Combination Chemoembolization and Stereotactic Body Radiation Therapy in Unresectable Hepatocellular Carcinoma

Phase 2

Completed

Conditions: Hepatocellular Carcinoma

Interventions: Radiation: SBRT
Drug: TACE

Registration Number: NCT02513199

Lead Sponsor: Icahn School of Medicine at Mount Sinai

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 32

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of Participants With Objective Response Rate	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

Secondary Outcome Measures

Name	Time	Method
Time to CR	up to 72 months	Time to Complete Remission (CR)
Time to Progression (TTP)	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.
Number of Participants With Overall Survival (OS)	2 years	The overall survival as defined from completion of treatment until death
Progression Free Survival (PFS)	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.
Change in Child-Turcotte-Pugh (CTP) Score	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.