advanced cancer liver impairment
Conditions
Interventions
Carfilzomib will be administered over 30 minutes (± 5 minutes) as an
intravenous (IV) infusion on Days 1, 2, 8, 9, 15, and 16 of a 28-day cycle.
For Cycle 1, subjects will receive carfilzomib 20 mg/m
Sponsors
Onyx Therapeutics, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Relapsed or progressive advanced malignancies (solid tumors or hematologic malignancies);2. At least 2 prior treatment regimens for the underlying malignancy;3. Histologically or cytologically confirmed advanced solid tumor or hematologic malignancy;4. Measurable or evaluable disease;5. Clinical diagnosis of chronic hepatic impairment that is stable with no acute worsening of liver failure within one month prior to enrollment. Hepatic impairment will be assessed as per NCI-ODWG schema and will fall into one of the following three categories:;- Cohort 2 (mild): Bilirubin > 1*1.5 × upper limit of the normal range (ULN) or aspartate aminotransferase (AST) > ULN, but bilirubin * ULN;- Cohort 3 (moderate): * 1.5*3 × ULN; any AST;- Cohort 4 (severe): Bilirubin > 3 × ULN; any AST;Exception to Inclusion Criterion #5 for Subjects with Normal Hepatic Function:;All subjects enrolled with normal hepatic function (N
Exclusion criteria
Exclusion criteria: 1. Subjects with symptomatic brain metastasis or central nervous system [CNS] disease;2. Significant neurotoxicity (Grade 2 with pain or higher) at the time of enrolment;3. Known HIV, Hepatitis B virus and Hepatitis C virus infection (Exception: Subjects with chronic or cleared HBV and HCV infection and stable liver function tests [bilirubin, AST] will be allowed)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the influence of hepatic impairment on area under the curve (both area under the curve, from time 0 to the last concentration measured [AUC0-last] and area under the curve, from time 0 extrapolated to infinity [AUC0-inf]) of carfilzomib at Cycle 1 Day 16 (C1D16) in subjects with relapsed or progressive advanced malignancies. | — |
Secondary
| Measure | Time frame |
|---|---|
| - To compare, between subject cohorts, additional pharmacokinetics (PK) parameters at C1D16, including maximum plasma concentration (Cmax), time to maximum concentration (tmax), clearance (CL), terminal half-life (t1/2), volume of distribution at steady state (Vss), and mean residence time (MRT) - To compare, between subject cohorts, PK parameters at Cycle 2 Day 1 (C2D1), including AUC0-last, AUC0-inf, Cmax, tmax, CL, t1/2, Vss, and MRT - To evaluate PK parameters for major metabolites (metabolites PR-389/M14, PR-413/M15, and PR-519/M16) including AUC0-last, AUC0-inf, Cmax, tmax, t1/2, and MRT - To evaluate the safety and tolerability of carfilzomib | — |
Countries
Netherlands
Outcome results
None listed