A Comparative Study of Pravastatin vs Placebo as Primary Prevention of Severe Subcutaneous Breast Fibrosis in Hyper-radiosensitive Identified Patients With Breast Cancer

NCT04385433 | Terminated Phase 3 DMC

• 1 other identifier: PROICM 2019-11 PRA
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 7

Brief Summary

• Interventional trials aim at preventing severe RIF occurrence in BC patients selected by individual radiosensitivity: PRAVAPREV-01 will be the first interventional double blind trial that will offer a personalised strategy to breast cancer patients who will be treated with adjuvant RT after breast conserving surgery:
• By assessing individual risk of severe RIF development
• By offering a statin targeted therapy to the high-risk patients identified.

Conditions

Breast Cancer

Keywords

radiotherapy

Outcome Measures

Primary Outcomes (1)

• 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

  2-year breast fibrosis-free survival (BF-FS) rate

  From randomization to 24 months

Secondary Outcomes (12)

• Impact of this personalized radiotherapy on Acute toxicities

  from randomization to 3 months

• Impact of this personalized radiotherapy on late toxicities

  from randomization to 3 years

• Adverse events due to Pravastatine

  from randomization to 2 years

• Local recurrence

  at 1, 2, 3, 5 and 10 years

• Relapse free survival (RFS)

  at 1, 2, 3, 5 and 10 years

Study Arms (2)

EXPERIMENTAL GROUP

EXPERIMENTAL

RADIOTHERAPY + PRAVASTATIN

Drug: EXPERIMENTAL ARM; Radiation: Standard adjuvant whole breast radiotherapy (50Gy/ 25 fractions to whole breast) followed or not by a boost to tumor bed (16Gy/ 8 fractions)

CONTROL GROUP

PLACEBO COMPARATOR

RADIOTHERAPY + PLACEBO

Other: CONTROL GROUP; Radiation: Standard adjuvant whole breast radiotherapy (50Gy/ 25 fractions to whole breast) followed or not by a boost to tumor bed (16Gy/ 8 fractions)

Interventions

EXPERIMENTAL ARM DRUG

Patients in the experimental arm will receive: * Daily pravastatin (40mg/d) during 12 months (pravastatin initiation: first day of radiotherapy). * Standard adjuvant whole breast radiotherapy (50Gy/ 25 fractions to whole breast) followed or not by a boost to tumor bed (16Gy/ 8 fractions).

Also known as: pravastatin group

EXPERIMENTAL GROUP

CONTROL GROUP OTHER

Patients in the standard arm will receive: * Daily placebo during 12 months (placebo initiation: first day of radiotherapy) * Standard adjuvant whole breast radiotherapy (50Gy/ 25 fractions to whole breast) followed or not by a boost to tumor bed (16Gy/ 8 fractions).

Also known as: placebo group

CONTROL GROUP

Standard adjuvant whole breast radiotherapy (50Gy/ 25 fractions to whole breast) followed or not by a boost to tumor bed (16Gy/ 8 fractions) RADIATION

Radiotherapy will last 5 weeks during treatment by Pravastatine or Placebo

CONTROL GROUP; EXPERIMENTAL GROUP

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women ≥ 18 years old (no age limit)
• Conservative breast cancer surgery
• High risk level of breast fibrosis identified by the centralized NovaGray RILA Breast® test
• Invasive carcinoma : pT1-T2; pN0 (negative sentinel nodes or axillary nodes dissection) and/or Ductal in situ carcinoma
• Negative surgical margins
• Indication of whole breast irradiation only (with or without boost to tumor bed according to physician discretion)
• Only 3D-conformal RT will be allowed
• Blood sample allowing pravastatin use : serum creatinine ≤ 130 µmol/l; ASAT and ALAT≤ 2N; total bilirubin ≤ 1.5N; CK MM levels \< 3 x ULN for women ≥ 70 years (at least 15 days before randomization).
• Negative pregnancy test in women of childbearing potential (β-HCG dosage ≤ 7 days prior to randomization), an adequate contraception should be used from the beginning of the study to 4 weeks after last treatment dose. The women not of reproductive potential are female patients who are postmenopausal (with a minimum of one year without menstruation and without alternative medical cause) or permanently sterilized: e.g., tubal occlusion, hysterectomy, bilateral salpingectomy).
• Must be geographically accessible for follow-up
• Written and dated informed consent
• Affiliated to the French national social security system

You may not qualify if:

• 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
• Patients with distant metastases
• Indications of node irradiation (axillar or supraclavicular or mammary chain)
• T3-4 or N1-3 breast cancer
• Patients who underwent radical mastectomy
• Neoadjuvant systemic therapy (chemotherapy, hormonotherapy, targeted therapies)
• 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
• Patients with other non-malignant systemic diseases (cardiovascular, renal, hepatic, lung embolism, infection etc.) which would disrupt extended follow-up
• Untreated hypothyroidism
• 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 pravastatine, or any constituent of the product.
• Patient with alcohol misuse.

Sponsors & Collaborators

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

Study Sites (7)

Centre Azuréen de Cancérologie

Mougins, Alpes-Maritimes, 06250, France

Location

Clinique Sainte-Anne

Strasbourg, Bas-Rhin, 67000, France

Location

Centre Hospitalier de Brive

Brivé, Corrèze, 19100, France

Location

Centre Georges-François Leclerc

Dijon, Côte d'Or, 21079, France

Location

Icm Val D'Aurelle

Montpellier, Herault, 34298, France

Location

Centre Hospitalier Universitaire Lyon Sud

Lyon, 69000, France

Location

Centre Hospitalier Princesse Grace

Monaco, 98000, Monaco

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Céline Bourgier, MD

  ICM Co. Ltd.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: May 13, 2020
• Study Start: December 4, 2020
• Primary Completion: April 27, 2023
• Study Completion: April 27, 2023
• Last Updated: August 24, 2023

Record last verified: 2023-05

Locations

FR (6); MO (1)