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

NCT02483871 | Withdrawn Phase 1

• 1 other identifier: Pro00062343
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Breast Cancer

Keywords

Estrogen Receptor Positive

Outcome Measures

Primary Outcomes (2)

• Safety by adverse event

  Neoadjuvant - 16 weeks prior to surgery

• Maximum tolerated dose

  Neoadjuvant - 16 weeks prior to surgery

Secondary Outcomes (2)

• 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

Study Arms (1)

Rosuvastatin

EXPERIMENTAL

Two Cohorts, one at 20 mg and one at 40 mg will enroll in a dose escalation of rosuvastatin

Drug: Rosuvastatin

Interventions

Rosuvastatin DRUG

Also known as: Crestor

Rosuvastatin

Eligibility Criteria

• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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. -

You may not qualify if:

• 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.

Sponsors & Collaborators

• Duke University: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Rosuvastatin Calcium

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Fluorobenzenes; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kimberly Blackwell, M.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: June 29, 2015
• Study Start: October 1, 2015
• Primary Completion: May 10, 2017
• Study Completion: May 10, 2017
• Last Updated: June 5, 2017

Record last verified: 2017-06

Locations

US (1)