Clinical trial NCT02753881: Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer
Official title: Pharmacokinetics of Doxorubicin in Conventional Transarterial Chemoembolization (cTACE) of Primary and Secondary Liver Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Liver Cancer
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2016-04-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Pharmacokinetics Profile-- Peak of Plasma Concentration (Dose-normalized)
timeFrame: 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose
measure: Pharmacokinetics Profile-- Peak of Plasma Concentration
timeFrame: 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose
measure: Pharmacokinetics Profile-- Area Under the Concentration Time Curve (Dose Normalized)
timeFrame: 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose
measure: Pharmacokinetics Profile-- Area Under the Concentration Time Curve
timeFrame: 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose
measure: Pharmacokinetics Profile-- Time of Maximum Concentration
timeFrame: 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose
Secondary outcomes:
measure: Number of Participants With Technical Success of cTACE Procedure.
timeFrame: assessed at baseline (at the time of the cTACE procedure)
measure: Assessment and Frequency of Toxicities (Laboratory and Clinical Adverse Events) According to NCI Common Toxicity Criteria for AE (CTCAE) 5.0.
timeFrame: up to 4 weeks post cTACE
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale University, Department of Diagnostic Radiology
state: Connecticut
Study officials:
affiliation: Yale University
name: Todd Schlachter, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Savic LJ, Chapiro J, Funai E, Bousabarah K, Schobert IT, Isufi E, Geschwind JH, Stark S, He P, Rudek MA, Perez Lozada JC, Ayyagari R, Pollak J, Schlachter T. Prospective study of Lipiodol distribution as an imaging marker for doxorubicin pharmacokinetics during conventional transarterial chemoembolization of liver malignancies. Eur Radiol. 2021 May;31(5):3002-3014. doi: 10.1007/s00330-020-07380-w. Epub 2020 Oct 15.