Trial Outcomes & Findings for A Pilot Study to Assess Theragnostically Planned Liver Radiation to Optimize Radiation Therapy (NCT NCT03338062)

Last Updated: 2021-02-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

15 participants

Primary outcome timeframe

Day -1 of Radiation Treatment

Results posted on

2021-02-26

Participant Flow

Participant milestones

Participant milestones
Measure	Theragnostic SBRT Planning 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.	Standard SBRT Planning 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.
Overall Study STARTED	10	5
Overall Study COMPLETED	9	5
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Theragnostic SBRT Planning 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.	Standard SBRT Planning 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.
Overall Study Alternative Therapy	1	0

Baseline Characteristics

A Pilot Study to Assess Theragnostically Planned Liver Radiation to Optimize Radiation Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Theragnostic SBRT Planning n=10 Participants 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.	Standard SBRT Planning n=5 Participants 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.	Total n=15 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Age, Continuous	63.8 years STANDARD_DEVIATION 9.65 • n=5 Participants	64.6 years STANDARD_DEVIATION 6.36 • n=7 Participants	64.1 years STANDARD_DEVIATION 8.46 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	4 Participants n=7 Participants	14 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Karnofsky Performance Status KPS 100	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Karnofsky Performance Status KPS 90	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Karnofsky Performance Status KPS 80	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Baseline MELD Score	10.2 units on a scale STANDARD_DEVIATION 4.8 • n=5 Participants	10.8 units on a scale STANDARD_DEVIATION 3.7 • n=7 Participants	10.4 units on a scale STANDARD_DEVIATION 4.4 • n=5 Participants

PRIMARY outcome

Timeframe: Day -1 of Radiation Treatment

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Difference in Functional Reserve of Liver Between Theragnostic SBRT Planning and Standard SBRT Planning	0.22 %/min/m^2 Standard Deviation 0.25	0.02 %/min/m^2 Standard Deviation 0.07

SECONDARY outcome

Timeframe: Day -1 of Radiation Treatment

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes. The two study arms are combined for this analysis because the arm was assigned based on the SBRT planning scheme that was ultimately chosen.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=14 Participants 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.	Standard SBRT Planning 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.
Percentage of Participants for Whom Theragnostically Planned Radiation is Chosen for the Radiation Treatment Plan	64.3 percentage of participants Interval 39.2 to 89.4	—

SECONDARY outcome

Timeframe: Up to 15 months

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Duration of Local Control	NA months The median and associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.	NA months Interval 3.7 to The median and one of the associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.

SECONDARY outcome

Timeframe: Up to 15 months

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Progression Free Survival	NA months Interval 1.3 to The median and one of the associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.	NA months Interval 3.9 to The median and one of the associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.

SECONDARY outcome

Timeframe: Up to 3 years

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Overall Survival	23.9 months Interval 5.2 to 23.9	27.5 months Interval 1.4 to 27.5

SECONDARY outcome

Timeframe: Up to 15 months

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Time to Transplant	NA months No patients received transplant, so the median and associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.	NA months No patients received transplant, so the median and associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.

SECONDARY outcome

Timeframe: Up to 15 months

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Time to Distant Liver Failure	NA months Interval 3.8 to The median and one of the associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.	NA months Interval 3.9 to The median and one of the associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.

SECONDARY outcome

Timeframe: Up to 15 months

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Time Until Salvage Treatment	NA months Interval 2.5 to The median and one of the associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.	NA months The median and associated confidence intervals were not estimable. The median was not reached and the Kaplan-Meier estimate makes no inference about survival times beyond the range of times found in the data.

SECONDARY outcome

Timeframe: Every 15 days for approximately 6 months

Population: Patients who received at least one dose of radiation.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Number of Patients With Treatment-Related Adverse Events Grade 3 or Above	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: Patients who received at least one dose of radiation and completed both SBRT planning schemes. Patient numbers differ due to missed visits and/or patients no longer being on study.

