A Phase I/II, Non-randomized, Multi-center, Dose-escalating, Two-stage Efficacy and Feasibility Study of the Combination of Everolimus and Capecitabine in Patients With Advanced Malignancies
The results form preclinical studies suggest that mTOR inhibitors are promising drugs for
the treatment of various types of cancer. Everolimus seems the most attractive mTOR
inhibitor because of the favourable pharmacokinetic profile and possibility of oral
administration. Based on preclinical findings, mTOR inhibitors may be more efficacious when
used in a rational combination with other cancer regiments like cytostatic drugs. Indeed,
several multiagent combinations are being investigated in clinical trials at the moment, and
the results are promising.
In our study we combine everolimus, administrated twice daily at a fixed total dose of 10 mg
continuously with capecitabine administered bid for 14 days followed by 7 days rest. In
this study, capecitabine will be dose escalated. The first dose level of capecitabine is 500
mg/m2 twice daily. Three patients will be enrolled per dose level, starting at dose level 1.
If one of the 3 patients develops dose-limiting toxicity at any dose level, 3 other patients
will start at the same dose level. If 2 or more out of these 6 patients develop DLT, no
further dose escalations will be performed. The MTD will be considered to be the dose given
at the previous lower level. No intrapatient dose escalation will be applied.
Once the MTD of capecitabine is established, the phase II part of the study will start in
which 25 patients with various malignancies will be enrolled to evaluate the efficacy and
feasibility of the combination of everolimus and capecitabine.
Interventional
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Phase I part: Assessment of dose limiting toxicity and maximum tolerated dose. II part: efficacy and feasibility. Primary endpoint of the study will be response rate.
Three patients will be enrolled per dose level, starting at dose level 1. If one of the 3 patients develops dose-limiting toxicity at any dose level, 3 other patients will start at the same dose level. If 2 or more out of these 6 patients develop DLT, no further dose escalations will be performed. The MTD will be considered to be the dose given at the previous lower level. No intrapatient dose escalation will be applied.
During treatment: assessments on day 1 every cycle (3 weeks). After treatment: every 3 months during the first 2 years, and every 6 months thereafter
Yes
Hanneke Wilmink, MD, PhD
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
AMCmedonc08/010
NCT01079702
April 2008
January 2011
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