Cisplatin and Everolimus in Treating Patients With Advanced Solid Tumors
- Conditions
- Unspecified Adult Solid Tumor, Protocol Specific
- Interventions
- Genetic: gene expression analysisOther: immunohistochemistry staining methodOther: laboratory biomarker analysisOther: pharmacological studyProcedure: biopsy
- Registration Number
- NCT00423865
- Lead Sponsor
- Memorial Sloan Kettering Cancer Center
- Brief Summary
RATIONALE: Drugs used in chemotherapy, such as cisplatin, 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. Everolimus may also help cisplatin work better by making tumor cells more sensitive to the drug. Giving cisplatin together with everolimus may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of everolimus when given together with cisplatin in treating patients with advanced solid tumors or recurrent or metastatic solid tumors.
- Detailed Description
OBJECTIVES:
Primary
* Determine the recommended phase II dose of everolimus when administered with low-dose cisplatin in patients with advanced solid tumors.
Secondary
* Determine the safety and tolerability of this regimen in these patients.
* Describe the pharmacokinetics of this regimen in patients with advanced solid tumors.
* Assess the effects of this regimen on p53 and p21 immunohistochemistry assays of pre- and post-treatment tumor biopsies from patients with recurrent or metastatic solid tumors.
OUTLINE: This is a dose-escalation study of everolimus (part A) followed by a biological marker study (part B).
* Part A (closed to accrual as of 1/2009): Patients receive cisplatin\* IV over 30 minutes on days 1, 8, and 15 and oral everolimus\* once daily on days 1-21. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of everolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose proceeding that at which 2 of 6 patients experience dose-limiting toxicity (DLT) during course 1. The recommended phase II dose is defined as the dose at which 1 of 6 patients experience DLT during course 1.
Blood is drawn periodically on days 1 and 8 of course 1 for pharmacokinetic studies.
* NOTE: \*Patients who have completed 5 courses of treatment and maintain stable disease or better may continue treatment with everolimus alone or in combination with cisplatin
* Part B: Patients undergo biopsy of the primary tumor, metastatic deposit, or involved lymph node. No more than 14 days later, patients receive everolimus at the recommended phase II dose and cisplatin as in part A.
Patients undergo another tumor biopsy on day 15 of course 1, before receiving chemotherapy. The pre- and post-therapy tissue is examined by immunochemistry and analyzed for p53 and p21 expression.
PROJECTED ACCRUAL: A total of 30 people will be accrued for this study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description cisplatin & RAD001 immunohistochemistry staining method This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors cisplatin & RAD001 gene expression analysis This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors cisplatin & RAD001 biopsy This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors cisplatin & RAD001 pharmacological study This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors cisplatin & RAD001 laboratory biomarker analysis This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors cisplatin & RAD001 cisplatin This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors cisplatin & RAD001 everolimus This will be a single institution phase I study of low dose weekly cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15) plus escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle) for patients with advanced solid tumors
- Primary Outcome Measures
Name Time Method Recommended phase II dose of everolimus 1 year
- Secondary Outcome Measures
Name Time Method Pharmacokinetic profile of cisplatin and everolimus 1 year Pharmacodynamic profile of cisplatin and everolimus 1 year
Trial Locations
- Locations (1)
Memorial Sloan-Kettering Cancer Center
🇺🇸New York, New York, United States