Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

Phase 1

Completed

• Conditions: Liver Cancer
• Interventions: Drug: superselective cTACE doxorubicin; Drug: whole liver lobe cTACE doxorubicin

• Registration Number: NCT02753881
• Lead Sponsor: Yale University

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.

Study Timeline

• Study Start: 2015-11
• Study First Submitted: 2016-03-10
• Study First Submitted QC: 2016-04-25
• Study First Posted: 2016-04-28
• Primary Completion: 2019-12
• Study Completion: 2019-12
• Results First Submitted: 2020-06-18
• Status Verified: 2020-07
• Results First Submitted QC: 2020-07-17
• Last Update Submitted: 2020-07-17
• Results First Posted: 2020-08-03
• Last Update Posted: 2020-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

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.

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
superselective cTACE doxorubicin	superselective cTACE doxorubicin	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.
whole liver lobe cTACE doxorubicin	whole liver lobe cTACE doxorubicin	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics Profile-- Time of Maximum Concentration	0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose	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.
Pharmacokinetics Profile-- Area Under the Concentration Time Curve	0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose	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.
Pharmacokinetics Profile-- Peak of Plasma Concentration	0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose	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.
Pharmacokinetics Profile-- Area Under the Concentration Time Curve (Dose Normalized)	0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose	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.
Pharmacokinetics Profile-- Peak of Plasma Concentration (Dose-normalized)	0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Yale University, Department of Diagnostic Radiology; 🇺🇸 New Haven, Connecticut, United States