Clinical Trials /

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

NCT02483871

Description:

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).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Withdrawn

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Dose Optimization of Rosuvastatin in Early Stage and Metastatic Estrogen Receptor Positive Breast Cancer Patients on Endocrine Therapy
  • Official Title:

Clinical Trial IDs

  • ORG STUDY ID: Pro00062343
  • NCT ID: NCT02483871

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
RosuvastatinCrestorRosuvastatin

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
RosuvastatinExperimentalTwo Cohorts, one at 20 mg and one at 40 mg will enroll in a dose escalation of rosuvastatin
  • Rosuvastatin

Eligibility Criteria

        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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety by adverse event
Time Frame:Neoadjuvant - 16 weeks prior to surgery
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Withdrawn
Lead Sponsor:Duke University

Trial Keywords

  • Estrogen Receptor Positive

Last Updated

June 2, 2017