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). 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).
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
1506016008
- NCT ID:
NCT02753881
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| whole liver lobe cTACE doxorubicin | | whole liver lobe cTACE doxorubicin |
| superselective cTACE doxorubicin | | superselective cTACE doxorubicin |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| whole liver lobe cTACE doxorubicin | Active Comparator | 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. | - whole liver lobe cTACE doxorubicin
|
| superselective cTACE doxorubicin | Active Comparator | 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. | - superselective cTACE doxorubicin
|
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)
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Pharmacokinetics Profile-- Peak of Plasma Concentration (Dose-normalized) |
| Time Frame: | 0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | Number of Participants With Technical Success of cTACE Procedure. |
| Time Frame: | assessed at baseline (at the time of the cTACE procedure) |
| Safety Issue: | |
| Description: | Feasibility/technical success (yes/no) is measured by ability to administer a therapeutic dose, which is determined clinically. |
| Measure: | Assessment and Frequency of Toxicities (Laboratory and Clinical Adverse Events) According to NCI Common Toxicity Criteria for AE (CTCAE) 5.0. |
| Time Frame: | up to 4 weeks post cTACE |
| Safety Issue: | |
| Description: | Adverse events assessed by CTCAE 5.0 and stratified by Lipiodol distribution. 30 patients were reviewed for toxicities. |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Yale University |
Last Updated
August 3, 2020
