Back to resultsA Pilot Study to Assess Theragnostically Planned Liver Radiation to Optimize Radiation Therapy
Primary Purpose
Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Hepatobiliary Iminodiacetic Acid (HIDA) scan
Sponsored by
About this trial
This is an interventional diagnostic trial for Liver Cancer focused on measuring Radiation Treatment
Eligibility Criteria
Inclusion Criteria
- Subjects must be ≥ 18 years of age at the time of signing informed consent
- Diagnosis of primary liver malignancy (including hepatocellular carcinoma [HCC] or cholangiocarcinoma) or liver metastasis from any primary solid tumor site by characteristic imaging findings on CT or MRI, clinical presentation, and/or pathologic confirmation of diagnosis.
- Subjects with other current or prior malignancies are eligible for this study.
Patients with liver metastases must have at least one of the following clinical factors that may affect liver function:
- History of liver resection (at any time)
- History of cirrhosis (any cause), fatty liver disease, or hepatic insufficiency due to any cause
- Prior radiation to the upper abdomen including radioembolization
- ECOG (Zubrod) Performance Status 0-2.
- Subjects must have a Child-Turcotte-Pugh (CTP) score ≤ 7 to be eligible.
- Patients who have been previously treated with non-SBRT liver directed therapies may be enrolled on study. At least 3 months must have elapsed between the most recent liver-directed therapy and study entry.
- Ability to provide written informed consent and HIPAA authorization
- Subjects with an allergy to contrast agents may be enrolled at the treating physician's discretion with appropriate pre-treatment and symptom management.
Exclusion Criteria
- Subjects who are pregnant or planning to become pregnant during the study. Women of child bearing potential must have a negative pregnancy test
- Subjects must not have received chemotherapy within 2 weeks of planned 1st day of RT.
- No more than 3 lesions may be treated. The maximum sum of the diameter(s) of the lesion(s) must be ≤6 cm
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (or infections requiring systemic antibiotic treatment), active upper GI ulceration or hemorrhage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would in the opinion of the investigator limit compliance with study requirements
Sites / Locations
- Indiana University Melvin & Bren Simon Cancer Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Theragnostic SBRT Planning
Standard SBRT Planning
Arm Description
The theragnostic SBRT plan using the HIDA scan was chosen as the plan that reduced the dose of radiation to functional liver without compromising target coverage or tumor control.
The standard SBRT plan was chosen as the plan that reduced the dose of radiation to functional liver without compromising target coverage or tumor control.
Outcomes
Primary Outcome Measures
Difference in Functional Reserve of Liver Between Theragnostic SBRT Planning and Standard SBRT Planning
The functional reserve of the liver for both standard SBRT planning and theragnostic SBRT planning will be calculated for each patient regardless of which plan was ultimately chosen.
Function reserve of the liver = (number of counts outside 15 Gy isodose line / total number of counts within the liver) * global liver function; where global liver function is the rate of liver uptake (%/min) between 150 to 300 seconds normalized to body surface area (m^2) using the Du Bois method. The difference in functional reserve between the theragnostic plan and the standard plan was calculated for each patient.
Secondary Outcome Measures
Percentage of Participants for Whom Theragnostically Planned Radiation is Chosen for the Radiation Treatment Plan
The percentage of participants for whom theragnostically planned radiation is chosen for the radiation treatment plan over the standard plan will be calculated along with the corresponding exact 95% Binomial confidence interval.
Duration of Local Control
Duration of local control was assessed by calculating the time from on study date to date of local failure. Patients who did not experience local failure were censored at their last evaluation date. Local failure (progressive disease at primary diagnosis site) was evaluated using RECIST v1.1 criteria:
Complete response: Disappearance of all target lesions; Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter; Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Progression Free Survival
Progression free survival was defined as the time from on study date to date of recurrence of any type or death from any cause. Patients who did not experience recurrence or death were censored at their last evaluation date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Overall Survival
Overall survival was defined as the time from on study date to death due to any cause. Patients who remained alive were censored at their last known alive date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time to Transplant
Time to transplant was defined as the time from on study date to the date of transplant. Patients who did not receive transplant were censored at their off study date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time to Distant Liver Failure
Time to distant liver failure was defined as the time from on study date to the date of distant liver failure. Patients who did not experience distant liver failure were censored at their date of last evaluation. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time Until Salvage Treatment
Time until salvage treatment was defined as the time from on study date to the start date of salvage treatment. Patients who did not receive salvage treatment were censored at their off study date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Number of Patients With Treatment-Related Adverse Events Grade 3 or Above
Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event with grade 3 or greater using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Change in MELD Score
Model for end-stage liver disease (MELD) score measures the severity of liver dysfunction. MELD scores range from 6 to 40 and are based on lab tests including serum creatinine, total bilirubin, and INR. The higher the number, the worse the liver function.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03338062
Brief Title
A Pilot Study to Assess Theragnostically Planned Liver Radiation to Optimize Radiation Therapy
Official Title
A Pilot Study to Assess Theragnostically Planned Liver Radiation With Functional DVH Analysis to Optimize Individualized Radiation Therapy
Study Type
Interventional
2. Study Status
Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
June 13, 2017 (Actual)
Primary Completion Date
September 2, 2019 (Actual)
Study Completion Date
September 2, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare radiation treatment plans that are designed for patients with liver cancer. One treatment plan will be created using routine procedures and scans normally performed for radiation treatment planning. The other treatment plan will be created using routine procedures with the addition of two imaging scans; a HIDA (Hepatobiliary Iminodiacetic Acid) scan and an MRI (Magnetic Resonance Imaging) scan. This study will evaluate if adding these imaging scans to treatment planning can reduce the amount of radiation to healthy liver tissue during treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cancer, Hepatocellular Carcinoma, Cholangiocarcinoma
Keywords
Radiation Treatment
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Theragnostic SBRT Planning
Arm Type
Experimental
Arm Description
The theragnostic SBRT plan using the HIDA scan was chosen as the plan that reduced the dose of radiation to functional liver without compromising target coverage or tumor control.
