Mifepristone and Eribulin in Patients With Metastatic Triple Negative Breast Cancer or Other Specified Solid Tumors

January 12, 2018 updated by: Corcept Therapeutics

Phase 1 Study of Mifepristone in Combination With Eribulin in Patients With Locally Advanced/Metastatic Breast or Other Specified Solid Tumors, With a Dose Expansion Cohort in Patients With Triple Negative Breast Cancer.

This is a study to assess the safety of the combination of mifepristone and eribulin in patients with metastatic or locally advanced unresectable breast or other specified solid tumors, and determine preliminary efficacy of the combination of mifepristone and eribulin in patients with metastatic or locally advanced unresectable Triple Negative Breast Cancer (TNBC). The structure for the study is a single arm, non-randomized, open-label, multicenter trial with no control group. The study will be conducted at up to 11 sites, with up to 40 evaluable patients

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

There will be two parts to the study: Part 1, a dose escalation phase, in which the MTD and RP2D will be determined in up to 20 patients with metastatic breast or other specified solid tumors, regardless of receptor status; and Part 2, a dose expansion phase in which a preliminary estimate of efficacy will be made in an expansion group of up to 20 patients with glucocorticoid receptor-positive metastatic TNBC at the RP2D.

Treatment will be administered in 21-day cycles, with the exception of the first cycle, which will be of 28 days duration with a lead-in of 7 days dosing of mifepristone.

Cycle 1 (28-day cycle): Mifepristone administered orally (PO) with food once daily for 28 days. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on days 8 and 15.

Cycle 2 and beyond (21-day cycle): Mifepristone administered orally (PO) with food once daily for 21 days. Eribulin will be administered intravenously (IV) over 2 to 5 minutes on days 1 and 8.

Enrollment in Part 2 of the study (dose expansion) will occur once the RP2D has been determined. Patients in the dose expansion study must have TNBC disease that is glucocorticoid receptor-positive (by immunohistochemistry [IHC]). Patients will be treated in repeated 21-day cycles until progression or another withdrawal criterion is met.

Part 1 of the study is complete. Part 2 of the study is ongoing.

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85715
        • ACRC/Arizona Clinical Research Center Inc.
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center & Research Institute
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Winship Cancer Institute, Emory University
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Rita Nanda, MD
    • Michigan
      • Royal Oaks, Michigan, United States, 48073
        • Quest Research
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • St. Luke's Cancer Institute
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology-Baylor Charles A. Sammons Cancer Center
      • San Antonio, Texas, United States, 78217
        • Cancer Care Centers of South Texas
      • Tyler, Texas, United States, 75702
        • Texas Oncology - Tyler
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Informed consent given prior to study-specific screening procedures
  2. ≥ 18 years old

Part 2, dose expansion:

  1. Diagnosis of TNBC: < 1% cells positive for ER/progesterone receptor, and HER2 IHC score of 0 or 1, or FISH HER2+ ratio of less than 1.8; patients with low ER IHC (> 1% but < 10% cells positive), but negative by genomic assay are eligible
  2. Inoperable metastatic or locally advanced unresectable disease
  3. Patients should have received a minimum of one, and up to five prior chemotherapy regimens
  4. Must have submitted a diagnostic FFPE tumor tissue sample to confirm tumor GR positivity. Tumor tissue may be from primary or metastatic lesion. In the absence of sufficient tissue to complete IHC, a tumor biopsy will be required.
  5. Tumor must be glucocorticoid receptor positive TNBC (≥10% positive cells by IHC of tumor biopsy)
  6. Must have measurable disease (RECIST v1.1) in at least one lesion not previously irradiated unless documented evidence of progression
  7. Patients with treated, stable brain metastases eligible providing treatment was ≥4 weeks prior to initiation of study drug, and baseline CT or MRI negative for new brain metastases. Must not require therapy with corticosteroids.
  8. ECOG performance status 0 or 1

  9. Must have adequate bone marrow and renal/hepatic function at the screening visit (≤7 days preceding the lab assessment):

    i. ANC ≥ 1,500/mm3, without G-CSF

    ii. Platelets ≥ 100,000/mm3, without transfusion

    iii. Hemoglobin ≥ 9 g/dL, without transfusion support

    iv. AST or ALT ≤ 3 × ULN

    v. Total serum bilirubin ≤ 1.5 times ULN

    vi. Serum creatinine ≤ ULN

    vii. Potassium and magnesium levels within normal limits. If below the lower limit of normal, must have levels corrected by supplementation prior to starting study drug.

    viii. albumin > 3.0 g/dL

  10. PT/aPIT ≤ 1.5 x ULN
  11. Disease-free period of > 3 years from any other previous malignancies, excluding curatively treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
  12. Female patients of childbearing potential must have a negative serum pregnancy test. Sexually active patients must be willing to use non-hormonal contraception, including condom use by male partner, and barrier method by the female partner during the treatment period and for at least 3 months after the last dose of the study drug. Females considered not of childbearing potential include those who have been in menopause > 2 years, or are surgically sterile (status post tubal ligation or hysterectomy).
  13. Must be able and willing to comply with the study visit schedule and study procedures.
  14. Able to take oral medications

Exclusion Criteria:

  1. Systemic cytotoxic therapies or radiotherapy ≤14 days prior to day 1 cycle 1
  2. Major surgery within 4 weeks, or minor surgery within 2 weeks prior to day 1 of cycle 1
  3. Endometrial bleeding
  4. For two weeks prior to day 1 cycle 1, administration of specified cytochrome P450 3A (CYP3A) inducers
  5. Patients who are taking simvastatin or lovastatin. Patients should be switched to alternative therapies a minimum of 2 weeks before starting study drug
  6. Patients who have been treated with an investigational agent <21 days prior to day 1 of cycle 1
  7. Concomitant use of biological agents including growth factors. Exception: 3- to 6-patient breast cancer cohort enrolled to explore the use of prophylactic growth-factor support of a 1.4 mg/m2 dose of eribulin.
  8. Patients who require treatment with systemic corticosteroids for serious medical conditions or illnesses (e.g. immunosuppression after organ transplantation)
  9. History of significant cardiac disease. Includes second/third degree heart block; significant ischemic heart disease; mean QTc interval > 480 msec prior to study start; poorly controlled hypertension; congestive heart failure of NYHA Class II or worse
  10. Pregnant or breast-feeding
  11. Any other significant co-morbid conditions that would impair study participation or cooperation
  12. In Part 2, unable or unwilling to consent to provision of tumor tissue for GR assay

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Mifepristone and Eribulin in combination
Single Arm
Drug: Mifepristone and Eribulin in combination
Single Arm, Two Parts Part 1: Dose Escalation Phase to determine MTD and RP2D in up to 20 patients Part 2: Dose Expansion Phase at RP2D in 20 patients
Other Names:
  • Halaven
  • Korlym®

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine the MTD and recommended Phase 2 dose (RP2D) of the combination of mifepristone and eribulin in patients with metastatic or locally advanced unresectable breast or other specified solid tumors.
Time Frame: 28 days
In the dose escalation phase: MTD time frame is within 28 days of first dose (Cycle 1)
28 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Corcept Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2014

Primary Completion (ACTUAL)

December 1, 2017

Study Completion (ACTUAL)

December 1, 2017

Study Registration Dates

First Submitted

December 4, 2013

First Submitted That Met QC Criteria

December 12, 2013

First Posted (ESTIMATE)

December 18, 2013

Study Record Updates

Last Update Posted (ACTUAL)

January 17, 2018

Last Update Submitted That Met QC Criteria

January 12, 2018

Last Verified

January 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C1073-500

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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