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

NCT02958852 | Completed Phase 2

• 1 other identifier: OKFE 15-ABC-SE
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 1

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.

Conditions

Breast Cancer

Keywords

Breast Cancer; Endocrine Treatment; Atorvastatin; Mechanisms of Resistance; Statins; Fulvestrant; Circulating Tumor Cells; Statins and Endocrine Treatment; Tumor Marker Expression; ER+ Metastatic Breast Cancer; Circulating Tumor DNA; Cholesterol

Outcome Measures

Primary Outcomes (1)

• Clinical benefit rate.

  Clinical benefit rate (CBR), defined as the proportion of all randomly assigned patients who have the best overall response a complete response, a partial response, or stable disease up to 24 weeks following first-line letrozole treatment alone or in combination with atorvastatin.

  6 months after the last patient has been randomly assigned.

Secondary Outcomes (6)

• Progression free survival.

  6 months after the last patient has been randomly assigned. Data cut off, 15th October 2020.

• Objective response rate.

  6 months after the last patient has been randomly assigned. Data cut off, 15th October 2020.

• Time to progression.

  From date of treatment start until the date of first documented progression. Data cut off, 15th October 2020.

• Duration of Clinical benefit.

  6 months after the last patient has been randomly assigned. Data cut off, 15th October 2020.

• Overall survival.

  6 months after the last patient has been randomly assigned. Data cut off, 15th October 2020.

Study Arms (3)

Letrozole

ACTIVE COMPARATOR

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.

Drug: Letrozole

Letrozole+Atorvastatin

EXPERIMENTAL

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.

Drug: Letrozole and atorvastatin

Fulvestrant

OTHER

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

Drug: Fulvestrant

Interventions

Letrozole DRUG

Daily orally

Letrozole

Letrozole and atorvastatin DRUG

Daily orally

Letrozole+Atorvastatin

Fulvestrant DRUG

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

Fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Women with confirmed ER positive/HER2 negative metastatic breast cancer, including locally advanced stage IV disease, requiring systemic endocrine treatment.
• Age \> 18 years.
• Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2.
• 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.
• 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.
• 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.
• 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.
• Signed informed consent according to International Conference on Harmonization /Good Clinical Practice, and national/local regulations.
• 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.
• 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.

You may not qualify if:

• Brain as the only site of metastatic breast cancer.
• 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.
• 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.
• 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.
• History of hemorrhagic stroke.
• Pregnancy or breast-feeding.
• Untreated psychiatric disorders that will impair the patient's ability to comply with study treatment or protocol.
• History of allergic reactions attributed to compounds of similar chemical or biological composition to either of the study drugs.

Sponsors & Collaborators

• Lund University Hospital: lead
• South Sweden Breast Cancer Group: collaborator

Study Sites (1)

Lund University Hospital, Department of Oncology

Lund, 221 85, Sweden

Location

MeSH Terms

Conditions

Breast Neoplasms; Neoplastic Cells, Circulating

Interventions

Letrozole; Atorvastatin; Fulvestrant

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Neoplasm Metastasis; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrroles; Heptanoic Acids; Fatty Acids; Lipids; Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Signe Borgquist, MD, PhD

  Lund University Hospital, Department of Oncology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2016
• First Posted: November 8, 2016
• Study Start: January 2, 2025
• Primary Completion: January 2, 2025
• Study Completion: January 15, 2025
• Last Updated: September 10, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)