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Combination Chemoembolization and Stereotactic Body Radiation Therapy in Unresectable Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
SBRT
TACE
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring Hepatocellular Carcinoma, Trans-Arterial Chemoembolization, Stereotactic Body Radiation Therapy, HCC, TACE, SBRT

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Participants with HCC

Arm Description

Participants with HCC with a lesion greater than 3 cm treated with TACE/SBRT combination

Outcomes

Primary Outcome Measures

Number of Participants With Objective Response Rate
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

Secondary Outcome Measures

Time to CR
Time to Complete Remission (CR)
Time to Progression (TTP)
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.
Number of Participants With Overall Survival (OS)
The overall survival as defined from completion of treatment until death
Progression Free Survival (PFS)
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.
Change in Child-Turcotte-Pugh (CTP) Score
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.

Full Information

First Posted
July 30, 2015
Last Updated
May 21, 2023
Sponsor
Icahn School of Medicine at Mount Sinai
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1. Study Identification

Unique Protocol Identification Number
NCT02513199
Brief Title
Combination Chemoembolization and Stereotactic Body Radiation Therapy in Unresectable Hepatocellular Carcinoma
Official Title
Assessment of Response of Unresectable Hepatocellular Carcinoma to Combination Chemoembolization and Stereotactic Body Radiation Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
November 2014 (undefined)
Primary Completion Date
January 1, 2022 (Actual)
Study Completion Date
January 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Icahn School of Medicine at Mount Sinai

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Carcinoma
Keywords
Hepatocellular Carcinoma, Trans-Arterial Chemoembolization, Stereotactic Body Radiation Therapy, HCC, TACE, SBRT

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Participants with HCC
Arm Type
Experimental
Arm Description
Participants with HCC with a lesion greater than 3 cm treated with TACE/SBRT combination
Intervention Type
Radiation
Intervention Name(s)
SBRT
Other Intervention Name(s)
Stereotactic Body Radiation Therapy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
TACE
Other Intervention Name(s)
Trans-Arterial Chemoembolization
Intervention Description
two sessions of standard TACE with ethiodol separated by a 4-week interval.
Primary Outcome Measure Information:
Title
Number of Participants With Objective Response Rate
Description
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
Time Frame
up to 72 months
Secondary Outcome Measure Information:
Title
Time to CR
Description
Time to Complete Remission (CR)
Time Frame
up to 72 months
Title
Time to Progression (TTP)
Description
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.
Time Frame
up to 80 months
Title
Number of Participants With Overall Survival (OS)
Description
The overall survival as defined from completion of treatment until death
Time Frame
2 years
Title
Progression Free Survival (PFS)
Description
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.
Time Frame
up to 72 months
Title
Change in Child-Turcotte-Pugh (CTP) Score
Description
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.
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Buckstein, MD, PhD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
35643250
Citation
Buckstein M, Kim E, Ozbek U, Tabrizian P, Gunasekaran G, Facciuto M, Rosenzweig K, Llovet JM, Schwartz M. Combination Transarterial Chemoembolization and Stereotactic Body Radiation Therapy for Unresectable Single Large Hepatocellular Carcinoma: Results From a Prospective Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2022 Oct 1;114(2):221-230. doi: 10.1016/j.ijrobp.2022.05.021. Epub 2022 May 26.
Results Reference
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Combination Chemoembolization and Stereotactic Body Radiation Therapy in Unresectable Hepatocellular Carcinoma

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