Back to resultsStudy of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment
Primary Purpose
Solid Tumors, Hematologic Malignancies, Hepatic Impairment
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Carfilzomib
Sponsored by
About this trial
This is an interventional other trial for Solid Tumors
Eligibility Criteria
Key Inclusion Criteria:
- Relapsed or progressive advanced malignancies (solid tumors or hematologic malignancies)
- At least ≥ 2 prior treatment regimens for the underlying malignancy
- Confirmed advanced solid tumor or hematologic malignancy
- Measurable or evaluable disease
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 National Cancer Institute Organ Dysfunction Working Group Criteria (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): ≥ 1.6-3 × 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
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Left ventricular ejection fraction (LVEF) ≥ 40%
- Adequate renal function (calculated creatinine clearance ≥ 30 mL/min)
- Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within the protocol-specified period prior to enrollment
Key Exclusion Criteria:
- Subjects with symptomatic brain metastasis or central nervous system (CNS) disease
- Significant neurotoxicity (Grade 2 with pain or higher) at the time of enrolment
- Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection (Exception: Subjects with chronic or cleared HBV and HCV infection and stable liver function tests [bilirubin, AST] will be allowed)
Sites / Locations
- Karmanos Cancer Institute
- Duke Cancer Institute
- Gabrail Cancer Center
- Tennessee Oncology, PLLC
- Evergreen Hematology and Oncology
- Institut Gustave Roussy
- University Medical Centre Utrecht
- Northern Ireland Cancer Trials Centre - Queen's University Belfast TriaIs Centre
- Beatson West of Scotland Cancer Centre
- Velindre Hospital
- Sir Bobby Robson Cancer Trials Research Centre
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Normal Hepatic Function
Mild Hepatic Impairment
Moderate Hepatic Impairment
Severe Hepatic Impairment
Arm Description
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.
Outcomes
Primary Outcome Measures
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) of Carfilzomib 27 mg/m²
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.
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carfilzomib 27 mg/m²
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.
Secondary Outcome Measures
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
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.
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carfilzomib 56 mg/m²
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.
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
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) for Metabolite PR-389/M14
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Metabolite PR-389/M14
Maximum Plasma Concentration (Cmax) for Metabolite PR-389/M14
Time to Maximum Plasma Concentration (Tmax) for Metabolite PR-389/M14
Terminal Half-life for Metabolite PR-389/M14
Mean Residence Time (MRT) for Metabolite PR-389/M14
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) for Metabolite PR-413/M15
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Metabolite PR-413/M15
Maximum Plasma Concentration (Cmax) for Metabolite PR-413/M15
Time to Maximum Plasma Concentration (Tmax) for Metabolite PR-413/M15
Terminal Half-life for Metabolite PR-413/M15
Mean Residence Time (MRT) for Metabolite PR-413/M15
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) for Metabolite PR-519/M16
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Metabolite PR-519/M16
Maximum Plasma Concentration (Cmax) for Metabolite PR-519/M16
Time to Maximum Plasma Concentration (Tmax) for Metabolite PR-519/M16
Terminal Half-life for Metabolite PR-519/M16
Mean Residence Time (MRT) for Metabolite PR-519/M16
Number of Participants With Adverse Events (AEs)
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01949545
Brief Title
Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
August 2015 (Actual)
Study Completion Date
September 2015 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Solid Tumors, Hematologic Malignancies, Hepatic Impairment
7. Study Design
Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
46 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Normal Hepatic Function
Arm Type
Experimental
Arm Description
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.
Arm Title
Mild Hepatic Impairment
Arm Type
Experimental
Arm Description
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.
Arm Title
Moderate Hepatic Impairment
Arm Type
Experimental
Arm Description
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.
Arm Title
Severe Hepatic Impairment
Arm Type
Experimental
Arm Description
(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.
Intervention Type
Drug
Intervention Name(s)
Carfilzomib
Other Intervention Name(s)
Kyprolis® (carfilzomib) for Injection
Intervention Description
Carfilzomib was administered by IV injection over 30 minutes
Primary Outcome Measure Information:
Title
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) of Carfilzomib 27 mg/m²
Description
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.
Time Frame
Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carfilzomib 27 mg/m²
Description
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.
Time Frame
Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Secondary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of Carfilzomib 27 mg/m²
Time Frame
Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Time to Maximum Plasma Concentration (Tmax) of Carfilzomib 27 mg/m²
Time Frame
Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Clearance of Carfilzomib 27 mg/m²
Time Frame
Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Terminal Half-life of Carfilzomib 27 mg/m²
Time Frame
Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Mean Residence Time (MRT) of Carfilzomib 27 mg/m²
Time Frame
Cycle 1 day 16, pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Volume of Distribution at Steady State (Vss) of Carfilzomib 27 mg/m²
Time Frame
Cycle 1 day 16 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) of Carfilzomib 56 mg/m²
Description
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.
