A Randomized, Placebo-Controlled, Double-Blind, Phase II Trial of Nanoparticle Albumin-Bound Paclitaxel (Nab-Paclitaxel, Abraxane®) With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer

University of Chicago5 sites in 1 country29 target enrollmentMarch 28, 2017

ConditionsBreast Cancer

InterventionsMifepristone Nab-Paclitaxel Placebo

DrugsMifepristone Nab-Paclitaxel

Overview

Phase: Phase 2
Intervention: Mifepristone
Conditions: Breast Cancer
Sponsor: University of Chicago
Enrollment: 29
Locations: 5
Primary Endpoint: Progression-free Survival (PFS)
Status: Active, not recruiting
Last Updated: 10 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a randomized, placebo-controlled, double-blind, phase II trial of nab-paclitaxel with or without mifepristone for advanced, glucocorticoid receptor-positive, triple-negative breast cancer. A total of 64 patients will receive nab-paclitaxel. Patients will be randomly assigned to either receive placebo or to receive mifepristone daily on the day prior to and day of each dose of nab-paclitaxel. Patients will be enrolled over 12 months and followed for 12 months following completion of study.

To expand and follow up on the investigators understanding of a potential pharmacokinetic (PK) interaction between nab-paclitaxel and mifepristone, investigators will perform PK studies in the first 20 patients enrolled at pre-specified "PK sites".

Detailed Description

Primary Objective: To compare the progression free survival (PFS) of patients treated with nab-paclitaxel + placebo and patients treated with nab-paclitaxel + mifepristone. Secondary Objectives: 1. To correlate percentage glucocorticoid receptor (GR) positivity in the most recent metastatic tumor biopsy (or in primary tumor if only primary tumor is available) with PFS in mifepristone and placebo groups. 2. To perform an exploratory assessment of overall response rate in both groups. 3. To collect information regarding overall survival in both treatment cohorts.

Registry

clinicaltrials.gov

Start Date

March 28, 2017

End Date

August 2026

Last Updated

10 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University of Chicago

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Patients must have histologically or cytologically confirmed breast cancer with stage IV or unresectable stage III disease.
•Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, MRI, or calipers by clinical exam. To be considered pathologically enlarged and measurable, a lymph node must be ≥15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm).
•Triple-negative breast cancer (defined as estrogen receptor (ER) and progesterone receptor (PR) \<10% positive; HER2 0-1+ by immuno-histochemistry (IHC) or fluorescence in situ hybridization (FISH) ratio \<2.0)
•Patients must have tumor block or slides available for testing, and tumor must be glucocorticoid receptor positive (defined as GR \>10% moderate to strong staining by central lab). A formalin-fixed, paraffin-embedded surgical or core needle biopsy obtained from the primary tumor or from a metastasis and containing viable tumor tissue is required for this evaluation. Fine needle aspirates or other alternative cytology samples are not acceptable.
•Patients may have received adjuvant chemotherapy and up to two prior chemotherapy for metastatic or locally recurrent disease. No prior nab-paclitaxel or mifepristone therapy for metastatic disease will be allowed.
•Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of Nab-Paclitaxel in combination with Mifepristone in patients \< 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
•Eastern Cooperative Oncology Group performance status ≤ 2 (Karnofsky ≥ 60%).
•Patients must have normal organ and marrow function as defined below
•absolute neutrophil count \>1,500 cells/mm
•platelets ≥100,000/mcL

Exclusion Criteria

•Patients who are receiving any other investigational agents.
•Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
•Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.
•Patients with known brain metastases will be eligible as long as they have completed radiation to the brain, and have been off of corticosteroid therapy for at least 7 days.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to mifepristone or paclitaxel/nab-paclitaxel. Patients with a history of mild infusion reactions with paclitaxel who were able to continue to receive paclitaxel with corticosteroid premedication will be eligible to participate, as these cases were likely related to cremaphor and not paclitaxel.
•Mifepristone can both inhibit CYP3A4 and induce CYP3A
•Addition of mifepristone to a pre-existing drug regimen may cause a mild and temporary increase in plasma drug concentration of drugs with significant CYP3A4 metabolism. Medications that are strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's Wort may decrease plasma mifepristone levels. Strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma mifepristone concentrations.
•Mifepristone may increase the plasma drug concentration of concomitant medications with metabolism mediated by CYP2C9/CYP2C
•Drugs with the largest increases will be those whose metabolism is largely or solely mediated by CYP2C9/2C8 and include: Non-steroidal Anti-inflammatory drugs (NSAIDs) and warfarin.
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Arms & Interventions

Nab-Paclitaxel+Mifepristone

Patients will receive mifepristone 300 mg daily on the day prior to and day of each dose of nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle)

Intervention: Mifepristone

Nab-Paclitaxel+Mifepristone

Patients will receive mifepristone 300 mg daily on the day prior to and day of each dose of nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle)

Intervention: Nab-Paclitaxel