Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

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Primary Purpose

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

whole liver lobe cTACE doxorubicin

superselective cTACE doxorubicin

About this trial

This is an interventional treatment trial for Liver Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Yale University, Department of Diagnostic Radiology

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

whole liver lobe cTACE doxorubicin

superselective cTACE doxorubicin

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

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.

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.

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.

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT02753881

First Posted

March 10, 2016

Last Updated

July 17, 2020

Sponsor

Yale University

1. Study Identification

Unique Protocol Identification Number

NCT02753881

Brief Title

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

2. Study Status

Record Verification Date

July 2020

Overall Recruitment Status

Completed

Study Start Date

November 2015 (Actual)

Primary Completion Date

December 2019 (Actual)

Study Completion Date

December 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Yale University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

No

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

30 (Actual)

8. Arms, Groups, and Interventions

Arm Title

whole liver lobe cTACE doxorubicin

Arm Type

Active Comparator

Arm 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.

Arm Title

superselective cTACE doxorubicin

Arm Type

Active Comparator

Arm 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.

Intervention Type

Drug

Intervention Name(s)

whole liver lobe cTACE doxorubicin

Intervention Description

Doxorubicin CTACE administered in a whole liver lobe manner.

Intervention Type

Drug

Intervention Name(s)

superselective cTACE doxorubicin

Intervention Description

Doxorubicin CTACE administered in a super-selective (close to the tumor) manner.

Primary Outcome Measure Information:

Title

Pharmacokinetics Profile-- Peak of Plasma Concentration (Dose-normalized)

Description

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.

Time Frame