Combination Chemoembolization and Stereotactic Body Radiation Therapy in Unresectable Hepatocellular Carcinoma

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Recruiting

CT.gov ID

NCT02513199

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.4

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Radiation: SBRT Drug: TACE	Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2014

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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
Active Comparator: TACE alone	Drug: TACE two sessions of standard TACE with ethiodol separated by a 4-week interval. Other Names: Trans-Arterial Chemoembolization

Arm

Intervention/Treatment

Experimental: 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

Active Comparator: TACE alone

Drug: TACE

two sessions of standard TACE with ethiodol separated by a 4-week interval.

Other Names:

Trans-Arterial Chemoembolization

Outcome Measures

Primary Outcome Measures

Response rate [up to 1 year]
Tumor response will be assessed using mRECIST criteria as well diffusion weight imaging (DWI) via Magnetic Resonance Imaging (MRI) surveillance.

Secondary Outcome Measures

Performance status [Baseline and 6 weeks]
Performance status according to ECOG
Time to progression (TTP) [up to 1 year]
the time to progression of the treated lesion
Overall survival (OS) [up to 1 year]
the overall survival as defined from completion of treatment until death
Progression free survival (PFS) [up to 1 year]
the progression free survival as defined from the completion of treatment until disease progression in the treated lesion, liver, or distant metastases

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.