The investigators hypothesize that certain mutations in the individual cancer genomes will predict response to Everolimus therapy. To identify possible genetic mutations that affect tumor response to Everolimus the investigators will obtain sequence analysis of tumors from all patients that will be treated with Everolimus in this study. Moreover, the investigators performed a systematic review of the currently available data to identify mutations that could be predictive for increased mTOR activity in cancer cells. These mutations have been described to lead to mTOR activation but their predictive value for response to Everolimus therapy remains unclear. The investigators will use the data generated in the investigators own prospective treatment study and the data from literature to select patients for entry into a second part of this trial. In this part the investigators want to test the hypothesis that selecting patients based on their specific genetic mutations increases the likelihood of response.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
OTHER
Masking
NONE
Enrollment
73
All patients will receive everolimus 10mg q.d.
NKI-AVL
Amsterdam, North Holland, Netherlands
Erasmus Medical Center
Rotterdam, South Holland, Netherlands
University Medical Center Utrecht
Utrecht, Netherlands
analyse a set of 1951 genes for prediction of response measured by time to progression (TTP) ratio (defined as the TTP without drug: TTP on drug) on mTOR inhibition.
Inclusion until earliest date of disease progression (defined as a 30% volumetric increase in tumorvolume or appearance of new lesions)
Time frame: An expected average of 5 months
Progression free survival
Time from initiation of everolimus to, either radiological (RECIST 1.1) or clinical disease progression or death from any cause.
Time frame: An expected average of 4 months
Disease control rate (DCR)
Disease control rate (DCR) (DC = CR or PR or SD) as defined by RECIST 1.1 3 months after initiation of Everolimus.
Time frame: At 3 months after initiation of everolimus
Toxicity
Toxicity will be assessed according to the Common Toxicity Criteria for Adverse Events (CTCAE) version v4.03: June 14, 2010
Time frame: An expected average of 6 months
Median overall survival
The (median) time from initiation of Everolimus to time of death or censored at the date of last follow-up. First analysis of overall survival will be performed within one year after inclusion of last subject.
Time frame: An expected average of one year
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