Clinical Trial: NCT04601116 - My Cancer Genome

NCT04601116

Description:

Given the compelling evidence supporting a protective effect of statins on breast cancer recurrence, calls for prospective clinical trials have been expressed. In this trial - the MASTER trial - we hypothesize that the addition of statin treatment to the current breast cancer treatment will improve the prognosis of women with early breast cancer. This trial is designed as follows: a randomized, multicenter, double-blind, placebo-controlled comparison of standard (neo)adjuvant therapy plus placebo versus standard (neo)adjuvant therapy plus atorvastatin in patients with early breast cancer.

Related Conditions:

Breast Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04601116

Trial Eligibility

Document

Title

Brief Title: The MASTER Study (MAmmary Cancer STatin ER Positive Study)
Official Title: A Randomized, Multicenter, Double-blind, Placebo-controlled Comparison of Standard (Neo)Adjuvant Therapy Plus Placebo Versus Standard (Neo)Adjuvant Therapy Plus Atorvastatin in Patients With Early Breast Cancer

Clinical Trial IDs

ORG STUDY ID: SBMASTER
SECONDARY ID: 2019-002508-42
NCT ID: NCT04601116

Conditions

Breast Cancer Female
Estrogen Receptor Positive Tumor

Interventions

Drug	Synonyms	Arms
Atorvastatin 80 Mg Oral Tablet		Atorvastatin 80 Mg Oral Tablet
Placebo oral tablet		Placebo

Purpose

Detailed Description

      Cholesterol-lowering drugs such as statins are currently used to lower cholesterol levels and
      prevent cardiovascular events. Statins have, however, received substantial scientific
      attention as cancer-inhibiting drugs. Previous findings were recently supported in a
      large-scaled study again demonstrating the beneficial effects of statins on breast cancer
      outcome this time nested within a large, international, randomized clinical trial of modern
      adjuvant cancer therapy. Given the compelling evidence supporting a protective effect of
      statins on breast cancer recurrence, calls for prospective clinical trials have been
      expressed. In this trial - the MASTER trial - we hypothesize that the addition of statin
      treatment to the current breast cancer treatment will improve the prognosis of women with
      early breast cancer. Thus, the primary objective of the MASTER trial is to determine the
      clinical efficacy of the statin - atorvastatin - as measured by invasive disease-free
      survival among patients with primary breast cancer.

      The trial is nationwide throughout Denmark and a total of 3,360 women are to be included in
      the trial. Women eligible for the trial have been diagnosed with an estrogen receptor
      positive breast cancer and are candidates for systemic cancer therapy, either prior to or
      following breast surgery. Upon eligibility and signed informed consent, trial participants
      will be randomized in a 1:1 manner to either standard treatment and atorvastatin 80 mg/day or
      standard treatment and placebo. The randomization is blinded. The treatment with atorvastatin
      or placebo will continue for two years unless side effects are experienced and further
      treatment with atorvastatin or the placebo is deemed inadequate. The standard treatment will
      of course continue as planned. The trial participants will follow the standard clinical
      routines in terms of follow-up and in addition they are asked to fill in questionnaires, i.e.
      regarding potential side effects or new events or diagnoses, up to ten years following
      inclusion. Potential breast cancer recurrences are hereby identified and a follow-up of at
      least 61/2 years will be required for the trial the demonstrate the estimated clinical
      difference between the randomized groups of patients.

Trial Arms

Name	Type	Description	Interventions
Atorvastatin 80 Mg Oral Tablet	Active Comparator	Atorvastatin 80 mg tablets per day for 2 years	Atorvastatin 80 Mg Oral Tablet
Placebo	Placebo Comparator	Placebo tablets 1 per day for 2 years.	Placebo oral tablet

Eligibility Criteria

        Patients must meet ALL of the following criteria to be eligible for randomization:

        Inclusion Criteria:

          1. Women with estrogen receptor positive breast cancer who are candidates for
             (neo)adjuvant systemic therapy OR have received ≤3 years of adjuvant endocrine
             therapy.

