Observational Prospective Study on Chemoembolization With Doxorubicin for Unresectable Hepatocellular Carcinoma (DEBDOX)

Observational Prospective Study on Chemoembolization Using Doxorubicin Drug-eluting Bead in Patients With Unresectable Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer in men and the seventh in women and is the third most common cause of death from cancer worldwide. The overall incidence of HCC remains high in developing countries and is steadily rising in most industrialized countries.

TACE with Doxorubicin-eluting beads (DEB-TACE) has recently been developed as a novel therapy option for HCC. In order to maximize its therapeutic efficacy, doxorubicin-loaded beads were developed to deliver higher doses of the chemotherapeutic agent and to prolong its permanence within the tumor. The comparison of efficacy and safety of TACE with drug-eluting microspheres in comparison with conventional TACE (cTACE) showed that response and time to progression in the group was significantly higher than that of the cTACE group. TACE with drug-eluting microspheres thus appears to be a feasible and promising approach to the treatment of HCC.

This study's purpose is evaluating treatment efficacy, survival rate and safety of TACE using drug-eluting microspheres loaded with doxorubicin for unresectable hepatocellular carcinoma.

Study Overview

• Status: Unknown
• Conditions: Liver Cell Carcinoma Non-resectable

Detailed Description

This study's purpose is to assess treatment efficacy, survival rate and safety of TACE using drug-eluting microspheres loaded with doxorubicin for unresectable hepatocellular carcinoma.

Study Design: Prospective observational study . Primary objective: To collect data on tumor response after administration of drug-eluting microspheres that were preloaded with doxorubicin.

Secondary objectives: To collect data on survival rate, time to progression, tolerability of treatment, number of treatment required to achieve objective response and improvement of quality of life.

Treatment method:

Day -1 Doxorubicin at a dose of 35/50 mg/m2 has been charged onto 2 ml of microspheres at Pharmacy. It is suggested to dissolve Doxorubicin powder with 2 ml of contrast medium. The charging time of microspheres is at least 30 minutes.

Day 0: prehydration, antibiotic prophylaxis and setting up of a therapeutic scheme appropriate for analgesic prophylaxis (3-day duration) as previously reported (17)

Day +1:

Upon admittance to the radiology room, 1 vial of tropisetron (diluted in 100ml of physiological solution) and 1 vial of morphine hydrochloride diluted in 100 ml i.v. are administered by slow drip.

One vial of morphine hydrochloride diluted in 100 ml i.v. to be repeated one hour after the procedure and if necessary also after 6 hours.

Tropisetron i.v. if needed. Intra-arterial premedication (optional) with 1 vial of verapamil diluted in 4 ml of normal saline solution followed by 4 ml of lidocaine.

Tumor Infusion (segment/s with dominant disease) of Doxorubicin at a dose of 35/50 mg/m2 preloaded into 2 ml of 70-150 µm M1 microspheres.

A second tumor infusion is allowed if other lesions are present (daughter tumor), using Doxorubicin at a dose of 35/50 mg/m2 preloaded into 2 ml of 70-150 µm M1 microspheres (following radiologist and oncologist ' s planning of cure).

Day +30: The above procedure is repeated. Day +90: In case of response, a third administration following the above procedures will be repeated

Evaluation of response Response is assessed at 30, 90 and 180 days after TACE, monitoring tumor dimension using Chest-abdomen CAT scan with and without contrast medium, and cancer markers (CEA, Carbohydrate Antigen (CA) 19.9) Tumor response is performed according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria.

Assessment of quality of life Assessment of quality of life with alliative Performance Scale PPSv2 is performed during the baseline visit and 30, 60 and 180 days after treatment.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

Study Locations

• Italy
  • PU
    • Pesaro, PU, Italy, 61122
      • Recruiting
      • Azienda Ospedaliera Ospedali Riuniti Marche Nord, Presidio Ospedaliero San Salvatore
      • Contact: Giammaria Fiorentini, MD; Phone Number: +390721364124; Email: giammaria.fiorentini@ospedalimarchenord.it
      • Principal Investigator: Giammaria Fiorentini, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

primary care clinic

Description

Inclusion Criteria:

1. Patients with confirmed diagnosis of HCC
2. Patient with HCC not suitable for radical therapies such as resection, liver transplantation or percutaneous therapies or patient is indicated for these therapies but there is a contraindication for them or patient rejects the above treatments
3. Multinodular or single nodular tumor more than 5cm
4. Hypervascular lesion showing contrast enhancement in the early stage after contrast media injection during CT or MRI.
5. At least one uni-dimensional lesion measurable according to the Modified RECIST criteria by CT-scan or MRI
6. No invasion in the blood vessel (hepatic portal, hepatic vein) or bile duct
7. Eastern Cooperative Oncology Group performance status is 0 - 1
8. Proper blood, liver, renal, heart functionality
9. more than 18 years old
10. Expected survival more than 6 months
11. Prior written consent

Exclusion Criteria:

1. Extrahepatic metastasis (Any lymph nodes measuring ≥ 10mm along the short axis)
2. Tumor burden involving more than 50% of the liver
3. History of biliary tract repair or endoscopic biliary tract treatment
4. Clinically important refractory ascites or pleural fluid
5. Any contraindications for hepatic embolization procedures
6. Any contraindication for doxorubicin administration
7. Contrast media allergy contraindicating angiography
8. Acute or active cardiac, hepatic or renal diseases
9. Pregnant, nursing or childbearing age women and men who are sexually active and don't want to or can't do contraception

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

doxorubicin; Day +1: Lobar Infusion ( lobe with dominant disease) of Doxorubicin preloaded into 2 ml of drug-eluting microspheres. Second lobar infusion of Doxorubicin preloaded into 2 ml of drug eluting microspheres can be administered at the same time contralaterally or in a further TACE Day +30: The above procedure is repeated. Day +90: In case of response, a third administration following the above procedures will be repeated

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
tumor response	CT scan evaluation according to RECIST 1.1	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival rate	patients alive after 12 months	one year
time to progression	time from start of therapy to progression	1 year

Collaborators and Investigators

• Sponsor: International Group of Endovascular Oncology
• Investigators: Principal Investigator: Giammaria Fiorentini, MD, International Group of Endovascular Oncology

Publications and helpful links

General Publications

• Fiorentini G. A new tool to enhance the efficacy of chemoembolization to treat primary and metastatic hepatic tumors. Expert Opin Drug Deliv. 2011 Apr;8(4):409-13. doi: 10.1517/17425247.2011.565327. Epub 2011 Mar 18.
• Fiorentini G, Campanini A, Dazzi C, Davitti B, Graziani G, Priori T, Ricci Bitti R, Angelini L. Chemoembolization in liver malignant involvement. Experiences on 17 cases. Minerva Chir. 1994 Apr;49(4):281-5.

Helpful Links

• International group of endovascular oncology (IGEVO) website

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: June 26, 2013
• First Submitted That Met QC Criteria: June 28, 2013
• First Posted (Estimate): July 3, 2013

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Hepatocellular carcinoma, doxorubicin, chemoembolization
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: DEBDOX01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No