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

Phase 2

Withdrawn

• Conditions: Stage II Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Stage I Adult Primary Liver Cancer; Stage IIIA Adult Primary Liver Cancer; Adult Primary Hepatocellular Carcinoma
• Interventions: Procedure: transarterial chemoembolization; Radiation: stereotactic radiosurgery

• Registration Number: NCT02070419
• Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary

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.

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 Timeline

• Study First Submitted: 2014-02-21
• Study First Submitted QC: 2014-02-24
• Study First Posted: 2014-02-25
• Study Start: 2014-04
• Primary Completion: 2014-11
• Study Completion: 2014-11
• Status Verified: 2014-12
• Last Update Submitted: 2014-12-01
• Last Update Posted: 2014-12-02

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm II (TACE+SBRT)	transarterial chemoembolization	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.
Arm I (TACE)	transarterial chemoembolization	Patients undergo (transarterial chemoembolization) TACE according to institutional standard with doxorubicin-eluting beads.
Arm II (TACE+SBRT)	stereotactic radiosurgery	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Rate of local progression, based on RECIST criteria	Up to 6 months	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.
Rate of downstaging	Up to 6 months	Rate of downstaging of stage A to C Hepatocellular Carcinoma using TACE plus SBRT when compared to TACE at 3 and 6 months.
Liver transplant achievement	Up to 6 months	Number of patients who achieve liver transplantation
Grade 3 or 4 adverse events associated with liver tumors	Up to 1 year	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
Survival rate	1 year	The number of days from the first day of treatment on study until death of any cause