E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Radio-induced fibrosis in breast cancer |
patientes présentant un risque élevée de fibrose radio-induite dans le cancer du sein |
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E.1.1.1 | Medical condition in easily understood language |
Radio-induced fibrosis in breast cancer |
patientes présentant un risque élevée de fibrose radio-induite dans le cancer du sein |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the impact of Pravastatin on the occurrence of grade ≥2 breast fibrosis in a selected breast cancer patient population considered at high risk of severe breast fibrosis occurrence (identified by the NovaGray RILA Breast® test) vs placebo. |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the impact of this personalized radiotherapy on: - Acute and late toxicities - Safety - Local recurrence - Relapse free survival (RFS) - Breast fibrosis-free survival (BF-FS) - Breast fibrosis-relapse-free survival (BF-RFS) - Overall survival (OS) - Patients’ quality of life (HRQOL) - Cosmetic Outcomes •Evaluate the NovaGray RILA Breast® test performance •Evaluate the feasibility of a new production technique for NovaGray RILA Breast® test •Evaluate the NovaGray RILA Breast® test stability at 12 months
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Searching for a functional association between RILA and Pravastatin-responders, version 1 of 24 july 2019
Objectives : -Assessment of antifibrotic activity of Pravastatine on signaling pathway into radio-induced fibrosis (Rho/ROCK/CTGF, TGF/Smad) from cutaneous superficial biopsy. -Assessment of interaction of pravastatine and ionizing radiation on lymphocyte T and cutaneous fibroblast in particular on the signalling pathways involved in apoptosis and inflammation |
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E.3 | Principal inclusion criteria |
1.Women ≥ 18 years old (no age limit) 2.Conservative breast cancer surgery 3.High risk level of breast fibrosis identified by the centralized NovaGray RILA Breast® test 4.Invasive carcinoma : pT1-T2; pN0 (negative sentinel nodes or axillary nodes dissection) 5.Ductal in situ carcinoma 6.Negative surgical margins 7.Indication of whole breast irradiation only (with or without boost to tumor bed according to physician discretion) 8.Only 3D-conformal RT will be allowed 9.Blood sample allowing pravastatin use : serum creatinine ≤ 130 µmol/l; ASAT and ALAT≤ 2N; total bilirubin ≤ 1.5N; CK levels < 3 x ULN for women ≥ 70 years (at least 15 days before randomization). 10.Negative pregnancy test 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). 11.Must be geographically accessible for follow-up 12.Written and dated informed consent 13.Affiliated to the French national social security system
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E.4 | Principal exclusion criteria |
1.Current treatment by : statin, fibrate, ciclosporin, systemic fusidic acid, long-term treatment by corticoids 2.History of muscular dystrophy diseases or chronic and/or hereditary muscular diseases 3.Patients with distant metastases 4.Indications of node irradiation (axillar or supraclavicular or mammary chain) 5.T3-4 or N1-3 breast cancer 6.Patients who underwent radical mastectomy 7.Neoadjuvant systemic therapy (chemotherapy, hormonotherapy, targeted therapies) 8.Patients with previous or concomitant other (not breast cancer) malignancy within the past 5 years EXCEPT adequately treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix. Patients who have had a previous other malignancy must have been disease free for at least five years 9.Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, infection etc.) which would disrupt extended follow-up 10.Untreated hypothyroidism 11.Serum creatinine > 130 µmol/l; ASAT and ALAT > 2N; total bilirubin > 1.5N 12.CK levels > 5 x ULN in women over 70 years, 13.Known positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAG) or hepatitis C virus (HCV) antibody 14.Pregnant or breastfeeding women 15.women of childbearing potential who are unwilling to employ adequate contraception, from the beginning of the study until the last treatment dose 16.Known hypersensitivity to pravastatine, or any constituent of the product. 17.Patient with alcohol misuse. 18.Patients treated with systemic investigational drugs within the past 30 days 19.Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
breast fibrosis-free survival |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
the time from the date of randomization to the date of the first documented grade ≥2 breast fibrosis |
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E.5.2 | Secondary end point(s) |
1.Incidence of acute (within 3 months during and after radiotherapy) and late side effects 2.Pravastatin tolerance 3.Local recurrence rate 4.Relapse-free survival (RFS) rates 5.Breast fibrosis-free survival (BF-FS) rates 6.Breast fibrosis-relapse-free survival (BF-RFS) rates 7. Overall survival (OS) rates 8.Quality of life 9.Cosmetic outcomes 10.Identification of clinico-biologicals parameters to improve the NovaGray RILA Breast® test performance 11.1 x 4 ml blood sample at baseline for the evaluation of the feasibility of a new production technique for NovaGray RILA Breast® test 12.1 x 4 ml blood sample at 12 months for the evaluation of NovaGray RILA Breast® test stability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.side effects is assessed and graded according to the NCI-CTCAE v5.0 scale.The most severe grade observed during the period per patient will be reported. 2.Tolerance is assessed and graded according to the NCI-CTCAE v5.0 scale 3.Local recurrence rate from the date of randomization to 1, 2, 3, 5 and 10 years 4, 5, 6.the rates are defined as the time from the date of randomization to the date of the first relapse 7. is defined as the time from the date of randomization to the date of death 8. is assessed from the date of randomization to follow-up 5 years 9.is assessed from the date of randomization to 2 years after the end of treatment 10. is defined from the date of randomization to the end of study 11.is assessed at Baseline 12.is assessed at 12 month after randomisation |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Last visit of the last subject included in the study (follow -up 10 years) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 10 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |