A Phase I Study of Weekly Low-Dose Cisplatin Plus Escalating Doses of Oral RAD001(Everolimus) for Patients With Advanced Solid Tumors
- Determine the recommended phase II dose of everolimus when administered with low-dose
cisplatin in patients with advanced solid tumors.
- 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
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
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
PROJECTED ACCRUAL: A total of 30 people will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Recommended phase II dose of everolimus
Matthew G. Fury, MD, PhD
Memorial Sloan-Kettering Cancer Center
United States: Food and Drug Administration
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|