A Phase I Study of Cisplatin, Paclitaxel, and RAD001 Patients With Metastatic Breast Cancer
Overview
- Phase
- Phase 1
- Intervention
- cisplatin
- Conditions
- Breast Cancer
- Sponsor
- Vanderbilt-Ingram Cancer Center
- Enrollment
- 18
- Locations
- 4
- Primary Endpoint
- Safety profile and maximum tolerated dose
- Status
- Completed
- Last Updated
- 13 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Ingrid Mayer, MD
Assistant Professor of Medicine; Clinical Director, Breast Cancer Program; Medical Oncologist
Vanderbilt-Ingram Cancer Center
Eligibility Criteria
Inclusion Criteria
- •DISEASE CHARACTERISTICS:
- •Histologically confirmed invasive mammary carcinoma
- •Stage IV disease
- •No locally recurrent breast cancer
- •Patients with HER2/neu overexpressing tumors must have received prior trastuzumab (Herceptin®) in first-line treatment of metastatic breast cancer
- •Patients with estrogen receptor- or progesterone receptor-expressing tumors must have received prior endocrine therapy (i.e., aromatase inhibitors, fulvestrant, tamoxifen, or ovarian ablation) in first-line treatment of metastatic breast cancer
- •No symptomatic brain metastases
- •Patients with a history of brain metastases must be clinically stable and not taking steroids or therapeutic anticonvulsants that are CYP3A4 modifiers
- •Patients with asymptomatic brain metastases on prophylactic convulsants that are CYP3A4 modifiers are not eligible
- •Hormone receptor status not specified
Exclusion Criteria
- •PRIOR CONCURRENT THERAPY:
- •See Disease Characteristics
- •Recovered from all prior treatment
- •Must not have exceeded a total cumulative dose of life-time exposure of doxorubicin hydrochloride ≤ 360 mg/m² or epirubicin hydrochloride ≤ 640 mg/m²
- •At least 2 weeks since other prior investigational drugs
- •No prior resection of the stomach or small bowel
- •No more than 4 prior chemotherapy regimens in the metastatic setting
- •This restriction does not include endocrine therapies or single agent biologic therapies (i.e., trastuzumab)
- •Concurrent radiotherapy to painful bone metastases or areas of impending bone fracture allowed as long as radiotherapy is initiated prior to study entry
- •No concurrent trastuzumab
Arms & Interventions
Therapeutic Intervention
Intervention: cisplatin
Therapeutic Intervention
Intervention: everolimus
Therapeutic Intervention
Intervention: paclitaxel
Outcomes
Primary Outcomes
Safety profile and maximum tolerated dose
Time Frame: At 4 weeks
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).
Secondary Outcomes
- Antitumor activity(Date of study entry to date of progression of disease)
- Response rate(at baseline and every 8 weeks to disease progression)
- Time to progression(date of study entry to date of disease progression)