Estrogen receptor positive metastatic or locally advanced inoperable breast cancer. MedDRA version: 20.0 Level: LLT Classification code 10006192 Term: Breast cancer NOS System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Atorvastatin
Product Name: Atorvastatin
Pharmaceutical Form: Tablet
INN or Proposed INN: ATORVASTATIN
CAS Number: 134523-00-5
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
Skåne University Hospital, Department of Oncology
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients diagnosed with ER positive/HER2 negative metastatic breast cancer, including locally advanced stage IV disease, requiring systemic endocrine based treatment. If IHC analysis is not available from the metastatic tissue, the ER and HER2 status is determined from archived primary tumor. 2. Age > 18 years. 3. Performance status of Eastern Cooperative Oncology Group (ECOG) = 2. 4. Metastatic disease must be radiologically or clinically assessable, by means of at least one of the following techniques: clinical examination, computerized tomography (CT), magnetic resonance imaging (MRI), bone scintigraphy or positron emission tomography (PET). Bone metastases alone are allowed. 5. Pre-menopausal patients must consent to undergo either surgical or chemical castration during the duration of the treatment and utilize an effective contraception barrier method. 6. Patient not willing to undergo study specific biopsy from the metastatic site should preferably have enough metastatic tumor sample material archived to perform DNA extraction from formalin fixed paraffin embedded (FFPE) material. 7. Patient must be capable and willing to grant signed informed consent prior to any procedure related with this study as well as to allow access to FFPE biopsies for DNA extraction and for serial CTCs ctDNA analysis. Biopsy of the metastatic site upon progression is not mandatory but desirable. 8. Signed informed consent according to ICH/GCP, and national/local regulations. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 26
Exclusion criteria
Exclusion criteria: 1. Previous treatment for metastatic breast cancer (previous systemic treatment for early breast cancer allowed). 2. Brain as the only site of metastatic breast cancer. 3. Ongoing treatment with statins (e.g. simvastatin, atorvastatin, fluvastatin, lovastatin, pravastatin, or rosuvastatin), anion-exchangers (e.g. colestyramin or colesevelam), fibrates (e.g. gemfibrozil), nicotin-acids (or acipimox) or inhibitors of intestinal cholesterol uptake (e.g. ezitimibe) for the first part of the trial. 4. Evidence of hepatic dysfunction (alanine aminotransferase level more than three times the upper limit of the normal range) or renal dysfunction (creatine kinase level) more than three times the upper limit of the normal range. 5. The patient is unable to pause treatment with anticoagulants/antiagregants prior to biopsy during the recommended times. 6. History of haemorrhagic stroke. 7. Pregnancy or breast-feeding. 8. Untreated psychiatric disorders that will impair the patient’s ability to comply with study treatment or protocol. 9. History of allergic reactions attributed to compounds of similar chemical or biological composition to either of the study drugs.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study superiority of the combination of endocrine based treatment and atorvastatin when compared to endocrine based treatment alone, in terms of clinical benefit rate, Progression Free Survival (PFS), Objective Response Rate (ORR; the proportion of patients with a best overall response- complete response or partial response), Time-To-Progression (TTP), Duration of Clinical Benefit (DCB), Overall Survival (OS). ;Secondary Objective: To establish safety and tolerability of the combination of endocrine based treatment with atorvastatin. To elucidate mechanisms of resistance to endocrine based treatment alone or in combination with statins in ER+ metastatic breast cancer. Translational: 1.To study treatment effects in terms of tumor marker expression in primary tumor, the untreated metastatic tumor, and upon progression 2.To analyse circulating markers measured at inclusion, every third month, and upon progression (e.g. biomarkers of immunology, lipid-metabolism, and endocrine response as well as circulating tumor DNA) 3.To establish a comparison in the genomic profile of the circulating tumor DNA (ctDNA) and the biopsies of the metastatic lesions. Evaluate the findings of the genomic changes in ctDNA before treatment and upon progression to endocrine based treatment with those in the FFPE biopsies obtained at the same time points. ;Primary end point(s): Clinical benefit rate, defined as the proportion of all randomly assigned patients who have the best overall response rate at cut-off time for data analysis following first-line endocrine based therapy alone contrasted to endocrine based therapy plus atorvastatin. Data cut-off time has been pre-specified as 9 months.;Timepoint(s) of evaluation of this end point: Clinical benefit rate, which is defined as the proportion of all randomly assigned patients who have a best overall response of a complete | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) Progression free survival comparing endocrine based treatment alone or endocrine based treatment in combination with atorvastatin in patients with metastatic breast cancer. 2) Objective Response Rate (ORR; the proportion of patients with a best overall response- complete response or partial response). 3) Time-To-Progression (TTP). 4) Duration of Clinical Benefit (DCB). 5) Overall survival. 6) Safety and tolerability ;Timepoint(s) of evaluation of this end point: 1. Progression free survival (PFS) is defined as the time elapsing between the time of random assignment to treatment and the date of the earliest evidence of objective disease progression or death of any cause before documented disease-progression. 2. Time-To-Progression (TTP) defined as time elapsed between date of diagnosis of metastatic disease and date of confirmation of disease progression in the first part of the protocol. 3. Duration of Clinical Benefit (DCB) includes complete response, partial response and disease stabilization. 4. Overall survival defined as the time elapsed from the date of first confirmation of metastatic disease and the date of death from any cause. | — |
Countries
Sweden
Contacts
Public ContactAna Bosch Campos
Skåne University Hospital, Department of Oncology
Outcome results
None listed