Clinical Trials /

Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer

NCT02046421

Description:

This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and mifepristone when given together with carboplatin in treating patients with breast cancer that is metastatic or cannot be removed by surgery or recurrent or persistent ovarian epithelial, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy, such as carboplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Steroid hormones can cause the growth of cancer cells. Hormone therapy using mifepristone may fight breast and ovarian cancer by lowering the amount of steroid hormone the body makes. Giving carboplatin and gemcitabine hydrochloride together with mifepristone may be an effective treatment for breast, ovarian epithelial, fallopian tube, or primary peritoneal cancer.

Related Conditions:
  • Breast Carcinoma
  • Fallopian Tube Carcinoma
  • Ovarian Carcinoma
  • Primary Peritoneal Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
  • Official Title: Carboplatin, Gemcitabine, and Mifepristone for Advanced Breast Cancer and Recurrent or Persistent Epithelial Ovarian Cancer

Clinical Trial IDs

  • ORG STUDY ID: IRB13-1000
  • SECONDARY ID: NCI-2014-00107
  • SECONDARY ID: IRB13-1000
  • SECONDARY ID: P30CA014599
  • NCT ID: NCT02046421

Conditions

  • Male Breast Cancer
  • Recurrent Breast Cancer
  • Recurrent Fallopian Tube Cancer
  • Recurrent Ovarian Epithelial Cancer
  • Recurrent Primary Peritoneal Cavity Cancer
  • Stage IIIB Breast Cancer
  • Stage IIIC Breast Cancer
  • Stage IV Breast Cancer

Interventions

DrugSynonymsArms
mifepristoneMifegyne, Mifeprex, RU-38486Treatment (mifepristone, carboplatin, gemcitabine)
carboplatinCarboplat, CBDCA, JM-8, Paraplat, ParaplatinTreatment (mifepristone, carboplatin, gemcitabine)
gemcitabine hydrochloridedFdC, difluorodeoxycytidine hydrochloride, gemcitabine, GemzarTreatment (mifepristone, carboplatin, gemcitabine)

Purpose

This phase I trial studies the side effects and best dose of gemcitabine hydrochloride and mifepristone when given together with carboplatin in treating patients with breast cancer that is metastatic or cannot be removed by surgery or recurrent or persistent ovarian epithelial, fallopian tube, or primary peritoneal cancer. Drugs used in chemotherapy, such as carboplatin and gemcitabine hydrochloride, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Steroid hormones can cause the growth of cancer cells. Hormone therapy using mifepristone may fight breast and ovarian cancer by lowering the amount of steroid hormone the body makes. Giving carboplatin and gemcitabine hydrochloride together with mifepristone may be an effective treatment for breast, ovarian epithelial, fallopian tube, or primary peritoneal cancer.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of
      mifepristone when given in combination with carboplatin and gemcitabine (gemcitabine
      hydrochloride).

      SECONDARY OBJECTIVES:

      I. To determine the safety and tolerability of mifepristone in combination with carboplatin
      and gemcitabine.

      II. To describe the toxicities seen with carboplatin, gemcitabine, and mifepristone
      combination therapy.

      TERTIARY OBJECTIVES:

      I. To correlate expression of biomarkers (e.g. glucocorticoid receptor [GR], androgen
      receptor [AR], estrogen receptor [ER], and progesterone receptor [PR]) with treatment
      outcomes.

      II. To correlate serum and intratumoral mifepristone concentrations after two doses of
      mifepristone (in patients with easily accessible tumor who consent to an optional research
      biopsy).

      OUTLINE: This is a dose-escalation study of mifepristone.

      Patients receive mifepristone orally (PO) once daily (QD) on days 0, 1, 7, and 8, and
      carboplatin intravenously (IV) over 30 minutes and gemcitabine hydrochloride IV over 30-60
      minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression
      or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 18 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (mifepristone, carboplatin, gemcitabine)ExperimentalPatients receive mifepristone PO QD on days 0, 1, 7, and 8, and carboplatin IV over 30 minutes and gemcitabine hydrochloride IV over 30-60 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • mifepristone
  • carboplatin
  • gemcitabine hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Patients are eligible if they have the following: metastatic or unresectable breast
             cancer, recurrent or persistent epithelial ovarian, fallopian tube, or primary
             peritoneal cancer

          -  Ovarian cancer patients with both platinum-sensitive and platinum-resistant disease
             are eligible. Ovarian cancer patients with platinum refractory disease (failure to
             achieve a complete response to first line platinum therapy) are ineligible.

          -  Men with metastatic or unresectable breast cancer are eligible

          -  Patients must have measurable or evaluable disease (subjects with elevation of tumor
             marker with no evidence of disease on imaging or exam are not eligible)

          -  Patients with breast cancer may have received neoadjuvant or adjuvant chemotherapy and
             up to two prior chemotherapy regimens for metastatic or locally recurrent disease;
             subjects with ovarian cancer may have had two regimens for advanced or persistent
             disease

          -  Patients with both ER positive and ER negative breast cancer are eligible for this
             study. Patients with HER2 positive disease will be excluded from participation in this
             study.

