SBRT for Hepatocellular Carcinoma Patients With Partial Response to TACE
Primary Purpose
Carcinoma, Hepatocellular
Status
Active
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
SBRT
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Hepatocellular focused on measuring Carcinoma, Hepatocellular, SBRT
Eligibility Criteria
Inclusion Criteria:
- HCC diagnosis according to the American Association for the Study of Liver Diseases (AASLD) 2010 criteria
- Tumor Stage
- liver only disease
- tumor thrombus at segment is allowed
- no extra hepatic metastases
- tumor encompassing less than 50% of hepatic volume
- previous treatment with Transarterial Chemo Embolization (TACE) - patient must have performed at least 2 sessions of TACE and have signs of viable tumor in CT or MRI performed 30-40 days after last TACE
- presence of measurable lesion (at least one lesion that can be measured equal or more than 1 cm in CT or MRI).
- Maximum lesion size of 10 cm.
- Liver residual volume equal or more than 700cc or 40% of total liver volume
- Child-Pugh A or absence of hepatic cirrhosis
- absence of encephalopathy or ascitis on clinical exam
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Lab exams:
- hemoglobin > or equal 8 mg/dl
- neutrophils > or equal 1.200/mm³
- platelets > or equal 45.000/mm³
- alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 6 times the upper normal limit
- bilirubin equal or < 2 mg/dl
- international normalized ratio (INR) < 1.7
- serum creatinine equal or < 1.5 times the upper normal limit or creatinine clearance > or equal 60 ml/min
- Albumin >2.8 mg/dl
- not being pregnant - a negative pregnancy test is required (for women). Patients in fertile age should use a contraceptive method during treatment and 4 months after.
Exclusion Criteria:
- Patients with more than 5 discrete lesions in the liver
- Main or common biliary duct invasion
- Patients with main portal vein tumor thrombus or more than 2 portal branch thrombus
- Patients in systemic treatment (sorafenib, chemotherapy). There should be an interval of at least 4 weeks between any medication for treatment of HCC and the current study treatment
- Previous radiation to upper abdomen
- Patients with other malignant neoplasms or previous malignant neoplasms will be accepted in the study if HCC prognosis is worse
- Patients with ischemic myocardial infarction within the last 6 months
- Patients with large esophageal varices with red color sign or bleeding within the last 3 months
- Patients with symptoms of colitis, enteritis, esophagitis, fistula, ileus, necrosis, stenosis or ulcer
- Patients with severe anorexy, constipation, dehydration, diarrhea or vomiting
- Patients unable to understand and sign written informed consent
Sites / Locations
- Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da USP
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
SBRT
Arm Description
SBRT according to the intervention description
Outcomes
Primary Outcome Measures
Local Progression Free Survival
Local Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.
Local Progression Free Survival will be defined as increase of 20% in the sum of all diameters of the treated lesions.
Time-to-event will be counted from the initiation of SBRT
Secondary Outcome Measures
Distant Progression Free Survival
Distant Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.
Distant Progression Free Survival will be defined as the appearance of a new hepatic lesion, tumoral thrombus or distant metastases.
Time-to-event will be counted from the initiation of SBRT
Toxicity
Toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Toxicity will be evaluated weekly during treatment, monthly in the first 3 months after treatment and every 3 months after.
Acute Toxicity will be defined as toxicity that develops within the first 3 months after initiation treatment.
Chronic Toxicity will be defined as toxicity that develops after 3 months of initiation of treatment.
Overall Survival
Time-to-event will be counted from the initiation of SBRT
Full Information
NCT ID
NCT02221778
First Posted
August 19, 2014
Last Updated
December 15, 2021
Sponsor
University of Sao Paulo
1. Study Identification
Unique Protocol Identification Number
NCT02221778
Brief Title
SBRT for Hepatocellular Carcinoma Patients With Partial Response to TACE
Official Title
Stereotactic Body Radiation Therapy for Hepatocellular Carcinoma Patients With Partial Response to Transarterial Chemoembolization
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Active, not recruiting
Study Start Date
August 2014 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Sao Paulo
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This is a pilot study where patients with Hepatocellular Carcinoma (HCC) that have failed Transarterial Chemoembolization (TACE) will be treated with Stereotactic Body Radiation Therapy (SBRT). The focus of the study will be to evaluate safety and efficacy in our population of patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Hepatocellular
Keywords
Carcinoma, Hepatocellular, SBRT
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
SBRT
Arm Type
Experimental
Arm Description
SBRT according to the intervention description
Intervention Type
Radiation
Intervention Name(s)
SBRT
Intervention Description
SBRT will be prescribed according to the Radiation Therapy Oncology Group (RTOG) 1112 protocol using Mean Liver Dose (MLD) as parameter. MLD will be calculated using Liver minus Gross Tumor Volume (GTV). Prescription dose will follow the scheme below:
Prescription dose(Gy) / (MLD) (Gy)
50 / 13
45 / 15
40 / 15
35 / 15.5
30 / 16
27.5 / 17
If the dose constraints cannot be met, prescription will be according to the level immediately bellow.
