Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

Yale University30 enrolled

Overview

Patients with primary and secondary liver cancer may participate in this study. The purpose is to perform an analysis of the effects of doxorubicin and its metabolite doxorubicinol on the body (doxorubicin pharmacokinetics ) after conventional transarterial chemoembolization (cTACE). cTACE is a procedure in which chemotherapy drugs are injected, followed by an injection of small beads to block the tumor-feeding arteries. Doxorubicin is a chemotherapeutic agent used in the cTACE procedure. This study will examine doxorubicin pharmacokinetics in patients who: 1) receive whole liver cTACE; and 2) receive super-selective CTACE (i.e., delivered in close proximity to the tumor).

Patients with primary and secondary liver cancer may participate in this study. The purpose is to perform an analysis of the effects of doxorubicin and its metabolite doxorubicinol on the body (doxorubicin pharmacokinetics ) after conventional transarterial chemoembolization (cTACE). A pharmacokinetics profile (PK profile) will be constructed and will include peak of plasma concentration (Cmax), time of maximum concentration (TMax), and area under the concentration curve (AUC). This composite measure will be used to compare patients in cTACE lobar administration and cTACE superselective administration. In addition, the PK profile will be correlated with toxicity, tumor burden, body surface area, and gender. Feasibility and safety will also be assessed.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Liver Cancer

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥ 18 years. 2. Histologically, cytologically, or radiologically confirmed liver dominant or liver only malignancy. 3. Preserved liver function (Child-Pugh A-B class) without significant liver decompensation. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at study entry. 5. Measurable or evaluable disease that will be directly treated with intrahepatic therapy (as defined by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1). 6. Suitable for TACE based on blood parameters such as platelet count, bilirubin, and international normalized ratio. 7. May be enrolled with a history of prior liver directed intra-arterial therapy if intra-arterial therapy to the target lesion occured \> 1 year prior to enrollment date. Intra-arterial therapy to different targets within 1 year prior to enrollment date will not exclude subjects. Exclusion Criteria: 1. Serum total bilirubin \> 3.0 mg/dL 2. Creatinine \> 2.0 mg/dL 3. Platelets \< 50000/µL 4. Complete portal vein thrombosis with reversal of flow 5. Ascites (trace ascites on imaging is acceptable)

Outcomes

Primary Outcomes

Pharmacokinetics Profile-- Peak of Plasma Concentration (Dose-normalized)

Peak of plasma concentration (Cmax) of both doxorubicin and doxorubicinol reported for 10 lobar subjects, 10 superselective subjects with Lipiodol distribution to 1 segment, and 10 superselective subjects with Lipiodol distribution to multiple segments after dose normalization.