Eribulin Mesylate and Everolimus in Treating Patients With Triple-Negative Metastatic Breast Cancer
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|ClinicalTrials.gov Identifier: NCT02120469|
Recruitment Status : Recruiting
First Posted : April 22, 2014
Last Update Posted : December 15, 2017
|Condition or disease||Intervention/treatment||Phase|
|Estrogen Receptor Negative HER2/Neu Negative Progesterone Receptor-negative Stage IV Breast Cancer Triple-negative Breast Carcinoma||Drug: everolimus Drug: eribulin mesylate Other: pharmacological study Other: laboratory biomarker analysis||Phase 1|
I. To determine the safety and tolerability of everolimus and eribulin (eribulin mesylate), and determine the recommended Phase IB dose (RP2D) of the drug combination in patients with resistant metastatic triple negative breast cancer (TNBC). (Phase I) II. To evaluate the event-free survival (EFS) rate for patients with resistant metastatic TNBC at the RP2D of everolimus and eribulin to determine if the drug combination is worthy of further study. (Phase IB)
I. To determine response rate in patients with resistant metastatic TNBC. (Phase IB) II. To determine overall survival (OS) in patients with resistant metastatic TNBC. (Phase IB) III. To determine toxicity in patients with resistant metastatic TNBC. (Phase IB) IV. To determine pharmacokinetics (PK) for everolimus and eribulin in patients with resistant metastatic TNBC. (Phase IB) V. To collect blood, skin punch biopsies, and tumor biopsies before and after treatment from all patients and perform proteomic analysis to determine the level of inhibition of the phosphatidylinositol 3 kinase (PI3K) pathway in tumor cells versus non-therapeutic targets. (Phase IB)
OUTLINE: This is a dose-escalation study of everolimus.
Patients receive everolimus orally (PO) once daily (QD) on days 1-21 and eribulin mesylate intravenously (IV) 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 for 21 days and then periodically.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I/IB Trial of Eribulin and Everolimus in Patients With Triple Negative Metastatic Breast Cancer|
|Study Start Date :||October 1, 2014|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2018|
Experimental: Treatment (everolimus, eribulin mesylate)
Patients receive everolimus PO QD on days 1-21 and eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Other Names:Drug: eribulin mesylate
Other Names:Other: pharmacological study
Other Name: pharmacological studiesOther: laboratory biomarker analysis
Optional correlative studies
- Dose limiting toxicity (DLT) defined as an adverse event (AE) or abnormal laboratory value as at least possibly related to the study medication and meets any of the criteria per NCI CTCAE v4.0 (Phase I) [ Time Frame: 21 days ]Tables will be created to summarize all toxicities and side effects by dose, course, organ and severity. Rates and associated 95% confidence limits will be estimated for dose-limiting toxicities at the RP2D.
- Event-free survival using the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Phase IB) [ Time Frame: At 4 months ]Rates and associated 95% confidence limits will be estimated.
- Incidence of adverse events, graded according to the NCI CTCAE v4.0 (Phase IB) [ Time Frame: Up to 2 years ]Tables will be created to summarize all toxicities and side effects by dose, course, organ and severity. Rates and associated 95% confidence limits will be estimated.
- Response rate using the RECIST (Phase IB) [ Time Frame: Up to 2 years ]Rates and associated 95% confidence limits will be estimated.
- Overall survival (Phase IB) [ Time Frame: Up to 2 years ]Kaplan Meier methods will be used to estimate the median and 95% confidence limits.
- PK parameters of everolimus in blood samples (Phase Ib) [ Time Frame: Baseline, 1, 2, 4, 6, and 24 hours on day 1 of course 1 and 2 ]Non-compartmental PK analyses of everolimus will be performed using statistical moment theory and according to the rule of linear trapezoids and statistical moment theory. Everolimus PK parameters (maximum concentration, trough concentration, area under the curve [AUC], oral clearance, and half-life) will be determined for each individual and a two-stage approach will be used to describe the study population PK. Descriptive statistics will be provided for the PK parameters.
- PK parameters of eribulin mesylate in plasma samples (Phase Ib) [ Time Frame: Baseline, 5, 10, 15, and 30 minutes, 1, 2, 4, 6, 24, 48, 72, and 167 hours on day 1 of course 2 ]Compartmental analyses will be performed for eribulin mesylate data. Secondary pharmacokinetic parameters (e.g. CLsys, Volume of distribution [Vd], half-life [t1/2], and area under the curve [AUC 0->infinity) will be determined for each individual and a two-stage approach will be used to describe the study population pharmacokinetics. Population means and standard deviations will be compared to values obtained from patients treated on trials of single agent eribulin mesylate.
- Progression free survival (Phase Ib) [ Time Frame: Up to 2 years ]Kaplan Meier methods will be used to estimate the median and 95% confidence limits.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02120469
|United States, California|
|City of Hope Medical Center||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Yuan Yuan, MD, PhD 626-256-4673 YYuan@coh.org|
|Principal Investigator: Yuan Yuan, MD, PhD|
|City of Hope Rancho Cucamonga||Recruiting|
|Rancho Cucamonga, California, United States, 91730|
|Contact: Valerie Estala 626-256-4673 ext 81699|
|Sub-Investigator: Behnam Ebrahimi, MD|
|South Pasadena Cancer Center||Recruiting|
|South Pasadena, California, United States, 91030|
|Contact: Odessa Rodriguez 626-256-4673 ext 81409|
|Sub-Investigator: Christina Yeon, MD|
|Principal Investigator:||Yuan Yuan, MD, PhD||City of Hope Medical Center|