Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment
Condition: Solid Tumors; Hematologic Malignancies; Hepatic Impairment
MeSH terms: Neoplasms; Hematologic Neoplasms; Liver Diseases
Intervention: Carfilzomib
Intervention description: Carfilzomib was administered by IV injection over 30 minutes
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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.
    

Eligibility 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 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

          6. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

          7. Left ventricular ejection fraction (LVEF) ≥ 40%

          8. Adequate renal function (calculated creatinine clearance ≥ 30 mL/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 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)