Pharmacokinetics of Doxorubicin in cTACE of Liver Cancer

NCT02753881 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 1506016008
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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).

Conditions

Liver Cancer

Outcome Measures

Primary Outcomes (5)

• 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.

  0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose

• 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.

  0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose

• 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.

  0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose

• 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.

  0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose

• 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.

  0, 5, 10, 20, 40 minutes, 1, 2, 4, 24 hours, and 3-4 weeks post dose

Secondary Outcomes (2)

• Number of Participants With Technical Success of cTACE Procedure.

  assessed at baseline (at the time of the cTACE procedure)

• 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

Study Arms (2)

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.

Drug: 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.

Drug: superselective cTACE doxorubicin

Interventions

whole liver lobe cTACE doxorubicin DRUG

Doxorubicin CTACE administered in a whole liver lobe manner.

whole liver lobe cTACE doxorubicin

superselective cTACE doxorubicin DRUG

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

superselective cTACE doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Yale University, Department of Diagnostic Radiology

New Haven, Connecticut, 06520, United States

Location

Related Publications (1)

• Savic LJ, Chapiro J, Funai E, Bousabarah K, Schobert IT, Isufi E, Geschwind JH, Stark S, He P, Rudek MA, Perez Lozada JC, Ayyagari R, Pollak J, Schlachter T. Prospective study of Lipiodol distribution as an imaging marker for doxorubicin pharmacokinetics during conventional transarterial chemoembolization of liver malignancies. Eur Radiol. 2021 May;31(5):3002-3014. doi: 10.1007/s00330-020-07380-w. Epub 2020 Oct 15.

  PMID: 33063185 DERIVED

MeSH Terms

Conditions

Liver Neoplasms

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: Todd Schlachter, MD
• Organization: Yale University

todd.schlachter@yale.edu

(203) 785-5885

Study Officials

• Todd Schlachter, M.D.

  Yale University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2016
• First Posted: April 28, 2016
• Study Start: November 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: August 3, 2020
• Results First Posted: August 3, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)