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

NCT01268202 | Completed Phase 2

• 1 other identifier: CSET 1383 - PRAVACUR
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 3

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.

Conditions

Fibrosis

Keywords

cutaneous radioinduced fibrosis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Fibrosis grade according to NCI-CTCAE v4 toxicities scale.

  12 months

• Quality of life

  12 months

Study Arms (1)

Pravastatin

EXPERIMENTAL

Pravastatin : 40mg/day during 12 months

Drug: Pravastatin

Interventions

Pravastatin DRUG

Pravastatin 40mg/day during 12 months

Pravastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gustave Roussy, Cancer Campus, Grand Paris: lead
• Ministry of Health, France: collaborator

Study Sites (3)

Centre Val d'Aurelle

Montpellier, 34298, France

Location

Hôpital Européen Georges Pompidou

Paris, 75015, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Related Publications (1)

• Bourgier C, Auperin A, Rivera S, Boisselier P, Petit B, Lang P, Lassau N, Taourel P, Tetreau R, Azria D, Bourhis J, Deutsch E, Vozenin MC. Pravastatin Reverses Established Radiation-Induced Cutaneous and Subcutaneous Fibrosis in Patients With Head and Neck Cancer: Results of the Biology-Driven Phase 2 Clinical Trial Pravacur. Int J Radiat Oncol Biol Phys. 2019 Jun 1;104(2):365-373. doi: 10.1016/j.ijrobp.2019.02.024. Epub 2019 Feb 15.

  PMID: 30776452 DERIVED

Related Links

• Institut Gustave Roussy

MeSH Terms

Conditions

Fibrosis

Interventions

Pravastatin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Study Officials

• Sofia Rivera, MD

  Gustave Roussy, Cancer Campus, Grand Paris

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2010
• First Posted: December 29, 2010
• Study Start: December 17, 2010
• Primary Completion: April 18, 2019
• Study Completion: April 18, 2019
• Last Updated: June 13, 2019

Record last verified: 2019-06

Locations

FR (3)