TACE With or Without Radiation Therapy in Treating Patients With Stage A-C Liver Cancer

Trans-Arterial Chemo-Embolization (TACE) vs TACE Plus Stereotactic Body Radio Therapy (SBRT) in the Treatment of Hepatocellular Carcinoma (HCC)

This randomized phase II trial studies how well transarterial chemoembolization (TACE) works compared with TACE plus radiation therapy in treating patients with end stage liver disease, liver tumors, or potential liver transplant candidates. TACE involves reaching up to the blood vessel that feeds the tumor through a catheter placed into the groin vessel. Once the physician has defined the vessel going to the tumor, chemotherapy is infused to the tumor and the vessel is blocked, maintaining the chemotherapy for longer time inside the tumor and stopping the blood flow that feeds the tumor. Stereotactic body radiation therapy (SBRT) is a type of radiation therapy that delivers radiation to the tumor cells but does not harm normal liver cells. It is not yet known whether TACE is more effective with or without SBRT in treating liver tumors.

Study Overview

• Status: Withdrawn
• Conditions: Recurrent Adult Primary Liver Cancer; Adult Primary Hepatocellular Carcinoma; Stage I Adult Primary Liver Cancer; Stage II Adult Primary Liver Cancer; Stage IIIA Adult Primary Liver Cancer
• Intervention / Treatment: Procedure: transarterial chemoembolization; Radiation: stereotactic radiosurgery

Detailed Description

PRIMARY OBJECTIVES:

I. To determine in patients with stage A to C hepatocellular carcinoma, if stereotactic body radiotherapy after TACE enhanced the response rate of hepatocellular carcinoma (HCC) when compared to TACE alone at 3 months.

SECONDARY OBJECTIVES:

I. To determine in patients with stage A to C hepatocellular carcinoma, if TACE plus SBRT can achieve a downstaging rate of >= 30% at 3 and 6 months.

II. To determine the rate of grade 3 or 4 adverse events associated with SBRT for liver tumors.

III. To determine the rate of local progression after SBRT. (Based on Response Evaluation Criteria in Solid Tumors [RECIST] criteria) IV. Number of patients who achieve liver transplantation. V. Overall survival.

OUTLINE: Patients are randomized to 1 of 2 treatment arms after the first loco-regional therapy with TACE.

ARM I: Patients undergo TACE according to institutional standard with doxorubicin-eluting beads.

ARM II: Patients undergo TACE as in Arm I and 3 or 5 fractions of SBRT given at least 48 hours apart over 14 days.

After completion of study treatment, patients are followed up at 1, 3, and 6 months and then periodically thereafter.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HCC is staged as Barcelona A to C
• Treatment with SBRT can occur within 6 weeks of registration
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2

• Patient has

  • Radiographic enhancing liver lesions with early wash out on triple phase CT or MRI or
  • Histological confirmation of HCC as determined by the Liver Tumor Board
• Hemoglobin greater than 10.0 g/dL
• Total bilirubin less than 3.0 mg/dL
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 3 X institutional upper limit of normal
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 X institutional upper limit of normal
• Total aggregate of maximal dimension of liver tumors is =< 8 cm
• Cirrhotic patients Child Pugh class A or B (score =< 7)
• Patient must be determined by the treating physician to be medically eligible for liver transplantation measured by imaging modality (magnetic resonance imaging [MRI]/computed tomography [CT] scan) three months post final treatment
• Absolute neutrophil count >= 1,500/μl
• Platelet count >= 50,000 μl (after transfusion if required)
• Life expectancy > 12 weeks
• Subjects must have the ability to understand and be willing to provide written informed consent
• Women of child-bearing potential must have a negative pregnancy test within 4 weeks to the start of the SBRT treatment
• Women must not be pregnant or nursing
• Sexually active women must agree to use accepted forms of birth control; acceptable options for birth control will be documented in the consent and discussed with the subject prior to enrollment

Exclusion Criteria:

• Patient with previous history of abdominal radiation
• Cirrhotic patients Child Pugh class B with score >= 8
• Prior invasive malignancy other than primary liver malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years
• Evidence of metastatic disease prior to registration
• Evidence of main portal vein thrombosis
• History of known cardiac ischemia or stroke within last 6 months
• Any concurrent medical or psychosocial condition that prohibits a major surgical procedure or immunosuppression that would constitute a contraindication to liver transplantation

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: Arm I (TACE); Patients undergo (transarterial chemoembolization) TACE according to institutional standard with doxorubicin-eluting beads.	Procedure: transarterial chemoembolization; Undergo TACE with doxorubicin-eluting beads; Other Names: TACE
Experimental: Arm II (TACE+SBRT); Patients undergo transarterial chemoembolization (TACE) as in Arm I and 3 or 5 fractions of stereotactic radiosurgery (SBRT) given at least 48 hours apart over 14 days.	Procedure: transarterial chemoembolization; Undergo TACE with doxorubicin-eluting beads; Other Names: TACE; Radiation: stereotactic radiosurgery; Undergo SBRT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage change in gross tumor volume (GTV)	Percentage of tumor response as defined as change in longest diameter of tumor compared to original tumor length	Baseline to 3 months
Difference in mean gross tumor volume (GTV), assessed using the RECIST method	Difference in mean GTV from T0M and T3M calculated by a student t-test	Baseline to 3 months
Difference in tumor grade	Difference in the grade of tumor (as defined by the RECIST criteria) at T0 and T3 calculated using Chi-square tests.	Baseline to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of downstaging	Rate of downstaging of stage A to C Hepatocellular Carcinoma using TACE plus SBRT when compared to TACE at 3 and 6 months.	Up to 6 months
Grade 3 or 4 adverse events associated with liver tumors	Number of grade 3 or 4 adverse events associated with SBRT for liver tumors, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events	Up to 1 year
Rate of local progression, based on RECIST criteria	Rate of local disease progression when progression is defined as an estimated increase of > 20% in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since the treatment started or the appearance of one or more new lesions.	Up to 6 months
Liver transplant achievement	Number of patients who achieve liver transplantation	Up to 6 months
Survival rate	The number of days from the first day of treatment on study until death of any cause	1 year

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Juan Sanabria, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): November 1, 2014

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): December 2, 2014
• Last Update Submitted That Met QC Criteria: December 1, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• 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; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: CASE2212; P30CA043703 (U.S. NIH Grant/Contract); NCI-2014-00246 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CASE 2212 (Other Identifier: Case Comprehensive Cancer Center)