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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Other: e-PRO Intervention
* Drug: Pravastatin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EXPERIMENTAL GROUP<br>ePRO intervention + PRAVASTATINE treatment | Other: e-PRO Intervention<br>* 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<br>* Other names: Electronic-Patient Reported Outcomes;Drug: Pravastatin<br>* All patients will take Pravastatin 40 mg per day (From Day 0 to Month 12).<br>|
| Other: CONTROL GROUP<br>PRAVASTATINE treatment ( without ePRO) | Drug: Pravastatin<br>* All patients will take Pravastatin 40 mg per day (From Day 0 to Month 12).<br>|

What is the study measuring?
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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 |