A Phase 1 interventional study of cisplatin and everolimus in Unspecified Adult Solid Tumor, Protocol Specific, sponsored by Memorial Sloan Kettering Cancer Center. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-05-25.
Sponsored by Memorial Sloan Kettering Cancer Center · Phase 1, Interventional, and Treatment
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.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a dose-escalation study of everolimus (part A) followed by a biological marker study (part B).
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.
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.
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DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
Advanced solid tumor (part A)
Solid tumor (part B)
No uncontrolled brain or leptomeningeal metastases
PATIENT CHARACTERISTICS:
No impaired gastrointestinal function or gastrointestinal disease that may alter the absorption of everolimus, including any of the following:
No other concurrent severe and/or uncontrolled medical disease that would compromise study participation, including any of the following:
PRIOR CONCURRENT THERAPY:
No concurrent chronic steroid treatment (> 5 mg/day of prednisone)
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
Drug: cisplatin · Drug: everolimus · Genetic: gene expression analysis · Other: immunohistochemistry staining method · Other: laboratory biomarker analysis · Other: pharmacological study · Procedure: biopsy
cisplatin (20 mg/m2 intravenously on Days 1, 8, and 15)
escalating doses of daily RAD001 tablets (per oral or via percutaneous gastrostomy tube, Days 1 -21 of a 28-Day Cycle)
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.
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
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)
For patients in Part A, research bloods for pharmacokinetics are drawn on Day 1 and Day 8.
"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.
Recommended phase II dose of everolimus
Time frame: 1 year
Pharmacokinetic profile of cisplatin and everolimus
Time frame: 1 year
Pharmacodynamic profile of cisplatin and everolimus
Time frame: 1 year
This study is completed, as verified in Sep 2012. You cannot join it, but the record below documents what was studied.
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Memorial Sloan Kettering Cancer Center