An Open-Label, Single Arm, Phase 1 Study of the Pharmacokinetics and Safety of Carfilzomib in Subjects with Advanced Malignancies and Varying Degrees of Hepatic Impairment

Completed

• Conditions: advanced cancer; liver impairment; 10019654; 10027655

• Registration Number: NL-OMON41294
• Lead Sponsor: Onyx Therapeutics, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 29 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 5

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<=10) must meet all inclusion criteria as outlined with the exception of Inclusion Criterion #5, which should be substituted with the following criterion to be enrolled into the study: ;- Cohort 1 (normal hepatic function): Bilirubin * ULN; AST * ULN ;6. ECOG Performance Status 0-2;7. Left ventricular ejection fraction (LVEF) * 40 within 21 days prior to enrollment;8. Adequate renal function (calculated creatinine clearance *30mL/min)

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)

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To assess the influence of hepatic impairment on area under the curve (both<br /><br>area under the curve, from time 0 to the last concentration measured<br /><br>[AUC0-last] and area under the curve, from time 0 extrapolated to infinity<br /><br>[AUC0-inf]) of carfilzomib at Cycle 1 Day 16 (C1D16) in subjects with relapsed<br /><br>or progressive advanced malignancies.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- To compare, between subject cohorts, additional pharmacokinetics (PK)<br /><br>parameters at C1D16, including maximum plasma concentration (Cmax), time to<br /><br>maximum concentration (tmax), clearance (CL), terminal half-life (t1/2), volume<br /><br>of distribution at steady state (Vss), and mean residence time (MRT)<br /><br>- To compare, between subject cohorts, PK parameters at Cycle 2 Day 1 (C2D1),<br /><br>including AUC0-last, AUC0-inf, Cmax, tmax, CL, t1/2,<br /><br>Vss, and MRT<br /><br>- To evaluate PK parameters for major metabolites (metabolites PR-389/M14,<br /><br>PR-413/M15, and PR-519/M16) including AUC0-last, AUC0-inf, Cmax, tmax, t1/2,<br /><br>and MRT<br /><br>- To evaluate the safety and tolerability of carfilzomib</p><br>