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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02483871
Recruitment Status : Withdrawn (Enrollment did not meet anticipated goals. Eligibility was a challenge.)
First Posted : June 29, 2015
Last Update Posted : June 5, 2017
Information provided by (Responsible Party):
Duke University

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Rosuvastatin Phase 1

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Actual Study Start Date : October 2015
Actual Primary Completion Date : May 10, 2017
Actual Study Completion Date : May 10, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

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 Name: Crestor

Primary Outcome Measures :
  1. Safety by adverse event [ Time Frame: Neoadjuvant - 16 weeks prior to surgery ]
  2. Maximum tolerated dose [ Time Frame: Neoadjuvant - 16 weeks prior to surgery ]

Secondary Outcome Measures :
  1. Change in Ki-67 with rosuvastatin alone followed by rosuvastatin in combination with endocrine therapy [ Time Frame: 12 months after final tumor sample collection ]
  2. progression free survival [ Time Frame: 5 years after last subject completion ]

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02483871

United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Principal Investigator: Kimberly Blackwell, M.D. Duke University

Responsible Party: Duke University Identifier: NCT02483871     History of Changes
Other Study ID Numbers: Pro00062343
First Posted: June 29, 2015    Key Record Dates
Last Update Posted: June 5, 2017
Last Verified: June 2017

Keywords provided by Duke University:
Estrogen Receptor Positive

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Rosuvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs