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Abraxane® With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer

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ClinicalTrials.gov Identifier: NCT02788981
Recruitment Status : Recruiting
First Posted : June 2, 2016
Last Update Posted : May 8, 2020
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Tracking Information
First Submitted Date  ICMJE May 25, 2016
First Posted Date  ICMJE June 2, 2016
Last Update Posted Date May 8, 2020
Actual Study Start Date  ICMJE March 28, 2017
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 1, 2016)
Progression-free survival (PFS) [ Time Frame: 12 months ]
Measured using the RECIST guideline v1.1
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 1, 2016)
  • Response rate in glucocorticoid receptor (GR) positivity [ Time Frame: 12 months ]
    Compare the response rate in GR positivity between the placebo and mifepristone groups using the RECIST guideline v1.1
  • Response Rate [ Time Frame: 12 months ]
    Measured using the RECIST guideline v1.1
  • Overall survival [ Time Frame: 24 months ]
    Collected from date of randomization until death
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Abraxane® With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: 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).
    Other Name: KORLYM(R)
  • Other: Placebo
    Patients will receive placebo and nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle).
  • Drug: Nab-Paclitaxel
    Patients will either receive placebo and nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle) or 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). Patients will receive mifepristone and nab-paclitaxel, or placebo and nab-paclitaxel. Not all three.
    Other Name: Abraxane®
Study Arms  ICMJE
  • Experimental: 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)
    Interventions:
    • Drug: Mifepristone
    • Drug: Nab-Paclitaxel
  • Placebo Comparator: Nab-Paclitaxel+Placebo
    Patients will receive placebo and nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle)
    Interventions:
    • Other: Placebo
    • Drug: Nab-Paclitaxel
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 1, 2016)
64
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2024
Estimated Primary Completion Date February 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed breast cancer with stage IV or unresectable stage III disease.
  2. 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).
  3. 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)
  4. 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.
  5. 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.
  6. 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.
  7. Eastern Cooperative Oncology Group performance status ≤ 2 (Karnofsky ≥ 60%).
  8. Patients must have normal organ and marrow function as defined below

    • absolute neutrophil count >1,500 cells/mm3.
    • platelets ≥100,000/mcL
    • hemoglobin > 9.0 g/dL
    • total bilirubin< 1.5 mg/dL
    • alkaline phosphatase < 2.5 X upper limit of normal (ULN) or < 5 X ULN if bone mets are present
    • aspartate aminotransferase (AST) and Alanine transaminase (ALT) < 2.5 ULN or < 5 X ULN if liver mets are present
    • adequate renal function: creatinine ≤ institutional upper limit of normal OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
    • international normalized ratio (INR) < 1.5
  9. Females of child-bearing potential (defined as a sexually mature woman who has not undergone hysterectomy, bilateral oophorectomy, or who has not been naturally postmenopausal for at least 24 consecutive months prior to study enrollment) must:

    • Commit to abstinence from heterosexual contact or agree to use effective contraception without interruption beginning at least 28 days prior to starting protocol therapy and while on study medication.
    • Have a negative serum pregnancy test result at screening and agree to ongoing pregnancy testing during the study dosing
  10. Male subjects must practice true abstinence or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 6 months following protocol discontinuation, even if he has undergone a successful vasectomy.
  11. Patients must have < Grade 2 pre-existing peripheral neuropathy (per CTCAE).
  12. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients who are receiving any other investigational agents.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. Mifepristone can both inhibit CYP3A4 and induce CYP3A4. 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/CYP2C8. 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.

  7. 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.
  8. Pregnant women are excluded from this study because Mifepristone is an abortifacient agent with the potential for teratogenic effects.
  9. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Mifepristone, breastfeeding should be discontinued if the mother wishes to participate in this study.
  10. HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Mifepristone. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
  11. No history of long-term use of corticosteroids or concurrent short term use of corticosteroids is allowed.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Bernadette Libao 773 702 6634 blibao@medicine.bsd.uchicago.edu
Contact: Jackie Peterson 773 834 1746 jdpeterson@medicine.bsd.uchicago.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02788981
Other Study ID Numbers  ICMJE IRB16-0403
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Chicago
Study Sponsor  ICMJE University of Chicago
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Rita Nanda, M.D. University of Chicago
PRS Account University of Chicago
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP