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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Gustave Roussy, Cancer Campus, Grand Paris
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier:
NCT01268202
First received: December 28, 2010
Last updated: January 16, 2014
Last verified: January 2014
  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

Resource links provided by NLM:


Further study details as provided by Gustave Roussy, Cancer Campus, Grand Paris:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 2014
Estimated Primary Completion Date: June 2014 (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
Criteria

Inclusion Criteria:

  1. Grade >= 2 cutaneous and/or subcutaneous fibrosis (NCI-CTCAE v4 toxicities scale) revealed from 6 to 24 months after head and neck radiotherapy.
  2. Head and neck cancers treated by radiation therapy +/- chemotherapy, +/- surgery, with no evidence of progressive disease.
  3. Age >= 18
  4. Karnofsky PS ≥ 70
  5. normal renal function (plasmatic creatinine <= 130 micromol/l), normal cholesterol, normal hepatic function (total bilirubin <= 1.5 UNL, SGOT and SGPT <= 2 UNL)
  6. Written informed consent of the patient.

Exclusion Criteria:

  1. any chronic treatment by corticoids
  2. severe cardiac pathology
  3. patients already treated by statins or treated by fibrates, cyclosporine
  4. history of muscular toxicities when treated by fibrates or by statins
  5. Personal or familial history of hereditary muscular pathology
  6. Plasmatic CPK >3 UNL
  7. patient already included in another therapeutic trial with an experimental drug,
  8. pregnant patient or susceptible to pregnancy or breast feeding (patients in age to give birth must be placed under efficient contraception),
  9. 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,
  10. the patient is under legal restrained or tutelage.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01268202

Contacts
Contact: Sofia Rivera, MD sofia.rivera@gustaveroussy.fr
Contact: Aurélie Abou Lovergne aurelie.aboulovergne@gustaveroussy.fr

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         
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
Ministry of Health, France
Investigators
Study Chair: Sofia Rivera, MD Gustave Roussy, Cancer Campus, Grand Paris
  More Information

No publications provided

Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT01268202     History of Changes
Other Study ID Numbers: CSET 1383 - PRAVACUR
Study First Received: December 28, 2010
Last Updated: January 16, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Gustave Roussy, Cancer Campus, Grand Paris:
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 July 26, 2014