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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Corcept Therapeutics
Sponsor:
Information provided by (Responsible Party):
Corcept Therapeutics
ClinicalTrials.gov Identifier:
NCT02014337
First received: December 4, 2013
Last updated: August 8, 2016
Last verified: August 2016
  Purpose
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

Condition Intervention Phase
Breast Cancer
Ovarian Epithelial Cancer Recurrent
Sarcoma
Non-small Cell Lung Cancer
Carcinoma, Transitional Cell
Prostate Cancer
Prostatic Neoplasms
Drug: Mifepristone and Eribulin in combination
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Corcept Therapeutics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
    In the dose escalation phase: MTD time frame is within 28 days of first dose (Cycle 1)


Estimated Enrollment: 40
Study Start Date: January 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • Korlym®
  • Halaven

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02014337

Locations
United States, Arizona
ACRC/Arizona Clinical Research Center Inc. Recruiting
Tucson, Arizona, United States, 85715
Contact: Manuel Modiano, MD    520-290-2510    admin@acrcresearch.com   
Principal Investigator: Manuel Modiano, MD         
United States, Florida
H. Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Hyo Han, MD    813-745-4933    hyo.han@moffitt.org   
Principal Investigator: Hyo Han, MD         
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30308
Contact: Elisavet Paplomata, MD    404-686-8210    elisavet.paplomata!@emory.edu   
Principal Investigator: Elisavet Paplomata, MD         
United States, Illinois
Rita Nanda, MD Recruiting
Chicago, Illinois, United States, 60637
Contact: Rita Nanda, MD    773-834-2756    rnanda@medicine.bsd.uchicago.edu   
Principal Investigator: Rita Nanda, MD         
United States, Michigan
Quest Research Recruiting
Royal Oaks, Michigan, United States, 48073
Contact: Laura Nadeau, MD    248-288-4500    laura@questri.com   
Principal Investigator: Laura Nadeau, MD         
United States, Missouri
St. Luke's Cancer Institute Recruiting
Kansas City, Missouri, United States, 64111
Contact: Timothy Pluard, MD    816-932-6913    tpluard@saint-lukes.org   
Principal Investigator: Timothy Pluard, MD         
United States, Nevada
Comprehensive Cancer Centers of Nevada Recruiting
Las Vegas, Nevada, United States, 89169
Contact: Fadi Braiteh, MD    702-952-3400    fadi.braiteh@usoncology.com   
Principal Investigator: Fadi Braiteh, MD         
United States, Texas
Texas Oncology-Baylor Charles A. Sammons Cancer Center Recruiting
Dallas, Texas, United States, 75246
Contact: Carlos Becerra, MD    214-370-1179    carlos.becerra@usoncology.com   
Principal Investigator: Carlos Becerra, MD         
Cancer Care Centers of South Texas Recruiting
San Antonio, Texas, United States, 78217
Contact: Sharon Wilks, MD    210-637-0641    sharon.wilks@usoncology.com   
Principal Investigator: Sharon Wilks, MD         
Texas Oncology - Tyler Recruiting
Tyler, Texas, United States, 75702
Contact: Donald Richards, MD    903-579-9800    donald.richards@usoncology.com   
Principal Investigator: Donald Richards, MD         
United States, Virginia
Virginia Cancer Specialists Recruiting
Fairfax, Virginia, United States, 22031
Contact: Neelima Denduluri, MD    703-528-7303    neelima.denduluri@usoncology.com   
Principal Investigator: Neelima Denduluri, MD         
Sponsors and Collaborators
Corcept Therapeutics
Investigators
Principal Investigator: Rita Nanda, MD University of Chicago
  More Information

Responsible Party: Corcept Therapeutics
ClinicalTrials.gov Identifier: NCT02014337     History of Changes
Other Study ID Numbers: C1073-500 
Study First Received: December 4, 2013
Last Updated: August 8, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Corcept Therapeutics:
Mifepristone
Eribulin Mesylate
Breast Cancer
Ovarian Cancer
Sarcoma
Non-small cell lung cancer
Carcinoma, transitional cell
Prostate cancer
Prostatic neoplasms

Additional relevant MeSH terms:
Breast Neoplasms
Prostatic Neoplasms
Carcinoma, Non-Small-Cell Lung
Sarcoma
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Triple Negative Breast Neoplasms
Carcinoma, Transitional Cell
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Genital Neoplasms, Male
Urogenital Neoplasms
Genital Diseases, Male
Prostatic Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female

ClinicalTrials.gov processed this record on December 09, 2016