          -  Metastatic breast cancer patients who are hormone receptor positive at baseline must
             be hormone refractory or have indications for emergent treatment with chemotherapy
             (e.g., visceral crisis).

          -  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 2
             weeks prior to study treatment

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Karnofsky > 60%)

          -  Absolute neutrophil count >= 1,500/mL

          -  Platelets >= 100,000/mL

          -  Total bilirubin =< institutional upper limit of normal (ULN)

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             5 =< X institutional ULN

          -  Creatinine =< institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for
             patients with creatinine levels above institutional normal

          -  Morning cortisol >= institutional normal

          -  If a woman is of childbearing potential, a negative serum or urine pregnancy test is
             required; women of child-bearing potential and men who are sexually active must agree
             to use birth control such as barrier method of birth control, abstinence, or else be
             surgically sterile (tubal ligation, hysterectomy or partner with confirmed vasectomy)
             prior to study entry and for the duration of study participation; hormonal
             contraception is not permitted on trial; alternatively the patient must be
             post-menopausal defined as greater than 12 months without a menstrual cycle; should a
             woman become pregnant or suspect she is pregnant while participating in this study,
             she should inform her treating physician immediately; nursing patients must
             discontinue breast feeding prior to the initiation of therapy

          -  Ability to understand and willingness to sign an informed consent document

          -  Bisphosphonate (e.g. zoledronic acid) and receptor activator of nuclear transcription
             factor kappa-B (NF-kappaB) ligand (RANKL) inhibitor (e.g. denosumab) use for bone
             metastasis is permitted

        Exclusion Criteria:

          -  Patients who have not recovered from toxicities of prior therapy to the point that
             they would be appropriate for re-dosing will be ineligible for study treatment. All
             patients must have a two week washout period from prior chemotherapy.

          -  Patients must be at least two weeks from prior radiation therapy (RT)

          -  Patients must have a one week washout period from prior hormonal therapy (e.g.
             testosterone, estrogen, progestin, gonadotropin-releasing hormone antagonist)

          -  Patients may not be receiving any other investigational agents

          -  Mifepristone inhibits cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
             and induces 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 cytochrome P450, family 2,
             subfamily C, polypeptide 9 (CYP2C9)/cytochrome P450, family 2, subfamily C,
             polypeptide 8 (2C8)

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, poorly controlled hypertension, symptomatic congestive heart failure,
             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
             that would limit compliance with study requirements

          -  Pregnant women are excluded from this study; breastfeeding should be discontinued if
             patient wishes to participate in study

          -  Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
             therapy are ineligible

          -  History of long-term use of corticosteroids or concurrent short-term use of
             corticosteroids is not allowed; short-term corticosteroid use must be discontinued at
             least 2 weeks prior to study treatment

          -  Prior mifepristone use for anticancer therapy is not allowed

          -  Patients with advanced breast cancer who have received platinum therapy (e.g.
             carboplatin or cisplatin) and/or gemcitabine therapy for metastatic disease are
             excluded (platinum-based therapy and/or gemcitabine in the adjuvant or neoadjuvant
             setting is allowed)

          -  Ovarian cancer patients who have received prior gemcitabine therapy are ineligible;
             (prior carboplatin therapy is allowed)

          -  Patients with known grade 2 or greater allergic reactions attributed to compounds of
             similar chemical or biologic composition to mifepristone, carboplatin, or gemcitabine
             are ineligible for study enrollment
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD/RP2D, defined as < 1/6 patients at highest dose level below max administered dose or fewer than 33% of patients experiencing dose limiting toxicity (DLT), graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v) 4.0
Time Frame:21 days
Safety Issue:
Description:Summarized by type and grade overall and for each dose level. Confidence intervals for the proportion of patients experiencing a DLT will be constructed.

Secondary Outcome Measures

Measure:Response to treatment according to Response Evaluation Criteria in Solid Tumors 1.1
Time Frame:Up to 12 weeks
Safety Issue:
Description:
Measure:Progression free survival (PFS)
Time Frame:Up to 18 months
Safety Issue:
Description:Estimated using the method of Kaplan-Meier, and compared between groups using the logrank test. In addition, the association between GR expression status and PFS or overall survival (OS) will be examined using Cox proportional hazards regression with GR status and dose level as covariates.
Measure:OS
Time Frame:Up to 18 months
Safety Issue:
Description:Estimated using the method of Kaplan-Meier, and compared between groups using the logrank test. In addition, the association between GR expression status and PFS or OS will be examined using Cox proportional hazards regression with GR status and dose level as covariates.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:University of Chicago

Last Updated

December 5, 2017