Prevention of Female Cancers by Optimization of Selenium Levels in the Organism.

Overview

Hypothesis to be tested: Oral supplementation or diet modifications of selenium to a specified range will be effective in reducing the risk of developing cancer of any type in women with high risk of breast cancer, as compared to placebo.

Full Title of Study: “Prevention of Females Malignancies in Families With Hereditary Breast Cancer by Personalized Optimization of Se Levels in the Organism.”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Prevention
    • Masking: Single (Investigator)
  • Study Primary Completion Date: November 2023

Detailed Description

Primary Objective • To determine the efficacy of oral daily supplementation or diet modification of selenium to an optimal level compared to placebo, in reducing the incidence of any cancers in an at risk population of women over the 60 months of the study. Secondary Objectives – To determine the efficacy of oral daily supplementation or diet modification of selenium to an optimal level compared to placebo, in reducing the incidence of breast cancer in an at risk population of women over the 60 months of the study. – To explore the relationship between the effects of study supplement or diet modifications on cancer risk and genetic factors. The study will have 7000 participants. All the measurements will be performed via blood tests.

Interventions

  • Dietary Supplement: Selenium supplementation or placebo treatment
    • Patients from this group will receive selenium supplement to achieve optimal selenium level
  • Other: Diet modification
    • Patients from this group will have modified diet over the course of the study. Diet modification is aimed to lower selenium concentration in blood.
  • Other: Selenium supplementation or placebo treatment and diet modification
    • In this group patients will receive supplement, placebo or diet modification. The goal is to raise selenium concentration in blood

Arms, Groups and Cohorts

  • Active Comparator: BRCA(+) Selenium deficiency
    • Placebo: 100 Supplement: 100
  • Active Comparator: BRCA(+) Selenium excess
    • Diet modification: 500 Observation: 500
  • Active Comparator: BRCA(-) Selenium deficiency
    • Placebo: 900 Supplement: 900 Diet modification: 900 Observation: 900
  • Active Comparator: BRCA(-) Selenium excess
    • Diet modification: 1100 Observation: 1100
  • Active Comparator: BRCA(+) Selenium excess, age > 50
    • Diet modification: 200 Observation: 200

Clinical Trial Outcome Measures

Primary Measures

  • Development of any new cancer
    • Time Frame: within 60 months of the study
    • Cancer diagnosis will be determined by routine clinical management and confirmed by central pathology review. Cancer-free survival is defined as the period of time between randomization and diagnosis of cancer, or – for patients who do not develop cancer – the period of time between randomization and last contact or death unrelated to cancer.

Secondary Measures

  • Development of new breast cancer
    • Time Frame: within 60 months of the study
    • Cancer diagnosis will be determined by routine clinical management and confirmed by central pathology review. Cancer-free survival is defined as the period of time between randomization and diagnosis of cancer, or – for patients who do not develop cancer – the period of time between randomization and last contact or death unrelated to cancer.
  • Proportion of any other cancers (besides breast cancers) at the end of 60 months
    • Time Frame: within 60 months of the study
    • Cancer diagnosis will be determined by routine clinical management and confirmed by central pathology review. Cancer-free survival is defined as the period of time between randomization and diagnosis of cancer, or – for patients who do not develop cancer – the period of time between randomization and last contact or death unrelated to cancer.

Participating in This Clinical Trial

Inclusion Criteria

  • Sub-group I – BRCA1 mutation carriers 1. Carrier-status of BRCA1 mutation 2. Age >20 years 3. Have a breast magnetic resonance imaging and/or ultrasonography and/or mammography that reveals no disease at maximum 9 months after enrollment 4. Be able to give information consent and sign an informed consent form 5. Be willing to comply with all of the study procedures as per the protocol 6. Be willing to inform researchers about current or any new pregnancy 7. Sub-optimal Se level in the blood Sub-group II – Females from families with hereditary breast cancers but without BRCA1 mutations 1. Age ≥40 years 2. Age ≥20 years for women that have been diagnosed previously with breast cancer 3. Positive medical history of family, matching criteria of hereditary breast/ovarian cancer (HBO) (Appendix 1) 4. No personal history of cancer except for breast cancer and non-melanoma skin cancers 5. Have a breast magnetic resonance imaging/ultrasonography/mammography that reveals no disease at maximum 9 months after enrollment 6. Be able to give information consent and sign an informed consent form 7. Absence of BRCA1 mutations after testing for at least three founder mutations (BRCA1 5382insC, BRCA1 300T/G, BRCA1 4154delA) 8. Be willing to comply with all of the study procedures as per the protocol 9. Be willing to inform researchers about current or any new pregnancy 10. Sub-optimal Se level in the blood Exclusion Criteria:

Sub-group I – BRCA1 mutation carriers 1. Diagnosis of any previous cancer except for breast cancers and non-melanoma skin cancers 2. Absence of a magnetic resonance imaging/ultrasonography/mammography that reveals no disease at maximum 9 months after enrollment 3. Current pregnancy or breast-feeding 4. Optimal Se level in the blood 5. Age <20 years 6. Any medical illness, which, in the investigator's opinion, cannot be adequately controlled with appropriate therapy 7. Participation in any other clinical study involving a medical, surgical, nutritional, or life-style intervention (unless individuals are no longer receiving any intervention and they are in the follow-up phase only) Sub-group II – Females from families with hereditary breast cancers but without BRCA1 mutations 1. Diagnosis of any previous cancer except for breast cancers and non-melanoma skin cancers 2. Absence of magnetic resonance imaging and/or ultrasonography and/or mammography that reveals no disease at maximum 9 months after enrollment 3. Absence of matching pedigree/clinical/molecular criteria of HBO (Appendix 1) 4. Presence of BRCA1 mutation 5. Current pregnancy or breast-feeding 6. Optimal Se level in the blood 7. Age <40 years except for women that have been previously diagnosed with breast cancer 8. Any medical illness, which, in the investigator's opinion, cannot be adequately controlled with appropriate therapy 9. Participation in any other clinical study involving a medical, surgical, nutritional, or life-style intervention (unless individuals are no longer receiving any intervention and they are in the follow-up phase only)

Gender Eligibility: Female

Minimum Age: 21 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Read-Gene S.A.
  • Collaborator
    • National Center for Research and Development, Poland
  • Provider of Information About this Clinical Study
    • Principal Investigator: Lubinski Jan, MD, PhD – Read-Gene S.A.
  • Overall Official(s)
    • Jan Lubiński, MD, PhD, Principal Investigator, Read-Gene S.A.
    • Cezary Cybulski, MD, PhD, Study Chair, Read-Gene S.A.
    • Jacek Gronwald, MD, PhD, Study Chair, Read-Gene S.A.
    • Tomasz Huzarski, MD, PhD, Study Chair, Read-Gene S.A.
    • Anna Jakubowska, MD, PhD, Study Chair,
    • Antoni Morawski, PhD, Study Chair,
    • Ewa Stachowska, PhD, Study Chair, Read-Gene S.A.
    • Edyta Balejko, PhD, Study Chair,
    • Karolina Ertmańska, PhD, Study Chair,

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