curative administration of Pravastatin or ROCK specific inhibitors inhibits the chronically activated Rho/ROCK/CTGF pathway in vitro in human cells lines and ex vivo in human samples. In addition, the curative administration of Pravastatin improves established RIF in vivo. The investigators data suggest that the pravastatin-based strategy is an efficient and safe antifibrotic therapy, easily transferable into the clinic to improve the quality of life of long-term cancer survivors without interfering with prior anticancer treatment. This clinical trial evaluates the curative efficacy of Pravastatine in patients who presented a cutaneous and/ or subcutaneous fibrosis (grade >= 2 according to NCI-CTCAE v4 toxicities scale) and who were treated by radiotherapy for a head and neck cancer. Patients will be treated by Pravastatin during 12 months. An intermediate evaluation of efficacy by ultrasound will be assessed at 6 months and at last, at the end of the treatment. Patients assessment will be performed at 6 and 12 months after the end of the treatment to look at a potential rebound effect. Objective(s) of the clinical study Main objective: To assess Pravastatin efficacy in established cutaneous and subcutaneous radio-induced fibrosis revealed from 6 to 24 months after head and neck radiotherapy. Second objective: To evaluate radio-induced fibrosis regression during the year following treatment stop.

Official Title
-----------------
Curative Efficacy of Pravastatine in Patients Presented Delayed Cutaneous and Subcutaneous Radio-induced Fibrosis

Conditions
-----------------
Fibrosis

Intervention / Treatment
-----------------
* Drug: Pravastatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Grade >= 2 cutaneous and/or subcutaneous fibrosis (NCI-CTCAE v4 toxicities scale) revealed from 6 to 24 months after head and neck radiotherapy. Head and neck cancers treated by radiation therapy +/- chemotherapy, +/- surgery, with no evidence of progressive disease. Age >= 18 Karnofsky PS ≥ 70 normal renal function (plasmatic creatinine <= 130 micromol/l), normal cholesterol, normal hepatic function (total bilirubin <= 1.5 UNL, SGOT and SGPT <= 2 UNL) Written informed consent of the patient. Exclusion Criteria: any chronic treatment by corticoids severe cardiac pathology patients already treated by statins or treated by fibrates, cyclosporine history of muscular toxicities when treated by fibrates or by statins Personal or familial history of hereditary muscular pathology Plasmatic CPK >3 UNL patient already included in another therapeutic trial with an experimental drug, pregnant patient or susceptible to pregnancy or breast feeding (patients in age to give birth must be placed under efficient contraception), a social or psychological condition that does not allow a positive patient's participation in the treatment and necessary medical follow-up to be envisaged, the patient is under legal restrained or tutelage.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Pravastatin<br>Pravastatin : 40mg/day during 12 months | Drug: Pravastatin<br>* Pravastatin 40mg/day during 12 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| regression of radio-induced fibrosis (RIF) evaluated by high frequency ultrasound | a decrease of the maximal thickness more than 30% compared to RIF before treatment. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibrosis grade according to NCI-CTCAE v4 toxicities scale. |  | 12 months | 
| Quality of life | VQ-Dermato scale | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cutaneous radioinduced fibrosis