Study of the Pharmacokinetics and Safety of Carfilzomib in Subjects With Advanced Malignancies and Hepatic Impairment
Solid Tumors - Hematologic Malignancies - Hepatic Impairment
Conditions: official terms
Liver Diseases - Neoplasms
Study Type
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Parallel Assignment, Masking: Open Label
Name: Carfilzomib
Type: Drug
Overall Status
The purpose of this study is to compare the safety and efficacy of an investigational drug called 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.
Detailed Description
The primary objective of this study is 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.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Key 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. 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): ≥ 1.6-3 × 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

6. ECOG Performance Status 0-2

7. Left ventricular ejection fraction (LVEF) ≥ 40%

8. Adequate renal function (calculated creatinine clearance ≥ 30mL/min)

9. 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:

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)
Karmanos Cancer Institute
Detroit, Michigan, United States
Status: Recruiting
Duke Cancer Institute
Durham, North Carolina, United States
Status: Recruiting
Gabrail Cancer Center
Canton, Ohio, United States
Status: Recruiting
Tennessee Oncology, PLLC
Nashville, Tennessee, United States
Status: Recruiting
Evergreen Hematology and Oncology
Spokane, Washington, United States
Status: Terminated
Institut Gustave Roussy
Paris, Villejuif Cedex, France
Status: Recruiting
University Medical Centre Utrecht
Utrecht, Netherlands
Status: Recruiting
Northern Ireland Cancer Trials Centre - Queen's University Belfast TriaIs Centre
Belfast, Northern Ireland, United Kingdom
Status: Recruiting
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom
Status: Recruiting
Velindre Hospital
Cardlff, Wales, United Kingdom
Status: Recruiting
Sir Bobby Robson Cancer Trials Research Centre
Newcastle, United Kingdom
Status: Recruiting
Start Date
October 2013
Completion Date
September 2017
Onyx Therapeutics, Inc.
Onyx Pharmaceuticals
Record processing date processed this data on July 28, 2015 page