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

NCT ID: NCT01949545

Last Updated: 2017-05-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-09-30

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.

Conditions

Solid Tumors; Hematologic Malignancies; Hepatic Impairment

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Normal Hepatic Function

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.

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: DRUG

Carfilzomib was administered by IV injection over 30 minutes

Mild Hepatic Impairment

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.

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: DRUG

Carfilzomib was administered by IV injection over 30 minutes

Moderate Hepatic Impairment

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.

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: DRUG

Carfilzomib was administered by IV injection over 30 minutes

Severe Hepatic Impairment

(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.

Group Type: EXPERIMENTAL

Carfilzomib

Intervention Type: DRUG

Carfilzomib was administered by IV injection over 30 minutes

Interventions

Carfilzomib

Carfilzomib was administered by IV injection over 30 minutes

Intervention Type: DRUG

Other Intervention Names

Kyprolis® (carfilzomib) for Injection

Eligibility Criteria

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:

#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

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

Karmanos Cancer Institute

Detroit, Michigan, United States

Duke Cancer Institute

Durham, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Evergreen Hematology and Oncology

Spokane, Washington, United States

Institut Gustave Roussy

Paris, Villejuif Cedex, France

University Medical Centre Utrecht

Utrecht, , Netherlands

Northern Ireland Cancer Trials Centre - Queen's University Belfast TriaIs Centre

Belfast, Northern Ireland, United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Velindre Hospital

Cardlff, Wales, United Kingdom

Sir Bobby Robson Cancer Trials Research Centre

Newcastle, , United Kingdom

Countries

United States; France; Netherlands; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 29026685 (View on PubMed)

Other Identifiers

20130402

Identifier Type: OTHER

Identifier Source: secondary_id

CFZ002

Identifier Type: -

Identifier Source: org_study_id