Curative Efficacy of Pravastatine in Patients Presented Delayed Cutaneous and Subcutaneous Radio-induced Fibrosis (PRAVACUR)
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Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Fibrosis |
Drug: Pravastatin |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Curative Efficacy of Pravastatine in Patients Presented Delayed Cutaneous and Subcutaneous Radio-induced Fibrosis |
- regression of radio-induced fibrosis (RIF) evaluated by high frequency ultrasound [ Time Frame: 12 months ] [ Designated as safety issue: No ]a decrease of the maximal thickness more than 30% compared to RIF before treatment.
- Fibrosis grade according to NCI-CTCAE v4 toxicities scale. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
- Quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]VQ-Dermato scale
| Estimated Enrollment: | 55 |
| Study Start Date: | December 2010 |
| Estimated Study Completion Date: | June 2013 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Pravastatin
Pravastatin : 40mg/day during 12 months
|
Drug: Pravastatin
Pravastatin 40mg/day during 12 months
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations| France | |
| Centre Val d'Aurelle | Not yet recruiting |
| Montpellier, France, 34298 | |
| Contact: David AZRIA, MD | |
| Principal Investigator: David AZRIA, MD | |
| Hôpital Européen Georges Pompidou | Not yet recruiting |
| Paris, France, 75015 | |
| Contact: Philippe GIRAUD, MD | |
| Principal Investigator: Philippe GIRAUD, MD | |
| Institut Gustave Roussy | Recruiting |
| Villejuif, France, 94805 | |
| Contact: Céline BOURGIER, MD, PhD 33 1 42 11 49 31 bourgier@igr.fr | |
| Contact: Anne AUPERIN, MD, PhD 33 1 42 11 54 99 auperin@igr.fr | |
| Principal Investigator: Céline BOURGIER, MD, PhD | |
| Principal Investigator: | Céline BOURGIER, MD, PhD | Institut Gustave Roussy |
More Information
No publications provided
| Responsible Party: | Institut Gustave Roussy |
| ClinicalTrials.gov Identifier: | NCT01268202 History of Changes |
| Other Study ID Numbers: | CSET 1383 - PRAVACUR |
| Study First Received: | December 28, 2010 |
| Last Updated: | February 5, 2013 |
| Health Authority: | France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis) |
Keywords provided by Institut Gustave Roussy:
|
cutaneous radioinduced fibrosis |
Additional relevant MeSH terms:
|
Fibrosis Pathologic Processes Pravastatin Anticholesteremic Agents Hypolipidemic Agents Antimetabolites |
Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Lipid Regulating Agents Therapeutic Uses Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 19, 2013