          2. Age > 18 years.

          3. Performance status of ECOG ≤ 2.

          4. Prior to patient registration, written informed consent must be given according to
             ICH/GCP, and national/local regulations.

        Patients meeting ANY one of the following criteria are not eligible:

        Exclusion Criteria:

          1. History of any prior (ipsi- and/or contralateral) invasive breast carcinoma.

          2. Ongoing (prevalent) cholesterol-lowering therapy (statins, fibrates, ezetimibe, PCSK9
             inhibitors). If so, the patient can be enrolled in the observational arm.

          3. Evidence of hepatic dysfunction (alanine aminotransferase level more than three times
             the upper limit of the normal range) or renal dysfunction (creatinine level more than
             three times the upper limit of the normal range).

          4. Predisposing factors for rhabdomyolysis, including hypothyroidism, reduced renal
             function, any muscle - or liver disease, or excessive alcohol consumption AND creatine
             kinase (CK) measured to less than five times the upper limit (CK only measured in case
             of predisposing factors).

          5. No current medication with potent CYP3A4-inhibitors (e.g. ketokonazole, erythromycin)
             or gemfibrozile, cyclosporin or danazol.

          6. Pregnancy or breast-feeding.

          7. Psychological, familial, sociological or geographical condition potentially hampering
             compliance with the study protocol and follow-up schedule; these conditions will be
             discussed with the patient before registration in the trial.

          8. History of allergic reactions attributed to compounds of similar chemical or
             biological composition to atorvastatin.

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Female
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Invasive disease-free survival
Time Frame:	10 years
Safety Issue:
Description:	Invasive disease-free survival (IDFS), defined as the time from randomization until the date of the first occurrence of one of the following events: Ipsilateral invasive breast tumor recurrence: invasive breast cancer involving the same breast parenchyma as the original primary. Regional invasive breast cancer recurrence: Invasive breast cancer in the axilla, regional lymph nodes, chest wall, and skin of the ipsilateral breast. Distant recurrence: Metastatic disease-breast cancer that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. Death attributable to any cause, including breast cancer, non-breast cancer, or unknown cause. Contralateral invasive breast cancer. Second primary non-breast invasive cancer.

Secondary Outcome Measures

Measure:	Distant-recurrence free interval
Time Frame:	10 years
Safety Issue:
Description:	Distant-recurrence free interval defined as time from inclusion to first distant recurrence including associations with first site of recurrence.

Measure:	Recurrence-free interval
Time Frame:	10 years
Safety Issue:
Description:	Recurrence-free interval including associations with first site of recurrence

Measure:	Overall survival.
Time Frame:	10 years
Safety Issue:
Description:	Overall survival.

Measure:	Incidence of Treatment-Emergent Adverse Events as assessed by CTC-AE, 5.0
Time Frame:	10 years
Safety Issue:
Description:	Incidence of Treatment-Emergent Adverse Events as assessed by CTC-AE, 5.0

Measure:	Cardiac death-free interval
Time Frame:	10 years
Safety Issue:
Description:	Cardiac death-free interval. Cardiac death is defined as: Definitive cardiac death due to heart failure, myocardial infarction or documented primary arrhythmia. Probable cardiac death: Probable cardiac death defined as sudden, unexpected death within 24 hours of a definite or probable cardiac event (e.g., syncope, cardiac arrest, chest pain, infarction, arrhythmia) without documented etiology.

Measure:	Co-morbidity
Time Frame:	10 years
Safety Issue:
Description:	Co-morbidity incidence beyond cardiovascular events during follow-up including diagnoses such as diabetes mellitus.

Details

Phase:	Phase 3
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	Aarhus University Hospital

Trial Keywords

Breast Cancer
Atorvastatin
Estrogen Receptor Positiv Tumor
Adjuvant therapy
Neoadjuvant
Statin

Last Updated

January 14, 2021

Clinical Trials /

The MASTER Study (MAmmary Cancer STatin ER Positive Study)