Combination Chemoembolization and Stereotactic Body Radiation Therapy in Unresectable Hepatocellular Carcinoma

May 21, 2023 updated by: Michael Buckstein, Icahn School of Medicine at Mount Sinai

Assessment of Response of Unresectable Hepatocellular Carcinoma to Combination Chemoembolization and Stereotactic Body Radiation Therapy

The purpose of this study is to develop better ways to treat liver cancer, known as hepatocellular carcinoma or HCC, while it is still in the liver. Many treatments exist to treat tumors in the liver when they are small but after they grow past a certain size, local therapies such as surgery, Trans-Arterial Chemo Embolization (TACE), or Radiofrequency Ablation (RFA) are not effective. The purpose of this study to test the combination of two known treatments - TACE and Stereotactic Body Radiation Therapy (SBRT) - to be used together to treat larger or difficult to access liver tumors. Each treatment has been shown to work well but has limitations. The study will combine the treatments in an organized sequence and monitor closely how effective this combination controls tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Hepatocellular carcinoma (HCC) is the third ranked cause of global cancer mortality. There is an increasing incidence of HCC in the United States over the last twenty years, largely due to the Hepatitis C epidemic but increasingly related as well to nonalcoholic fatty liver disease.

This is a non-randomized pilot study to assess the objective response rate and durability of response of combination Trans-Arterial Chemoembolization (TACE) with immediate stereotactic body radiation therapy (SBRT) in the treatment of unresectable hepatocellular carcinoma (HCC). Eligible patients will be selected based on having a lesion greater than 3 cm which would make them ineligible for other local therapies such as TACE and thermal ablation (TA). Eligible, consented, and registered patients will be treated with two sessions of standard TACE with ethiodol separated by a 4-week interval. After ensuring adequate return to baseline liver function, the patients will then be treated with SBRT to the targeted lesion to 30-45 Gy in 5 fractions. Tumor response will be assessed using mRECIST criteria as well diffusion weight imaging (DWI) via Magnetic Resonance Imaging (MRI) surveillance. In addition, tolerability and toxicity will be recorded via CTCAE v. 4.0. The essential hypothesis of this study is that combination TACE and SBRT for > 3 cm HCC will produce higher response rates and durable control compared to TACE alone.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Icahn School of Medicine at Mount Sinai

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must be diagnosed with HCC either pathologically or by the American Association for the Study of Liver Diseases (AASLD) radiographic criteria (Bruix Hepatology 2011). The criteria specifies CT or MRI intense arterial uptake followed by "washout" of contrast in the venous-delayed phases. Any atypical lesions must be confirmed by biopsy.
  • A single liver lesion with tumor size ≥ 3 cm as defined as maximal diameter in the axial dimension on MRI. Included in the measurement are both enhancing and non-enhancing components of the lesion.
  • Maximum tumor size of 7 cm as defined as maximal diameter in the axial dimension on MRI.
  • Age ≥ 18 years
  • Child-Pugh class A or B7 without ascites
  • ECOG score 0
  • No prior treatment of current HCC. However, recurrent HCC after resection may be included.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Pregnancy which will be assessed via pregnancy test prior to TACE and repeated prior to SBRT.
  • Metastatic disease outside of the liver
  • Vascular invasion as evidenced by vessel occlusion or radiographic evidence of tumor thrombus.
  • Contraindications to MRI, including claustrophobia, metallic implants, and pacemakers
  • Tumor for which adequate radiation dosage cannot be safely delivered (see dose constraints below)
  • Prior therapeutic radiation therapy to the abdomen and/or lower thorax as defined as below the carina to the pelvic inlet.
  • Inability to provide informed consent based on persistent lack of understanding, inability to find adequate translation, impaired mental status such as mental retardation, drug induced, or traumatic brain injury.
  • Multiple liver tumors making the patient a BCLC Stage B
  • Prior treatment, except for surgical resection, to the lesion being targeted in the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Participants with HCC
Participants with HCC with a lesion greater than 3 cm treated with TACE/SBRT combination
Radiation: SBRT
Radiation is to be delivered to 30-45 Gy in 5 fractions. 40 Gy in 5 fractions will be utilized, unless dose constraints preclude it. Treatment will optimally be delivered every other day with no more than 3 fractions per week. The ideal treatment team will be less than 15 total days.
Other Names:
  • Stereotactic Body Radiation Therapy
Drug: TACE
two sessions of standard TACE with ethiodol separated by a 4-week interval.
Other Names:
  • Trans-Arterial Chemoembolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Objective Response Rate
Time Frame: up to 72 months

Tumor response will be assessed using mRECIST criteria as well diffusion weight imaging (DWI) via Magnetic Resonance Imaging (MRI) surveillance.

  • Complete response (CR): Disappearance of all target lesions
  • Partial response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD
  • Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started
  • Progressive disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions
up to 72 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to CR
Time Frame: up to 72 months
Time to Complete Remission (CR)
up to 72 months
Time to Progression (TTP)
Time Frame: up to 80 months
The time to progression of the treated lesion. Median TTP, as defined as progression events (not including death), was not reached because 50% of events were not achieved. Because a sufficient number of progression events did not happen at the time of study censure, a median could not be reported. Therefore, mean is reported which can be reported irrespective of events.
up to 80 months
Number of Participants With Overall Survival (OS)
Time Frame: 2 years
The overall survival as defined from completion of treatment until death
2 years
Progression Free Survival (PFS)
Time Frame: up to 72 months
Progression-free survival (PFS), defined as time between enrollment and tumor progression assessed by mRECIST or death, local control (LC), and toxic effects. LC was defined as either absence of radiographic progression or a secondary intervention (ie, surgery or TACE) made to the index lesion due to a perceived incomplete treatment response.
up to 72 months
Change in Child-Turcotte-Pugh (CTP) Score
Time Frame: 3 months

Overall rate of toxic effects as measured by change in Child-Turcotte-Pugh (CTP) score at 3 months as compared to baseline.

The Child-Turcotte-Pugh (CTP) is a scale that assesses a patients baseline liver function and can help predict morbidity and mortality based on that score.

Class A - 5 to 6 points, least severe liver disease, one- to five-year survival rate: 95 percent

Class B - 7 to 9 points, moderately severe liver disease, one- to five-year survival rate: 75 percent

Class C - 10 to 15 points, most severe liver disease, one- to five-year survival rate: 50 percent

Higher scores correlate with more general mortality.
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Investigators

  • Principal Investigator: Michael Buckstein, MD, PhD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Actual)

January 1, 2022

Study Completion (Actual)

January 1, 2022

Study Registration Dates

First Submitted

July 30, 2015

First Submitted That Met QC Criteria

July 30, 2015

First Posted (Estimated)

July 31, 2015

Study Record Updates

Last Update Posted (Estimated)

June 16, 2023

Last Update Submitted That Met QC Criteria

May 21, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GCO 14-1671

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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