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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, United States
NorthShore University HealthSystem
Evanston, Illinois, United States
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
Summarized by type and grade overall and for each dose level. Confidence intervals for the proportion of patients experiencing a DLT will be constructed.
Time frame: 21 days
Response to treatment according to Response Evaluation Criteria in Solid Tumors 1.1
Time frame: Up to 12 weeks
Progression free survival (PFS)
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.
Time frame: Up to 18 months
OS
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.
Time frame: Up to 18 months
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