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.
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
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.
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. | |
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