0C-14-4 A Phase I, multi-center, non-randomized, open label, parallel-group study evaluating the pharmacokinetics and safety of regorafenib (BAY 73-4506) in cancer subjects with severe renal impairment compared to a control group
Regorafenib is a targeted agent that has been shown to have anti-cancer activity and has been approved for use in previously treated patients with advanced colorectal cancer and gastrointestinal stromal tumors. Regorafenib is processed in the body or metabolized mostly through the liver, but the FDA recommends that a pharmacokinetic (PK) study be conducted in patients with damaged kidney function since damaged kidney function can alter the PK of the drug. PK studies look at what the body does to the drug in terms of how it is absorbed, distributed, metabolized, and excreted. The PK of regorafenib has been studied in patients with mild kidney damage, but not in patients with severe kidney damage or end-stage kidney disease. This open-label, Phase 1 study is being done with a primary objective to evaluate the impact of severe kidney damage on the PK of regorafenib in subjects with advanced solid tumors as compared to those with normal kidney function. There will be 2 groups of kidney function evaluated (Group 1 Control: normal/mild damage, Group 2: severe damage).
Once patients have signed consent and are deemed eligible, they will be assigned to one of two groups according to their kidney function status. Each group will have a minimum of 12 subjects. The study will be done in 2 stages. In the first stage, all subjects will receive one dose of regorafenib and have PK bloods collected for up to 4 days. They will enter into the second phase if they are willing and the study doctor thinks that they will benefit. They will continue to have study visits and receive study drug until they have side effect(s) or a condition which necessitates their removal from the study, they are lost to follow up, their disease progresses, they become pregnant, the protocol is not followed, they withdraw consent, their study doctor thinks that being on the study is no longer in their best interest, or the sponsor stops the study.
The PK and safety data will be summarized and analyzed by kidney function group. Summary statistics will be presented by treatment group. Medical history findings will be summarized for all subjects. The primary pharmacokinetic analysis will be based on classification of renal function using the C-G formula. The following statistics will be calculated for each of the PK sampling points and characteristics: arithmetic mean, standard deviation and coefficient of variation (CV), geometric mean, geometric standard deviation (re-transformed standard deviation of the logarithms) and CV, minimum, median, maximum value and the number of measurements. Individual and geometric mean concentration vs. time curves of all analytes will be plotted by treatment using both linear and semilogarithmic scale. To compare the two kidney function groups, AUC(0-24)md estimated with nominal dosing will be analyzed assuming log-normally distributed data.
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