Arm Title
Standard SBRT Planning
Arm Type
No Intervention
Arm Description
The standard SBRT plan was chosen as the plan that reduced the dose of radiation to functional liver without compromising target coverage or tumor control.
Intervention Type
Diagnostic Test
Intervention Name(s)
Hepatobiliary Iminodiacetic Acid (HIDA) scan
Intervention Description
HIDA scan was used as the planning scan for SBRT.
Primary Outcome Measure Information:
Title
Difference in Functional Reserve of Liver Between Theragnostic SBRT Planning and Standard SBRT Planning
Description
The functional reserve of the liver for both standard SBRT planning and theragnostic SBRT planning will be calculated for each patient regardless of which plan was ultimately chosen.
Function reserve of the liver = (number of counts outside 15 Gy isodose line / total number of counts within the liver) * global liver function; where global liver function is the rate of liver uptake (%/min) between 150 to 300 seconds normalized to body surface area (m^2) using the Du Bois method. The difference in functional reserve between the theragnostic plan and the standard plan was calculated for each patient.
Time Frame
Day -1 of Radiation Treatment
Secondary Outcome Measure Information:
Title
Percentage of Participants for Whom Theragnostically Planned Radiation is Chosen for the Radiation Treatment Plan
Description
The percentage of participants for whom theragnostically planned radiation is chosen for the radiation treatment plan over the standard plan will be calculated along with the corresponding exact 95% Binomial confidence interval.
Time Frame
Day -1 of Radiation Treatment
Title
Duration of Local Control
Description
Duration of local control was assessed by calculating the time from on study date to date of local failure. Patients who did not experience local failure were censored at their last evaluation date. Local failure (progressive disease at primary diagnosis site) was evaluated using RECIST v1.1 criteria:
Complete response: Disappearance of all target lesions; Partial response: At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter; Stable Disease: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time Frame
Up to 15 months
Title
Progression Free Survival
Description
Progression free survival was defined as the time from on study date to date of recurrence of any type or death from any cause. Patients who did not experience recurrence or death were censored at their last evaluation date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time Frame
Up to 15 months
Title
Overall Survival
Description
Overall survival was defined as the time from on study date to death due to any cause. Patients who remained alive were censored at their last known alive date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time Frame
Up to 3 years
Title
Time to Transplant
Description
Time to transplant was defined as the time from on study date to the date of transplant. Patients who did not receive transplant were censored at their off study date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time Frame
Up to 15 months
Title
Time to Distant Liver Failure
Description
Time to distant liver failure was defined as the time from on study date to the date of distant liver failure. Patients who did not experience distant liver failure were censored at their date of last evaluation. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time Frame
Up to 15 months
Title
Time Until Salvage Treatment
Description
Time until salvage treatment was defined as the time from on study date to the start date of salvage treatment. Patients who did not receive salvage treatment were censored at their off study date. The Kaplan-Meier method was used to determine the median and 95% confidence interval.
Time Frame
Up to 15 months
Title
Number of Patients With Treatment-Related Adverse Events Grade 3 or Above
Description
Number of unique patients who had a treatment-related (possible, probable, or definite) adverse event with grade 3 or greater using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Time Frame
Every 15 days for approximately 6 months
Title
Change in MELD Score
Description
Model for end-stage liver disease (MELD) score measures the severity of liver dysfunction. MELD scores range from 6 to 40 and are based on lab tests including serum creatinine, total bilirubin, and INR. The higher the number, the worse the liver function.
Time Frame
Up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Subjects must be ≥ 18 years of age at the time of signing informed consent
Diagnosis of primary liver malignancy (including hepatocellular carcinoma [HCC] or cholangiocarcinoma) or liver metastasis from any primary solid tumor site by characteristic imaging findings on CT or MRI, clinical presentation, and/or pathologic confirmation of diagnosis.
Subjects with other current or prior malignancies are eligible for this study.
Patients with liver metastases must have at least one of the following clinical factors that may affect liver function:
History of liver resection (at any time)
History of cirrhosis (any cause), fatty liver disease, or hepatic insufficiency due to any cause
Prior radiation to the upper abdomen including radioembolization
ECOG (Zubrod) Performance Status 0-2.
Subjects must have a Child-Turcotte-Pugh (CTP) score ≤ 7 to be eligible.
Patients who have been previously treated with non-SBRT liver directed therapies may be enrolled on study. At least 3 months must have elapsed between the most recent liver-directed therapy and study entry.
Ability to provide written informed consent and HIPAA authorization
Subjects with an allergy to contrast agents may be enrolled at the treating physician's discretion with appropriate pre-treatment and symptom management.
Exclusion Criteria
Subjects who are pregnant or planning to become pregnant during the study. Women of child bearing potential must have a negative pregnancy test
Subjects must not have received chemotherapy within 2 weeks of planned 1st day of RT.
No more than 3 lesions may be treated. The maximum sum of the diameter(s) of the lesion(s) must be ≤6 cm
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (or infections requiring systemic antibiotic treatment), active upper GI ulceration or hemorrhage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would in the opinion of the investigator limit compliance with study requirements
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryan M Rhome, MD
Organizational Affiliation
Indiana University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Melvin & Bren Simon Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Pilot Study to Assess Theragnostically Planned Liver Radiation to Optimize Radiation Therapy
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