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Carfilzomib 56 mg/m²
Description
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.
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Maximum Plasma Concentration (Cmax) of Carfilzomib 56 mg/m²
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Time to Maximum Plasma Concentration (Tmax) of Carfilzomib 56 mg/m²
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Terminal Half-life of Carfilzomib 56 mg/m²
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Clearance of Carfilzomib 56 mg/m²
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Mean Residence Time (MRT) of Carfilzomib 56 mg/m²
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Volume of Distribution at Steady State (Vss) of Carfilzomib 56 mg/m²
Time Frame
Cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) for Metabolite PR-389/M14
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Metabolite PR-389/M14
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Maximum Plasma Concentration (Cmax) for Metabolite PR-389/M14
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Time to Maximum Plasma Concentration (Tmax) for Metabolite PR-389/M14
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Terminal Half-life for Metabolite PR-389/M14
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Mean Residence Time (MRT) for Metabolite PR-389/M14
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) for Metabolite PR-413/M15
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Metabolite PR-413/M15
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Maximum Plasma Concentration (Cmax) for Metabolite PR-413/M15
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Time to Maximum Plasma Concentration (Tmax) for Metabolite PR-413/M15
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Terminal Half-life for Metabolite PR-413/M15
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Mean Residence Time (MRT) for Metabolite PR-413/M15
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero to Last Concentration Measured (AUC0-last) for Metabolite PR-519/M16
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Area Under the Concentration Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) for Metabolite PR-519/M16
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Maximum Plasma Concentration (Cmax) for Metabolite PR-519/M16
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Time to Maximum Plasma Concentration (Tmax) for Metabolite PR-519/M16
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Terminal Half-life for Metabolite PR-519/M16
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Mean Residence Time (MRT) for Metabolite PR-519/M16
Time Frame
Cycle 1 day 16 and cycle 2 day 1 pre-dose, 15 minutes after the start of infusion, immediately (within 2 minutes) before the end of infusion, and at 5, 15, and 30 minutes and 1, 2, and 4 hours after the end of the infusion.
Title
Number of Participants With Adverse Events (AEs)
Description
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).
Time Frame
From the first dose of carfilzomib until 30 days after last dose; the overall median duration of treatment was 4.2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Relapsed or progressive advanced malignancies (solid tumors or hematologic malignancies)
At least ≥ 2 prior treatment regimens for the underlying malignancy
Confirmed advanced solid tumor or hematologic malignancy
Measurable or evaluable disease
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 National Cancer Institute Organ Dysfunction Working Group Criteria (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): ≥ 1.6-3 × 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
Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
Left ventricular ejection fraction (LVEF) ≥ 40%
Adequate renal function (calculated creatinine clearance ≥ 30 mL/min)
Active congestive heart failure (New York Heart Association [NYHA] Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction within the protocol-specified period prior to enrollment
Key Exclusion Criteria:
Subjects with symptomatic brain metastasis or central nervous system (CNS) disease
Significant neurotoxicity (Grade 2 with pain or higher) at the time of enrolment
Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infection (Exception: Subjects with chronic or cleared HBV and HCV infection and stable liver function tests [bilirubin, AST] will be allowed)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
Duke Cancer Institute
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
Country
United States
Facility Name
Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Evergreen Hematology and Oncology
City
Spokane
State/Province
Washington
Country
United States
Facility Name
Institut Gustave Roussy
City
Paris
State/Province
Villejuif Cedex
Country
France
Facility Name
University Medical Centre Utrecht
City
Utrecht
Country
Netherlands
Facility Name
Northern Ireland Cancer Trials Centre - Queen's University Belfast TriaIs Centre
City
Belfast
State/Province
Northern Ireland
Country
United Kingdom
Facility Name
Beatson West of Scotland Cancer Centre
City
Glasgow
State/Province
Scotland
Country
United Kingdom
Facility Name
Velindre Hospital
City
Cardlff
State/Province
Wales
Country
United Kingdom
Facility Name
Sir Bobby Robson Cancer Trials Research Centre
City
Newcastle
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
29026685
Citation
Brown J, Plummer R, Bauer TM, Anthony S, Sarantopoulos J, De Vos F, White M, Schupp M, Ou Y, Vaishampayan U. Pharmacokinetics of carfilzomib in patients with advanced malignancies and varying degrees of hepatic impairment: an open-label, single-arm, phase 1 study. Exp Hematol Oncol. 2017 Oct 3;6:27. doi: 10.1186/s40164-017-0086-1. eCollection 2017.
Results Reference
derived
Learn more about this trial
Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment
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