Clinical Trials /

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

NCT02014337

Description:

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

Related Conditions:
  • Bladder Carcinoma
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Non-Small Cell Lung Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
  • Prostate Carcinoma
  • Sarcoma
  • Urothelial Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Mifepristone and Eribulin in Patients With Metastatic Triple Negative Breast Cancer or Other Specified Solid Tumors
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: C1073-500
  • NCT ID: NCT02014337

Conditions

  • Breast Cancer
  • Ovarian Epithelial Cancer Recurrent
  • Sarcoma
  • Non-small Cell Lung Cancer
  • Carcinoma, Transitional Cell
  • Prostate Cancer
  • Prostatic Neoplasms

Interventions

DrugSynonymsArms
Mifepristone and Eribulin in combinationKorlym®, HalavenMifepristone and Eribulin in combination

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
Mifepristone and Eribulin in combinationExperimentalSingle Arm
  • Mifepristone and Eribulin in combination

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:In the dose escalation phase: MTD time frame is within 28 days of first dose (Cycle 1)

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Corcept Therapeutics

Trial Keywords

  • Mifepristone
  • Eribulin Mesylate
  • Breast Cancer
  • Ovarian Cancer
  • Sarcoma
  • Non-small cell lung cancer
  • Carcinoma, transitional cell
  • Prostate cancer
  • Prostatic neoplasms

Last Updated

January 12, 2018