Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

Yale University

Status and phase: Completed; Phase 1

Conditions: Liver Cancer

Treatments: Drug: superselective cTACE doxorubicin; Drug: whole liver lobe cTACE doxorubicin

Study type: Interventional

Funder types: Other

Identifiers

NCT02753881

1506016008

Details and patient eligibility

About

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).

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

whole liver lobe cTACE doxorubicin

Active Comparator group

Description:

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.

Treatment:

Drug: whole liver lobe cTACE doxorubicin

superselective cTACE doxorubicin

Active Comparator group

Description:

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.

Treatment:

Drug: superselective cTACE doxorubicin