SBRT or TACE for Advanced HCC

Randomized Study of Stereotactic Body Radiation Therapy (SBRT) Versus Transarterial Chemoembolization (TACE) in Hepatocellular Carcinoma

Randomized study of stereotactic body radiation therapy (SBRT) versus transarterial chemoembolization (TACE) in locally advanced hepatocellular carcinoma.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: DEB; Radiation: SBRT

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Morten Høyer, PhD; Phone Number: +45 23282823; Email: hoyer@aarhus.rm.dk

Study Locations

• India
  • NCT
    • Delhi, NCT, India, 122001
      • Recruiting
      • Medanta
      • Contact: Tejinder Kataria, Dr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HCC (biopsy or radiological diagnostic (>1 cm, enhancing in arterial phase and wash-out in later phases).
• Number of lesions: not more than 3 lesions
• Lesion size: up to 10 cm for a single lesion (and up to 10 cm cumulative diameter, if there is more than 1 lesion)
• Child-Pugh A or B (<7) on examination within 6 weeks prior to study entry
• BCLC Stage A/B
• Must be fit (eligible) for SBRT and TACE
• Unsuitable/unwilling for resection or transplant or radiofrequency ablation (RFA) or if these options are not available
• Distance between GTV (lesion) and luminal structures (including esophagus, stomach, duodenum, small or large bowel) is >10 mm

• All blood work obtained within 2 weeks prior to study entry with adequate organ function defined as follows:

  • Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3
  • Platelets ≥50,000 cells/mm3
  • Hemoglobin ≥ 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dl is acceptable.)
  • Total bilirubin < 2 mg/dL
  • Prothrombin time/INR < 1.4 (unless on Coumadin/Warfarin)
  • Albumin ≥ 28 g/L
  • AST (and ALT) < 5 times ULN
  • Serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min
  • Left-ventricular ejection fraction >50% (cardiac ejection fraction should be measured in case of history of cardio-vascular disease.
  • May have had previous surgery, ethanol injection and RFA to the liver

Exclusion Criteria:

• • Not suitable for clinical trial or follow-up

  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (Note that carcinoma in situ of the breast, oral cavity, or cervix are all permissible). No active cancer therapy.

  • Unsuitable for or refractory to transarterial hepatic chemo-embolization (TACE)

    • Non-enhancing HCC on CT or CT-angio or
    • Portal vein thrombosis/macroscopic venous invasion
  • Arterio-portal and arterio-venous fistulas observed on pre-study imaging (if it is found during the TACE, the fistula may be embolized before injection of the drug).
  • Evidence of metastatic disease including nodal or distant metastases.
  • Previous TACE or radiation to the liver (including SIRT)

  • Life-threatening condition (including untreated HIV and active hepatitis B/C)

    • Detectable HBeAg and HBV viral load > 20,000 IU/mL or
    • HBeAg-negative chronic hepatitis B and HBV viral load >2,000 IU/mL
    • If HBV-DNA copy is higher than 500 copies/ml, anti-viral therapy, such as Entecavir followed by observation for 2 weeks.
    • If anti-HCV antibody is positive (may be false positive) and increased HCV viral load indicating active disease. Active HCV should be treated sufficiently before inclusion in the study. Below 2 million copies per milliliter (mL) is related to chronic hepatitis C that does not need antiviral therapy.
    • Patients with active hepatitis B or C should be on treatment for at least 4 weeks before inclusion in the trial
  • On sorafenib or other antineoplastic drug therapy within 7 days before inclusion (not accepted until time of progression).
  • Pregnancy or women of childbearing potential require a negative pregnancy test within 28 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: TACE; Transarterial chemoembolization with drug eluted beads or doxorubicin/lipiodol	Drug: DEB; Infusion of DEB or doxorubin/lipiodol through catheter in the hepatic artery; Other Names: doxorubicin
Experimental: SBRT; Stereotactic radiation therapy with risk adapted dose prescription	Radiation: SBRT; High precision radiation therapy to the liver tumor(s)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression (total of local, intra- and extrahepatic)	Modified RECIST	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival	1 year
Response	Modified RESIST	3 months
Local control of treated tumor	Modified RECIST	1 year
Intrahepatic failure	Intrahepatic failure (more than 1 cm away)	1 year
Extrahepatic failure	Modified RECIST	1 year
Treatment related toxicity	Tox CTC Ver 4.0	1 year
Cost-benefit	$ spend on hospitalization and treatment of complications after the treatment	1 year

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: International Atomic Energy Agency

Study record dates

Study Major Dates

• Study Start (Actual): October 26, 2017
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: November 1, 2017
• First Submitted That Met QC Criteria: November 7, 2017
• First Posted (Actual): November 9, 2017

Study Record Updates

• Last Update Posted (Actual): December 2, 2021
• Last Update Submitted That Met QC Criteria: November 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: SBRT; Stereotactic body radiation therapy; TACE; transarterial 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; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antibiotics, Antineoplastic; Doxorubicin
• Other Study ID Numbers: UAarhus HCC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Upon request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No