Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

Liver Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02753881
• Other study ID #: 1506016008
• Status: Completed
• Phase: Phase 1
• Start date: November 2015
• Est. completion date: December 2019

Study information

• Verified date: July 2020
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Liver Cancer
• Liver Neoplasms

Intervention

Drug:
• whole liver lobe cTACE doxorubicin
Doxorubicin CTACE administered in a whole liver lobe manner.
• superselective cTACE doxorubicin
Doxorubicin CTACE administered in a super-selective (close to the tumor) manner.

Locations

Country	Name	City	State
United States	Yale University, Department of Diagnostic Radiology	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Yale University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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)
Secondary	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