Treatment will be delivered in 5 fractions in consecutive working days
Primary Outcome Measure Information:
Title
Local Progression Free Survival
Description
Local Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.
Local Progression Free Survival will be defined as increase of 20% in the sum of all diameters of the treated lesions.
Time-to-event will be counted from the initiation of SBRT
Time Frame
5 years
Secondary Outcome Measure Information:
Title
Distant Progression Free Survival
Description
Distant Progression Free Survival will be measured on triphasic Computerized Tomography (CT) or Magnetic Resonance Imaging (MRI) when clinically indicated.
The exam will be performed every 3 months after the end of treatment. The tumor response will be measured according to the modified RECIST (mRECIST) directed to the HCC study.
Distant Progression Free Survival will be defined as the appearance of a new hepatic lesion, tumoral thrombus or distant metastases.
Time-to-event will be counted from the initiation of SBRT
Time Frame
5 years
Title
Toxicity
Description
Toxicity will be evaluated according to the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Toxicity will be evaluated weekly during treatment, monthly in the first 3 months after treatment and every 3 months after.
Acute Toxicity will be defined as toxicity that develops within the first 3 months after initiation treatment.
Chronic Toxicity will be defined as toxicity that develops after 3 months of initiation of treatment.
Time Frame
5 years
Title
Overall Survival
Description
Time-to-event will be counted from the initiation of SBRT
Time Frame
5 years
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
HCC diagnosis according to the American Association for the Study of Liver Diseases (AASLD) 2010 criteria
Tumor Stage
liver only disease
tumor thrombus at segment is allowed
no extra hepatic metastases
tumor encompassing less than 50% of hepatic volume
previous treatment with Transarterial Chemo Embolization (TACE) - patient must have performed at least 2 sessions of TACE and have signs of viable tumor in CT or MRI performed 30-40 days after last TACE
presence of measurable lesion (at least one lesion that can be measured equal or more than 1 cm in CT or MRI).
Maximum lesion size of 10 cm.
Liver residual volume equal or more than 700cc or 40% of total liver volume
Child-Pugh A or absence of hepatic cirrhosis
absence of encephalopathy or ascitis on clinical exam
Eastern Cooperative Oncology Group (ECOG) performance status 0-1
Lab exams:
hemoglobin > or equal 8 mg/dl
neutrophils > or equal 1.200/mm³
platelets > or equal 45.000/mm³
alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than 6 times the upper normal limit
bilirubin equal or < 2 mg/dl
international normalized ratio (INR) < 1.7
serum creatinine equal or < 1.5 times the upper normal limit or creatinine clearance > or equal 60 ml/min
Albumin >2.8 mg/dl
not being pregnant - a negative pregnancy test is required (for women). Patients in fertile age should use a contraceptive method during treatment and 4 months after.
Exclusion Criteria:
Patients with more than 5 discrete lesions in the liver
Main or common biliary duct invasion
Patients with main portal vein tumor thrombus or more than 2 portal branch thrombus
Patients in systemic treatment (sorafenib, chemotherapy). There should be an interval of at least 4 weeks between any medication for treatment of HCC and the current study treatment
Previous radiation to upper abdomen
Patients with other malignant neoplasms or previous malignant neoplasms will be accepted in the study if HCC prognosis is worse
Patients with ischemic myocardial infarction within the last 6 months
Patients with large esophageal varices with red color sign or bleeding within the last 3 months
Patients with symptoms of colitis, enteritis, esophagitis, fistula, ileus, necrosis, stenosis or ulcer
Patients with severe anorexy, constipation, dehydration, diarrhea or vomiting
Patients unable to understand and sign written informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Flair J Carrilho, MD, PhD
Organizational Affiliation
University of Sao Paulo
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Andre T Chen, MD, PhD
Organizational Affiliation
University of Sao Paulo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto do Cancer do Estado de Sao Paulo, Hospital das Clinicas da Faculdade de Medicina da USP
City
Sao Paulo
ZIP/Postal Code
01246000
Country
Brazil
12. IPD Sharing Statement
Citations:
PubMed Identifier
34211773
Citation
Chen ATC, Payao F, Chagas AL, De Souza Melo Alencar RS, Tani CM, da Conceicao Vasconcelos KGM, de Souza Rocha M, de Andrade Carvalho H, Hoff PMG, Carrilho FJ. Feasibility of SBRT for hepatocellular carcinoma in Brazil - a prospective pilot study. Rep Pract Oncol Radiother. 2021 Apr 14;26(2):226-236. doi: 10.5603/RPOR.a2021.0035. eCollection 2021.
Results Reference
derived
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SBRT for Hepatocellular Carcinoma Patients With Partial Response to TACE
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