A Clinical Trial to Compare Efficacy and Tolerability of Atorvastatin in Addition to Endocrine Treatment With Focus on Mechanisms of Resistance to Endocrine Treatment (Fulvestrant/Aromatase Inhibitors) in Patients With Advanced Breast Cancer

NCT ID: NCT02958852

Last Updated: 2025-09-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-02
• Study Completion Date: 2025-01-15

Brief Summary

A Clinical Trial to Compare Efficacy and Tolerability of Atorvastatin in Addition to Endocrine Treatment with Focus on Mechanisms of Resistance to Endocrine Treatment (fulvestrant/aromatase inhibitors) in Patients With Advanced Breast Cancer.

Detailed Description

A randomized, open-labelled, phase II trial in the first and second-line metastatic treatment setting, comparing standard endocrine treatment (aromatase inhibitor (AI)) with endocrine treatment plus atorvastatin (1:1). Upon progression in the first line setting, and as part of the translational studies on mechanisms of resistance to endocrine therapy, the patients will receive second line endocrine treatment using fulvestrant. Upon progression to first line treatment, patients that were receiving atorvastatin will stop this treatment.

Conditions

Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Letrozole

Confirmed ER positive/HER2 negative metastatic breast cancer, including locally advanced stage IV disease, requiring systemic endocrine treatment, in this case letrozole, 2.5 mg daily until progression of disease. Upon progression of first line, patients will receive second line treatment using fulvestrant.

Group Type: ACTIVE_COMPARATOR

Letrozole

Intervention Type: DRUG

Daily orally

Letrozole+Atorvastatin

Confirmed ER positive/HER2 negative metastatic breast cancer, including locally advanced stage IV disease, requiring systemic endocrine treatment, in this case letrozole, 2.5 mg daily, with the addition of atorvastatin, 40 mg daily until progression of disease. Upon progression of first line, patients will receive second line treatment using fulvestrant.

Group Type: EXPERIMENTAL

Letrozole and atorvastatin

Intervention Type: DRUG

Daily orally

Fulvestrant

Fulvestrant will be used as second line endocrine treatment upon progression on first line with letrozole +/- atorvastatin.

Group Type: OTHER

Fulvestrant

Intervention Type: DRUG

Fulvestrant will be used as second line treatment upon progression on first line treatment with letrozole +/- atorvastatin.

Interventions

Letrozole

Daily orally

Intervention Type: DRUG

Letrozole and atorvastatin

Daily orally

Intervention Type: DRUG

Fulvestrant

Fulvestrant will be used as second line treatment upon progression on first line treatment with letrozole +/- atorvastatin.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Women with confirmed ER positive/HER2 negative metastatic breast cancer, including locally advanced stage IV disease, requiring systemic endocrine treatment.

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 RNA 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 RNA extraction and for serial circulating tumor cells capture. Biopsy of the metastatic site upon progression is not mandatory but desirable.

8. Signed informed consent according to International Conference on Harmonization /Good Clinical Practice, and national/local regulations.

9. Patients currently on first-line treatment with an AI for metastatic breast cancer who cannot participate on the first part of the treatment (taking lowering cholesterol drugs, or already on AIs for metastatic disease when study is opened) can be eligible to enter on the second part to study mechanisms of resistance to fulvestrant once they have progressed to AI.

10. Patients that progress while taking AI as adjuvant treatment, have confirmed hormone receptor+ metastatic breast cancer and are not deemed suitable for first line AI will also be eligible to enter directly in the second part of the study and be treated with fulvestrant up-front.

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.ezetimibe ) 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. Known coagulation disorders or treatment with a 4-hydroxycoumarin derivative is an exclusion criterion for the fulvestrant treated patients.

6. Treatment with anticoagulants other than 4-hydroxycoumarin derivatives or antiplatelet drugs. Patients in treatment with heparin can interrupt treatment 24h prior to biopsies and resume treatment 12h after biopsy has been performed. In case of patients treated with clopidogrel or salicylates, they should be able to interrupt treatment 5-7 days before biopsy and resume 24h after.

7. History of hemorrhagic stroke.

8. Pregnancy or breast-feeding.

9. Untreated psychiatric disorders that will impair the patient's ability to comply with study treatment or protocol.

10. History of allergic reactions attributed to compounds of similar chemical or biological composition to either of the study drugs.

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• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

South Sweden Breast Cancer Group

UNKNOWN

Sponsor Role: collaborator

Lund University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Signe Borgquist, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Lund University Hospital, Department of Oncology

Locations

Lund University Hospital, Department of Oncology

Lund, , Sweden

Countries

Sweden

Other Identifiers

OKFE 15-ABC-SE

Identifier Type: -

Identifier Source: org_study_id