RATIONALE: Drugs used in chemotherapy, such as cisplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving more than one drug (combination chemotherapy) together with everolimus may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of cisplatin, paclitaxel, and everolimus when given together for the treatment of patients with metastatic breast cancer.
OBJECTIVES: Primary * To establish the safety profile and the maximum tolerated dose of the combination of cisplatin, paclitaxel, and everolimus in patients with metastatic breast cancer. Secondary * To explore the antitumor activity of this regimen, in terms of response rate and time to progression in these patients. OUTLINE: This is a multicenter study. Patients receive cisplatin intravenously (IV) over 1 hour and paclitaxel IV over 1 hour on days 1, 8, and 15. Patients receive oral everolimus on days 1, 8, 15, and 21. Courses repeat every 4 weeks in the absence of disease progression and unaccepted toxicity. After completion of study therapy, patients are followed at 4 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
* Dose Level: -3 20mg/m2/week 3-6 patients * Dose Level: -2 20mg/m2/week 3-6 patients * Dose Level: -1 25mg/m2/week 3-6 patients * Dose Level: 1 25mg/m2/week 3-6 patients * Dose Level: 2 25mg/m2/week 3-6 patients * Dose Level: 3 25mg/m2/week 3-6 patients
* Dose Level: -3 20mg/m2/week 3-6 patients * Dose Level: -2 20mg/m2/week 3-6 patients * Dose Level: -1 20mg/m2/week 3-6 patients * Dose Level: 1 20mg/m2/week 3-6 patients * Dose Level: 2 25mg/m2/week 3-6 patients * Dose Level: 3 30mg/m2/week 3-6 patients
* Dose Level: -3 65mg/m2/week 3-6 patients * Dose Level: -2 70mg/m2/week 3-6 patients * Dose Level: -1 70mg/m2/week 3-6 patients * Dose Level: 1 80mg/m2/week 3-6 patients * Dose Level: 2 80mg/m2/week 3-6 patients * Dose Level: 3 80mg/m2/week 3-6 patients
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, United States
Sarah Cannon Cancer Center at Centennial Medical Center
Nashville, Tennessee, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States
Safety profile and maximum tolerated dose
The Maximum Tolerated Dose (MTD) will be the dose level at which fewer than 2 of 6 (or 33% of) patients experience dose limiting toxicity (DLT).
Time frame: At 4 weeks
Antitumor activity
Cisplatin + Paclitaxel + RAD001 combination by determining response rates (RR) and time to progression (TTP) achieved with treatment
Time frame: Date of study entry to date of progression of disease
Response rate
Time frame: at baseline and every 8 weeks to disease progression
Time to progression
Time frame: date of study entry to date of disease progression
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