Neoplasms

Blood and Lymph Conditions

All Conditions

Digestive System Diseases

Hematologic Neoplasms

Liver Diseases

Hematologic Diseases

Gastrointestinal Diseases

All Drugs and Chemicals

Amino Acids

Bilirubin

N-Methylaspartate

Aspartic Acid

Participants with normal hepatic function (bilirubin and aspartate aminotransferase (AST) ≤ the upper limit of normal (ULN)) received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on days 1 and 2 of cycle 1, followed by a planned step-up to 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² in cycle 1 received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15, and 16 of cycle 2 and subsequent 28-day cycles until confirmed progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death.

Participants with mild hepatic impairment (bilirubin \> 1-1.5 x ULN or AST \> ULN, but bilirubin ≤ ULN) received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on days 1 and 2 of cycle 1, followed by a planned step-up to 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² in cycle 1 received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15, and 16 of cycle 2 and subsequent 28-day cycles until confirmed progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death.

Participants with moderate hepatic impairment (bilirubin \> 1.5-3 x ULN, any AST) received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on days 1 and 2 of cycle 1, followed by a planned step-up to 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² in cycle 1 received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15, and 16 of cycle 2 and subsequent 28-day cycles until confirmed progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death.

(Bilirubin \> 3 × ULN; any AST) Participants with severe hepatic impairment (bilirubin \> 3 x ULN; any AST) received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on days 1 and 2 of cycle 1, followed by a planned step-up to 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² in cycle 1 received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15, and 16 of cycle 2 and subsequent 28-day cycles until confirmed progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death.

Carfilzomib was administered by IV injection over 30 minutes

Carfilzomib

The purpose of this study is to compare the safety and efficacy of carfilzomib, including measuring the amount of the study drug in the blood at certain times following dosing. This study is being done in people with varying degrees of liver function to see if they respond differently to the study drug.

Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment

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

The area under the curve from time zero (defined as the start of carfilzomib infusion) to the last concentration measured (AUC0-last) following intravenous administration of carfilzomib 27 mg/m² on day 16 of cycle 1 was calculated using a non-compartmental approach, from the individual plasma concentration profiles of carfilzomib.

The area under the curve from time zero extrapolated to infinity (AUC0-inf) following intravenous administration of carfilzomib 27 mg/m² on day 16 of cycle 1 was calculated using a non-compartmental approach, from the individual plasma concentration profiles of carfilzomib.

The area under the curve from time zero to the last concentration measured (AUC0-last) following intravenous administration of carfilzomib 56 mg/m² on day 1 of cycle 2 was calculated using a non-compartmental approach, from the individual plasma concentration profiles of carfilzomib.

The area under the curve from time zero extrapolated to infinity (AUC0-inf) following intravenous administration of carfilzomib 56 mg/m² on day 1 of cycle 2 was calculated using a non-compartmental approach, from the individual plasma concentration profiles of carfilzomib.

Treatment-related adverse events (TRAEs) are adverse events considered related to carfilzomib by the investigator, including those with unknown relationship.

Adverse events were graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.03, on a scale from 1 (mild) to 5 (death).

Amgen

Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Normal Hepatic Function

Mild Hepatic Impairment

Moderate Hepatic Impairment

Participants with severe hepatic impairment (bilirubin \> 3 x ULN; any AST) received carfilzomib 20 mg/m² administered by intravenous (IV) infusion on days 1 and 2 of cycle 1, followed by a planned step-up to 27 mg/m² IV on days 8, 9, 15, and 16 of cycle 1. Participants who adequately tolerated dosing at 27 mg/m² in cycle 1 received carfilzomib 56 mg/m² IV on days 1, 2, 8, 9, 15, and 16 of cycle 2 and subsequent 28-day cycles until confirmed progressive disease (PD), unacceptable toxicity, withdrawal of consent, study closure, or death.

Severe Hepatic Impairment

Total

Age, Continuous

< 65 years

≥ 65 years

Age, Customized

Sex: Female, Male

Black

White

Not reported

Race/Ethnicity, Customized

Study Director

To assess the effect of hepatic impairment relative to participants with normal hepatic function on AUC0-last an analysis of variance (ANOVA) of the log-transformed plasma PK parameters was performed. The ANOVA model included hepatic impairment as a fixed effect.

To assess the effect of hepatic impairment relative to participants with normal hepatic function on AUC0-last an ANOVA of the log-transformed plasma PK parameters was performed. The ANOVA model included hepatic impairment as a fixed effect.

Pharmacokinetic-evaluable population, defined as participants who received the intended carfilzomib dose (27 or 56 mg/m²) and who had plasma concentration versus time data for the estimation of each pharmacokinetic (PK) parameter by a non-compartmental analysis.

Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) of Carfilzomib 27 mg/m²

To assess the effect of hepatic impairment relative to participants with normal hepatic function on AUC0-inf an ANOVA of the log-transformed plasma PK parameters was performed. The ANOVA model included hepatic impairment as a fixed effect.

Pharmacokinetic-evaluable population with data to allow terminal phase characterization

Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carfilzomib 27 mg/m²

Maximum Plasma Concentration (Cmax) of Carfilzomib 27 mg/m²

Time to Maximum Plasma Concentration (Tmax) of Carfilzomib 27 mg/m²

Clearance of Carfilzomib 27 mg/m²

Terminal Half-life of Carfilzomib 27 mg/m²

Mean Residence Time (MRT) of Carfilzomib 27 mg/m²

Volume of Distribution at Steady State (Vss) of Carfilzomib 27 mg/m²

Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) of Carfilzomib 56 mg/m²

Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carfilzomib 56 mg/m²

Maximum Plasma Concentration (Cmax) of Carfilzomib 56 mg/m²

Time to Maximum Plasma Concentration (Tmax) of Carfilzomib 56 mg/m²

Terminal Half-life of Carfilzomib 56 mg/m²

Clearance of Carfilzomib 56 mg/m²

Mean Residence Time (MRT) of Carfilzomib 56 mg/m²

Volume of Distribution at Steady State (Vss) of Carfilzomib 56 mg/m²

Cycle 1 Day 16 (27 mg/m²); N = 10, 14, 9, 0

Cycle 2 Day 1 (56 mg/m²); N = 8, 8, 5, 0

Pharmacokinetic-evaluable population, defined as all participants who had adequate carfilzomib exposure and plasma concentration versus time data for the estimation of PK parameters by a non-compartmental analysis at each time point.

Spots Global Cancer Trial Database for Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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