Dose Optimization of Rosuvastatin in Early Stage and Metastatic Estrogen Receptor Positive Breast Cancer Patients on Endocrine Therapy

Patients will be treated in a dose escalation scheme to investigate a role for the addition of a statin in the treatment of estrogen receptor positive breast cancer. Patients will take oral rosuvastatin daily. The maximum number of patients evaluable for a DLT is 12. Dosing will be as follows: Cohort 1 - rosuvastatin 20mg, Cohort 2 - rosuvastatin 40mg. The patients will have a total of 4 blood draws and 4 breast biopsies. The breast biopsies will be collected to evaluate cholesterol metabolites and tumor microenvironment characteristics including gene expression profiling and metabolomics. Sampling will occur at study entry, week 4, week 8, and at the time of surgery in early stage patients or at week 16 for metastatic patients. Patients will begin endocrine therapy following the acquisition of week 4 samples (blood and tissue biopsy).

Study Overview

• Status: Withdrawn
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Rosuvastatin

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women with ER+/PR+ HER2-negative breast cancer initiating neoadjuvant endocrine therapy with curative intent OR initiating endocrine therapy for the treatment of metastatic breast cancer with a biopsy accessible primary breast tumor
• The patients may start any FDA approved endocrine therapy (with which they have not been previously treated) at week 4 of the trial except for tamoxifen
• Palbociclib can be started at week 4, if indicated
• Patients with metastatic disease currently on endocrine therapy must be willing to stop endocrine therapy for 2 weeks prior to starting the study and to switch to a new endocrine therapy on the study (at week 4)
• Intact breast tumor present and size measuring at least 1cm at enrollment
• Post-menopausal at enrollment (age ≥ 60, age ≤ 60 and amenorrhea for ≥12 months in the absence of chemotherapy, tamoxifen, ovarian suppression and FSH/estradiol in the post-menopausal range)
• ECOG ≤ 2
• Can be on other endocrine therapy if willing to change a different endocrine therapy agent for the trial
• Must have at least one FDA approved endocrine therapy option with which the patient has not received prior treatment
• Life expectancy > 12 weeks
• Laboratory criteria: normal renal function: creatinine < 1.5 x upper limit of normal (ULN)), liver function: bilirubin < 2 x ULN, transaminases < 2 x ULN and blood counts: WBC ≥ 2.0, Neutrophils ≥1250, platelets ≥50,000, Hemoglobin ≥ 8.
• Age > 18 years
• Patients must have the ability to give informed consent.
• Patients must have a signed informed consent form prior to enrollment on study. -

Exclusion Criteria:

• Statin use in the last 6 months
• Patient has been treated with all FDA approved endocrine therapies or has been treated with all FDA approved endocrine therapies except for tamoxifen (tamoxifen is excluded from the trial)
• Active liver disease with elevated transaminases > 2x ULN
• Known hypersensitivity to rosuvastatin
• Any history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of the cervix) unless the patient has been in remission and off all other cancer therapy for at least 3 years.
• Patients should have no significant psychiatric illness or medical illness that would preclude the ability to comply with the protocol.
• Patients currently taking medications with known rosuvastatin interactions including cyclosporine, gemfibrozil, lopinavir/ritonavir, atazanavir/ritonavir, coumarin anticoagulants, colchicine, fenofibrates, and niacin.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosuvastatin; Two Cohorts, one at 20 mg and one at 40 mg will enroll in a dose escalation of rosuvastatin	Drug: Rosuvastatin; Other Names: Crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety by adverse event	Neoadjuvant - 16 weeks prior to surgery
Maximum tolerated dose	Neoadjuvant - 16 weeks prior to surgery

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in Ki-67 with rosuvastatin alone followed by rosuvastatin in combination with endocrine therapy	12 months after final tumor sample collection
progression free survival	5 years after last subject completion

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Kimberly Blackwell, M.D., Duke University

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2015
• Primary Completion (Actual): May 10, 2017
• Study Completion (Actual): May 10, 2017

Study Registration Dates

• First Submitted: June 25, 2015
• First Submitted That Met QC Criteria: June 25, 2015
• First Posted (Estimate): June 29, 2015

Study Record Updates

• Last Update Posted (Actual): June 5, 2017
• Last Update Submitted That Met QC Criteria: June 2, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Estrogen Receptor Positive
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: Pro00062343

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No