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Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02753881
Recruitment Status : Completed
First Posted : April 28, 2016
Results First Posted : August 3, 2020
Last Update Posted : August 3, 2020
Sponsor:
Information provided by (Responsible Party):
Yale University

Study Description
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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).

Condition or disease Intervention/treatment Phase
Liver Cancer Drug: whole liver lobe cTACE doxorubicin Drug: superselective cTACE doxorubicin Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacokinetics of Doxorubicin in Conventional Transarterial Chemoembolization (cTACE) of Primary and Secondary Liver Cancer
Actual Study Start Date : November 2015
Actual Primary Completion Date : December 2019
Actual Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Cancer

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: 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.
 Drug: whole liver lobe cTACE doxorubicin
Doxorubicin CTACE administered in a whole liver lobe manner.
Active Comparator: 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.
 Drug: superselective cTACE doxorubicin
Doxorubicin CTACE administered in a super-selective (close to the tumor) manner.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    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.

  2. Pharmacokinetics Profile-- Peak of Plasma Concentration [ Time Frame: 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.

  3. Pharmacokinetics Profile-- Area Under the Concentration Time Curve (Dose Normalized) [ Time Frame: 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.

  4. Pharmacokinetics Profile-- Area Under the Concentration Time Curve [ Time Frame: 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.

  5. Pharmacokinetics Profile-- Time of Maximum Concentration [ Time Frame: 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.


Secondary Outcome Measures :
  1. Number of Participants With Technical Success of cTACE Procedure. [ Time Frame: 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.

  2. 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 ]
    Adverse events assessed by CTCAE 5.0 and stratified by Lipiodol distribution. 30 patients were reviewed for toxicities.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02753881


Locations
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United States, Connecticut
Yale University, Department of Diagnostic Radiology
New Haven, Connecticut, United States, 06520
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Todd Schlachter, M.D. Yale University
  Study Documents (Full-Text)

Documents provided by Yale University:
Study Protocol and Statistical Analysis Plan  [PDF] April 20, 2017
Informed Consent Form  [PDF] April 20, 2017

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT02753881    
Other Study ID Numbers: 1506016008
First Posted: April 28, 2016    Key Record Dates
Results First Posted: August 3, 2020
Last Update Posted: August 3, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Liver Diseases
Doxorubicin
 Liposomal doxorubicin
Antibiotics, Antineoplastic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action