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

• Sponsor: Gustave Roussy, Cancer Campus, Grand Paris (Other)
• Overall Status: Completed
• CT.gov ID: NCT01268202
• Collaborator: Ministry of Health, France (Other)
• Enrollment: 61
• Locations: 3
• Arm: 1
• Actual Duration (Months): 100
• Patients Per Site: 20.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Fibrosis	Drug: Pravastatin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 61 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Curative Efficacy of Pravastatine in Patients Presented Delayed Cutaneous and Subcutaneous Radio-induced Fibrosis
• Actual Study Start Date: Dec 17, 2010
• Actual Primary Completion Date: Apr 18, 2019
• Actual Study Completion Date: Apr 18, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pravastatin Pravastatin : 40mg/day during 12 months	Drug: Pravastatin; Pravastatin 40mg/day during 12 months

Outcome Measures

Primary Outcome Measures

1. regression of radio-induced fibrosis (RIF) evaluated by high frequency ultrasound [12 months]

   a decrease of the maximal thickness more than 30% compared to RIF before treatment.

Secondary Outcome Measures

1. Fibrosis grade according to NCI-CTCAE v4 toxicities scale. [12 months]

2. Quality of life [12 months]

   VQ-Dermato scale

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Centre Val d'Aurelle	Montpellier		France	34298
2	Hôpital Européen Georges Pompidou	Paris		France	75015
3	Institut Gustave Roussy	Villejuif		France	94805

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Institut Gustave Roussy

Publications

None provided.

• Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
• ClinicalTrials.gov Identifier: NCT01268202
• Other Study ID Numbers: CSET 1383 - PRAVACUR
• First Posted: Dec 29, 2010
• Last Update Posted: Jun 13, 2019
• Last Verified: Jun 1, 2019

• Keywords provided by Gustave Roussy, Cancer Campus, Grand Paris: cutaneous radioinduced fibrosis
• Additional relevant MeSH terms: Fibrosis; Pravastatin

Study Results

No Results Posted as of Jun 13, 2019