Clinical trial NCT00423865: Cisplatin and Everolimus in Treating Patients With Advanced Solid Tumors
Official title: A Phase I Study of Weekly Low-Dose Cisplatin Plus Escalating Doses of Oral RAD001(Everolimus) for Patients With Advanced Solid Tumors
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
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.
Interventions:
description: cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15)
name: cisplatin
type: Drug
description: escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle)
name: everolimus
type: Drug
description: Each biopsy specimen will be formalin-fixed and paraffin-embedded for IHC, and analysis of p53 and p21 will follow methods previous reported by our group. The avidin-biotin immunoperoxidase technique will be employed.
name: gene expression analysis
type: Genetic
description: After the phase 2 recommended dose is established in the phase I portion of the study (Part A), we plan to enroll an additional 6 patients for pharmacodynamic studies (Part B). Entry into Part B requires the patient have tumor tissue which is easily accessible for research biopsy. The patients will be asked to provide written informed consent for the research biopsies. Patients also will be asked to provide written informed consent to allow the use of their tissue for future research studies. The research biopsies are not mandatory for any patient. Patients who do not consent to the research biopsies or who withdraw consent for the research biopsies may still receive RAD001 + cisplatin in the study
name: immunohistochemistry staining method
type: Other
description: Laboratory data (complete blood count, comprehensive metabolic panel including magnesium) regarding adverse events will be collected on each cisplatin treatment day. Additional adverse event data will be collected at regularly scheduled clinic visits at which history and physical are performed by the investigator (Cycle 1 - Days 1, 8, 15, and 21. Cycle 2 - Days 1 and 15. Cycle 3 and beyond - Day 1)
name: laboratory biomarker analysis
type: Other
description: For patients in Part A, research bloods for pharmacokinetics are drawn on Day 1 and Day 8.
name: pharmacological study
type: Other
description: "Pre-treatment Research Biopsy:" Within 14 days prior to treatment, research biopsy (of primary tumor, metastatic deposit, or involved lymph node) will be performed. Baseline labs should be drawn within 14 days of the research biopsy. The biopsy sample will be formalin-fixed and paraffin-embedded for immunohistochemistry. Post-treatment Research Biopsy:" Research biopsy (of primary tumor, metastatic deposit, or involved lymph node) will be requested again for Day 15 of Cycle 1, prior to administration of RAD001 and cisplatin on that day.
name: biopsy
type: Procedure
Study arms:
design_group_description: 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
design_group_title: cisplatin & RAD001
design_group_type: Experimental
Sponsor: Memorial Sloan Kettering Cancer Center
Collaborators: National Cancer Institute
Drug name mappings:
name: 顺铂
lang: CN
name: Cisplatin
lang: EN
name: シスプラチン
lang: JP
name: 依维莫司
lang: CN
name: Everolimus
lang: EN
name: エベロリムス
lang: JP