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

Phase 2

Recruiting

• Conditions: Breast Cancer
• Interventions: Drug: Pravastatin; Other: e-PRO Intervention

• Registration Number: NCT04356209
• Lead Sponsor: Institut du Cancer de Montpellier - Val d'Aurelle

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-31
• Study First Submitted: 2020-04-14
• Study First Submitted QC: 2020-04-17
• Study First Posted: 2020-04-22
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-11
• Last Update Posted: 2025-02-12
• Primary Completion: 2026-01-31
• Study Completion: 2031-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 105

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CONTROL GROUP	Pravastatin	PRAVASTATINE treatment ( without ePRO)
EXPERIMENTAL GROUP	e-PRO Intervention	ePRO intervention + PRAVASTATINE treatment
EXPERIMENTAL GROUP	Pravastatin	ePRO intervention + PRAVASTATINE treatment

Primary Outcome Measures

Name	Time	Method
evaluate the benefit on breast-related quality of life of systematic e-PROs	From randomization to 12 months	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).

Secondary Outcome Measures

Name	Time	Method
monitor the e-PROs alerts in the experimental group	From randomization to 12 months	Timing of the e-PROs alerts and the care management (phone call or planning of a consultation, treatment initiation)
evaluate the pravastatin safety	From randomization to 12 months	Regression rate of at least 1 grade of fibrosis (follow-up of fibrosis grade evolution since inclusion)
estimate the relapse-free survival	Until study completion: 5 years	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
estimate the use of antidepressants	From randomization to 12 months	defined by the rate and dose of used antidepressants
Assess the levels of psychological distress	at baseline; at 12, 24, 36, 48 and 60 months	assessed by (HADS) Scale : score {min :0 (no Distress) --- max :21 ( Hight Distress) }
characterise the evaluation of the side effects linked to RIF in the experimental group	From randomization to 12 months	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)}
characterise the modifications of the patients' management in the experimental group	From randomization to 12 months	Number of hospital emergency visits or hospitalizations
evaluate the patients'HRQoL	at baseline;12,24, 36, 48 and 60 months	defined by the Health-related quality of life assessed by the EORTC QLQ-C30 and its module BR23
estimate the use of anxiolytics	From randomization to 12 months	defined by the rate and dose of used anxiolytics
estimate the use of analgesics	From randomization to 12 months	defined by the rate and dose of used analgesics
evaluate the anti-fibrotic efficacy of pravastatin	From randomization to 12 months	Number of supplementary consultations

Trial Locations

Locations (1)

ICM Val d'Aurelle; 🇫🇷 Montpellier, France