Improving Theempowerment in Patients With Severe Breast Fibrosis Radio-induced Treated by Pravastatin : Benefit of e-PROs (Electronic " Patient Reported Outcome ") on Breast-related Quality of Life (PRAVACUR-02)

Conserving surgery followed by adjuvant radiotherapy is currently the therapeutic standard for patient with Breast Cancer. Symptoms are common among patients receiving this treatment. Ten percent of them will develop severe and chronic radio-induced toxicities, such as breast radio-induced-fibrosis impairing their quality of life (QoL). Yet, paying attention to symptom improves the empowerment and psychological adjustment to the disease. Web-based systems that can provide electronic-Patient reported Outcomes (e-PRO) have been shown to prompt clinicians to intensify symptom management, to improve symptom control, and to enhance patient-clinician communication patient satisfaction, as well as well-being.Benefits of systems to elicit e-PRO improve reliable measure of health-related quality of life (QoL) remains discussed.

To date, there are few specific treatments for these severe radio-induced fibrosis except the antifibrotic combinaison Pentoxifylline/Vitamin E with inconsistent result.

Since 2000, we and others have developed a mechanistic approach modulating the severity of RIF by targeting the Rho/ROCK/CTGF pathway, especially by inhibiting Rho activation by pravastatin. Our preclinical data, then followed by the Phase II PRAVACUR-01 trial, concluded that the use of pravastatin has an anti-fibrotic action on different experimental models and reduces the severity of the grade of fibrosis in 50% of patients.

Patients can now benefit from this new anti-fibrotic agent.

Taken as a whole, these data encourage combining both drug (pravastatin) and non-pharmacological intervention , in particular e-PRO, in the RIF management.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: e-PRO Intervention; Drug: Pravastatin

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: BOURGIER MD CELINE; Phone Number: 0467612354; Email: celine.bourgier@ivm.unicancer.fr

Study Locations

• France
  • Montpellier, France, 34298
    • Recruiting
    • ICM Val d'Aurelle
    • Contact: BLEUSE Jean-pierre; Phone Number: 00467613102; Email: jean-pierre.bleuse@icm.unicancer.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Breast cancer patients treated by conserving surgery followed by adjuvant RT
2. Over 18 years old
3. At least, grade 2 breast RIF
4. Treatment planning data of breast cancer radiotherapy must be available

5. The following laboratory values obtained ≤ 15 days prior to randomization:

   Serum creatinine ≤ 130 µmol/l; ASAT and ALAT≤ 2N; total bilirubin ≤ 1.5N; CK levels < 3 x ULN, only for the women ≥ 70 years

6. Negative pregnancy test (β-HCG dosage) in women of childbearing potential (women not of reproductive potential are female patients who are postmenopausal or permanently sterilized: e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
7. Patient without contraindication to treatment with pravastatin
8. Signed and dated written consent
9. Patient must be affiliated to a French Social Security System

Exclusion Criteria:

1. Any breast cancer recurrences
2. Current treatment by : statin, fibrate, ciclosporin, systemic fusidic acid, long-term treatment by corticoids
3. History of muscular dystrophy diseases or chronic and/or hereditary muscular diseases
4. Untreated hypothyroidism
5. Serum creatinine > 130 µmol/l; ASAT and ALAT > 2N; total bilirubin > 1.5N
6. CK levels > 3 x ULN in women over 70 years
7. Known positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAG) or hepatitis C virus (HCV) antibody
8. Pregnant or breastfeeding women
9. Women of childbearing potential who are unwilling to employ adequate contraception, from the beginning of the study to 4 weeks after last treatment dose
10. Known hypersensitivity to pravastatin, or any constituent of the product.
11. Patient with alcohol misuse.
12. Patients treated with systemic investigational drugs within the past 30 days
13. Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EXPERIMENTAL GROUP; ePRO intervention + PRAVASTATINE treatment	Other: e-PRO Intervention; Statements of symptoms and patients' health status (PROs) will be collected via a web interface, including access and use in patients with burden symptoms. The platform will include four items concerning 7 side effects of fibrosis of grade > 2 in breast cancer. Patients will be encouraged to evaluate on a 5-point Likert scale the frequency, the intensity and the repercussions on the daily life of some symptoms during the last 7 days, in particular on: general pain; anxiety; sadness; texture of the treated breast; Patients will also be invited to express themselves on the severity of two other symptoms of their choice, to their worst degree, by listing and rating them on a 5-point scale ranging from "None" to "Very severe" Finally, the aesthetic impact will be evaluated by patients on a visual analogue scale (VAS) of 0 to 100mm; Other Names: Electronic-Patient Reported Outcomes; Drug: Pravastatin; All patients will take Pravastatin 40 mg per day (From Day 0 to Month 12).
Other: CONTROL GROUP; PRAVASTATINE treatment ( without ePRO)	Drug: Pravastatin; All patients will take Pravastatin 40 mg per day (From Day 0 to Month 12).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluate the benefit on breast-related quality of life of systematic e-PROs	The BRQoL improvement rate at 12 months, compared with baseline, defined as: an improvement of 5 points (or more) of the score assessed by the functional scale "body image" of the QLQ-BR23 (summary score including the items # 39-42), or; a reduction of 5 points (or more) of the score on the symptom scale "breast symptoms" assessed by the QLQ-BR23 (summary score including the items # 51- 53).	From randomization to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
evaluate the patients'HRQoL	defined by the Health-related quality of life assessed by the EORTC QLQ-C30 and its module BR23	at baseline;12,24, 36, 48 and 60 months
estimate the use of antidepressants	defined by the rate and dose of used antidepressants	From randomization to 12 months
estimate the use of analgesics	defined by the rate and dose of used analgesics	From randomization to 12 months
estimate the use of anxiolytics	defined by the rate and dose of used anxiolytics	From randomization to 12 months
Assess the levels of psychological distress	assessed by (HADS) Scale : score {min :0 (no Distress) --- max :21 ( Hight Distress) }	at baseline; at 12, 24, 36, 48 and 60 months
monitor the e-PROs alerts in the experimental group	Timing of the e-PROs alerts and the care management (phone call or planning of a consultation, treatment initiation)	From randomization to 12 months
characterise the evaluation of the side effects linked to RIF in the experimental group	Evolution of the 7 different e-PROs scores across time (general pain { 0 (no pain)- 4 (high pain)}, anxiety{ 0 (no anxiety)- 4 (high anxiety)}, sadness { 0 (no sad)- 4 (high sad)}, texture of the treated breast{ 0 (no sweeling)- 4 (high sweeling)}, two other symptoms assessed by the PRO-CTCAE scales { 0 (none)- 4 (severe)}, and scores of aesthetic impact assesses by a Visual Analog Scale{ 0 (no impact)- 100 (max impact)}	From randomization to 12 months
characterise the modifications of the patients' management in the experimental group	Number of hospital emergency visits or hospitalizations	From randomization to 12 months
evaluate the anti-fibrotic efficacy of pravastatin	Number of supplementary consultations	From randomization to 12 months
evaluate the pravastatin safety	Regression rate of at least 1 grade of fibrosis (follow-up of fibrosis grade evolution since inclusion)	From randomization to 12 months
estimate the relapse-free survival	Relapse-free survival defined as the time from the date of randomization to the date of the first observed oncological event such as local, ipsilateral, regional or metastatic recurrence or death for any cause	Until study completion: 5 years

Collaborators and Investigators

• Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2020
• Primary Completion (Estimated): June 30, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: April 14, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 23, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pravastatin
• Other Study ID Numbers: PROICM 2019-02 PRA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No