Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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Pharmacokinetics of Doxorubicin in Conventional Transarterial Chemoembolization (cTACE) of Primary and Secondary Liver Cancer

Conditions
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Liver Cancer

Intervention / Treatment
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* Drug: whole liver lobe cTACE doxorubicin
* Drug: superselective cTACE doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years. Histologically, cytologically, or radiologically confirmed liver dominant or liver only malignancy. Preserved liver function (Child-Pugh A-B class) without significant liver decompensation. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 at study entry. Measurable or evaluable disease that will be directly treated with intrahepatic therapy (as defined by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1). Suitable for TACE based on blood parameters such as platelet count, bilirubin, and international normalized ratio. 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: Serum total bilirubin > 3.0 mg/dL Creatinine > 2.0 mg/dL Platelets < 50000/µL Complete portal vein thrombosis with reversal of flow Ascites (trace ascites on imaging is acceptable)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: whole liver lobe cTACE doxorubicin<br>Participants in this arm are administered 10 cc of chemotherapy, with 50mg doxorubicin and 10 mg of mitomycin-C via cTACE delivered in a lobar (whole liver) manner. | Drug: whole liver lobe cTACE doxorubicin<br>* Doxorubicin CTACE administered in a whole liver lobe manner.<br>|
| Active Comparator: superselective cTACE doxorubicin<br>Participants in this arm are administered 10 cc of chemotherapy, with 50mg doxorubicin and 10 mg of mitomycin-C via cTACE delivered in a super-selective (close to the tumor) manner. | Drug: superselective cTACE doxorubicin<br>* Doxorubicin CTACE administered in a super-selective (close to the tumor) manner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose | 
| Pharmacokinetics Profile-- Peak of Plasma Concentration | Peak of plasma concentration (Cmax) of 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. | 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose | 
| Pharmacokinetics Profile-- Area Under the Concentration Time Curve (Dose Normalized) | Area under the concentration time curve (AUC) reported for 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. | 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose | 
| Pharmacokinetics Profile-- Area Under the Concentration Time Curve | Area under the concentration time curve (AUC) reported for 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. | 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose | 
| Pharmacokinetics Profile-- Time of Maximum Concentration | Median time of maximum concentration (Tmax) reported for 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. | 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Technical Success of cTACE Procedure. | Feasibility/technical success (yes/no) is measured by ability to administer a therapeutic dose, which is determined clinically. | assessed at baseline (at the time of the cTACE procedure) | 
| Assessment and Frequency of Toxicities (Laboratory and Clinical Adverse Events) According to NCI Common Toxicity Criteria for AE (CTCAE) 5.0. | Adverse events assessed by CTCAE 5.0 and stratified by Lipiodol distribution. 30 patients were reviewed for toxicities. | up to 4 weeks post cTACE |