Carboplatin, Gemcitabine Hydrochloride, and Mifepristone in Treating Patients With Advanced Breast Cancer or Recurrent or Persistent Ovarian Epithelial, Fallopian Tube, or Primary Peritoneal Cancer
|ClinicalTrials.gov Identifier: NCT02046421|
Recruitment Status : Active, not recruiting
First Posted : January 27, 2014
Last Update Posted : December 7, 2017
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: mifepristone Drug: carboplatin Drug: gemcitabine hydrochloride Other: laboratory biomarker analysis Other: pharmacological study||Phase 1|
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).
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.
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 (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Carboplatin, Gemcitabine, and Mifepristone for Advanced Breast Cancer and Recurrent or Persistent Epithelial Ovarian Cancer|
|Actual Study Start Date :||November 2013|
|Estimated Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||June 2018|
Experimental: Treatment (mifepristone, carboplatin, gemcitabine)
Patients 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.
Drug: gemcitabine hydrochloride
Other: laboratory biomarker analysis
Other: pharmacological study
Other Name: pharmacological studies
- 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 ]Summarized by type and grade overall and for each dose level. Confidence intervals for the proportion of patients experiencing a DLT will be constructed.
- Response to treatment according to Response Evaluation Criteria in Solid Tumors 1.1 [ Time Frame: Up to 12 weeks ]
- Progression free survival (PFS) [ Time Frame: Up to 18 months ]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.
- OS [ Time Frame: Up to 18 months ]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.
- GR expression [ Time Frame: Up to 18 months ]The association between GR expression and treatment response will be examined descriptively. Immunohistochemical detection of GR will be scored and dichotomized as described by Belova et al. Examined using Cox proportional hazards regression with GR status and dose level as covariates.
- Presence or evolution/change of ER between primary and metastatic tumor [ Time Frame: Up to 18 months ]
- Presence or evolution/change of PR between primary and metastatic tumor [ Time Frame: Up to 18 months ]
- Presence or evolution/change of AR between primary and metastatic tumor [ Time Frame: Up to 18 months ]
- Mean tumor shrinkage [ Time Frame: Day 2 ]Tumor shrinkage will be compared between groups using the Wilcoxon rank-sum test.
- Proportion of responders in GR+ and GR- groups [ Time Frame: Day 2 ]Response rates will be compared using the Fisher's exact test.
- Mifepristone tumor levels [ Time Frame: Day 1 of course 1 (just prior to 2nd mifepristone dose administration) and day 8 of course 1 (just prior to 4th mifepristone dose administration) ]The relationship between blood and biopsy concentrations will be summarized using the correlation coefficient; a linear regression model may also be used depending on the number of available biopsies.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02046421
|United States, Illinois|
|University of Chicago Comprehensive Cancer Center|
|Chicago, Illinois, United States, 60637-1470|
|NorthShore University HealthSystem|
|Evanston, Illinois, United States, 60201|
|Principal Investigator:||Rita Nanda||University of Chicago Comprehensive Cancer Center|