Back to resultsTACE With or Without Radiation Therapy in Treating Patients With Stage A-C Liver Cancer
Primary Purpose
Adult Primary Hepatocellular Carcinoma, Recurrent Adult Primary Liver Cancer, Stage I Adult Primary Liver Cancer
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
transarterial chemoembolization
stereotactic radiosurgery
Sponsored by
About this trial
This is an interventional treatment trial for Adult Primary Hepatocellular Carcinoma
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Arm I (TACE)
Arm II (TACE+SBRT)
Arm Description
Patients undergo (transarterial chemoembolization) TACE according to institutional standard with doxorubicin-eluting beads.
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.
Outcomes
Primary Outcome Measures
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
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
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.
Secondary Outcome Measures
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.
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
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.
Liver transplant achievement
Number of patients who achieve liver transplantation
Survival rate
The number of days from the first day of treatment on study until death of any cause
Full Information
NCT ID
NCT02070419
First Posted
February 21, 2014
Last Updated
December 1, 2014
Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT02070419
Brief Title
TACE With or Without Radiation Therapy in Treating Patients With Stage A-C Liver Cancer
Official Title
Trans-Arterial Chemo-Embolization (TACE) vs TACE Plus Stereotactic Body Radio Therapy (SBRT) in the Treatment of Hepatocellular Carcinoma (HCC)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Withdrawn
Why Stopped
Principal Investigator left institution
Study Start Date
April 2014 (undefined)
Primary Completion Date
November 2014 (Actual)
Study Completion Date
November 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Case Comprehensive Cancer Center
Collaborators
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adult Primary Hepatocellular Carcinoma, Recurrent Adult Primary Liver Cancer, Stage I Adult Primary Liver Cancer, Stage II Adult Primary Liver Cancer, Stage IIIA Adult Primary Liver Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm I (TACE)
Arm Type
Active Comparator
Arm Description
Patients undergo (transarterial chemoembolization) TACE according to institutional standard with doxorubicin-eluting beads.
Arm Title
Arm II (TACE+SBRT)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
transarterial chemoembolization
Other Intervention Name(s)
TACE
Intervention Description
Undergo TACE with doxorubicin-eluting beads
Intervention Type
Radiation
Intervention Name(s)
stereotactic radiosurgery
Intervention Description
Undergo SBRT
Primary Outcome Measure Information:
Title
Percentage change in gross tumor volume (GTV)
Description
Percentage of tumor response as defined as change in longest diameter of tumor compared to original tumor length
Time Frame
Baseline to 3 months
Title
Difference in mean gross tumor volume (GTV), assessed using the RECIST method
Description
Difference in mean GTV from T0M and T3M calculated by a student t-test
Time Frame
Baseline to 3 months
Title
Difference in tumor grade
Description
Difference in the grade of tumor (as defined by the RECIST criteria) at T0 and T3 calculated using Chi-square tests.
Time Frame
Baseline to 3 months
Secondary Outcome Measure Information:
Title
Rate of downstaging
Description
Rate of downstaging of stage A to C Hepatocellular Carcinoma using TACE plus SBRT when compared to TACE at 3 and 6 months.
Time Frame
Up to 6 months
Title
Grade 3 or 4 adverse events associated with liver tumors
Description
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
Time Frame
Up to 1 year
Title
Rate of local progression, based on RECIST criteria
Description
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.
Time Frame
Up to 6 months
Title
Liver transplant achievement
Description
Number of patients who achieve liver transplantation
Time Frame
Up to 6 months
Title
Survival rate
Description
The number of days from the first day of treatment on study until death of any cause
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan Sanabria
Organizational Affiliation
Case Comprehensive Cancer Center
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
TACE With or Without Radiation Therapy in Treating Patients With Stage A-C Liver Cancer
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