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

Overview

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.

Interventions

• 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 * text
• Drug Pravastatin
  All patients will take Pravastatin 40 mg per day (From Day 0 to Month 12).

Primary outcome measures

• evaluate the benefit on breast-related quality of life of systematic e-PROs [Time frame: From randomization to 12 months]

Secondary outcome measures (11)

• evaluate the patients'HRQoL [Time frame: at baseline;12,24, 36, 48 and 60 months]
• estimate the use of antidepressants [Time frame: From randomization to 12 months]
• estimate the use of analgesics [Time frame: From randomization to 12 months]
• estimate the use of anxiolytics [Time frame: From randomization to 12 months]
• Assess the levels of psychological distress [Time frame: at baseline; at 12, 24, 36, 48 and 60 months]
• monitor the e-PROs alerts in the experimental group [Time frame: From randomization to 12 months]
• characterise the evaluation of the side effects linked to RIF in the experimental group [Time frame: From randomization to 12 months]
• characterise the modifications of the patients' management in the experimental group [Time frame: From randomization to 12 months]
• evaluate the anti-fibrotic efficacy of pravastatin [Time frame: From randomization to 12 months]
• evaluate the pravastatin safety [Time frame: From randomization to 12 months]
• estimate the relapse-free survival [Time frame: Until study completion: 5 years]

Eligibility criteria

Inclusion criteria

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

• 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).
• Patient without contraindication to treatment with pravastatin
• Signed and dated written consent
• Patient must be affiliated to a French Social Security System

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

France · 1 center

• ICM Val d'Aurelle — Montpellier

Identifiers

NCT: NCT04356209 · PROICM 2019-02 PRA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