Clinical Trials /

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

NCT02788981

Description:

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".

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

A Trial of Nanoparticle <span class="go-doc-concept go-doc-intervention">Albumin-Bound Paclitaxel</span> (<span class="go-doc-concept go-doc-intervention">Nab-Paclitaxel</span>, <span class="go-doc-concept go-doc-intervention">Abraxane</span>) With or Without <span class="go-doc-concept go-doc-intervention">Mifepristone</span> for Advanced, <span class="go-doc-concept go-doc-alteration">Glucocorticoid Receptor-Positive</span>, <span class="go-doc-concept go-doc-alteration">Triple-Negative Breast Cancer</span>

Title

  • Brief Title: A Trial of Nanoparticle Albumin-Bound Paclitaxel (Nab-Paclitaxel, Abraxane) With or Without Mifepristone for Advanced, Glucocorticoid Receptor-Positive, Triple-Negative Breast Cancer
  • Official Title: 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
  • Clinical Trial IDs

    NCT ID: NCT02788981

    ORG ID: IRB16-0403

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Mifepristone Nab-Paclitaxel+Mifepristone
    Nab-Paclitaxel Abraxane Nab-Paclitaxel+Mifepristone, Nab-Paclitaxel+Placebo

    Trial Purpose

    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 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.

    Trial Arms

    Name Type Description Interventions
    Nab-Paclitaxel+Mifepristone Experimental 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) Mifepristone, Nab-Paclitaxel
    Nab-Paclitaxel+Placebo Placebo Comparator Patients will receive placebo and nab-paclitaxel (100 mg/m2 on days 1, 8 and 15 of each 28 day cycle) Nab-Paclitaxel

    Eligibility Criteria

    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 ER and PR <10% positive; HER2 0-1+ by IHC
    or 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. ECOG performance status 2 (Karnofsky 60%, see Appendix A).

    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 ULN or < 5 X ULN if bone mets are present

    - AST and 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.

    - 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, while on study medication, and for 6 months following the last
    dose of therapy.

    - Have a negative serum pregnancy test result at screening.

    10. Male subjects must practice 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.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Progression-free survival (PFS)

    Secondary Outcome Measures

    Response rate in glucocorticoid receptor (GR) positivity

    Response Rate

    Overall survival

    Trial Keywords

    triple-negative breast cancer

    advanced breast cancer

    nab-paclitaxel

    mifepristone

    glucocorticoid receptor-positive breast cancer