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.

Outcome measures

Outcome measures
Measure	Theragnostic SBRT Planning n=9 Participants 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.	Standard SBRT Planning n=5 Participants 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.
Change in MELD Score Change from Baseline 12 Month	1.4 units on a scale Standard Deviation 1.8	-1.8 units on a scale Standard Deviation 2.1
Change in MELD Score Baseline MELD Score	8.8 units on a scale Standard Deviation 1.9	10.8 units on a scale Standard Deviation 3.7
Change in MELD Score Change from Baseline to Mid-Treatment	0.4 units on a scale Standard Deviation 1.7	-0.4 units on a scale Standard Deviation 0.5
Change in MELD Score Change from Baseline to 1 Month	0.2 units on a scale Standard Deviation 1.2	1.8 units on a scale Standard Deviation 8.6
Change in MELD Score Change from Baseline to 3 Month	0.8 units on a scale Standard Deviation 3.9	-2.0 units on a scale Standard Deviation 2.8
Change in MELD Score Change from Baseline to 6 Month	1.0 units on a scale Standard Deviation 1.9	-2.0 units on a scale Standard Deviation 3.7

Adverse Events

Theragnostic SBRT Planning

Serious events: 3 serious events

Other events: 9 other events

Deaths: 4 deaths

Standard SBRT Planning

Serious events: 1 serious events

Other events: 4 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Theragnostic SBRT Planning n=9 participants at risk 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.	Standard SBRT Planning n=5 participants at risk 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.
Gastrointestinal disorders Abdominal pain	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Gastrointestinal disorders Small intestinal obstruction	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Infections and infestations Sepsis	11.1% 1/9 • Number of events 2 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Renal and urinary disorders Acute kidney injury	0.00% 0/9 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years

Other adverse events

Other adverse events
Measure	Theragnostic SBRT Planning n=9 participants at risk 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.	Standard SBRT Planning n=5 participants at risk 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.
Blood and lymphatic system disorders Anemia	55.6% 5/9 • Number of events 12 • Up to 2 years	40.0% 2/5 • Number of events 5 • Up to 2 years
Gastrointestinal disorders Abdominal pain	22.2% 2/9 • Number of events 3 • Up to 2 years	0.00% 0/5 • Up to 2 years
Gastrointestinal disorders Ascites	22.2% 2/9 • Number of events 2 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Constipation	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Gastrointestinal disorders Gastroesophageal reflux disease	11.1% 1/9 • Number of events 1 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Gastrointestinal disorders Nausea	0.00% 0/9 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
General disorders Chills	11.1% 1/9 • Number of events 3 • Up to 2 years	0.00% 0/5 • Up to 2 years
General disorders Fatigue	55.6% 5/9 • Number of events 5 • Up to 2 years	40.0% 2/5 • Number of events 2 • Up to 2 years
Investigations Alanine aminotransferase increased	11.1% 1/9 • Number of events 2 • Up to 2 years	0.00% 0/5 • Up to 2 years
Investigations Alkaline phosphatase increased	33.3% 3/9 • Number of events 3 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Investigations Aspartate aminotransferase increased	33.3% 3/9 • Number of events 5 • Up to 2 years	40.0% 2/5 • Number of events 2 • Up to 2 years
Investigations Blood bilirubin increased	22.2% 2/9 • Number of events 4 • Up to 2 years	40.0% 2/5 • Number of events 2 • Up to 2 years
Investigations INR increased	22.2% 2/9 • Number of events 3 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Investigations Lymphocyte count decreased	33.3% 3/9 • Number of events 7 • Up to 2 years	80.0% 4/5 • Number of events 7 • Up to 2 years
Investigations Platelet count decreased	22.2% 2/9 • Number of events 4 • Up to 2 years	60.0% 3/5 • Number of events 5 • Up to 2 years
Investigations White blood cell decreased	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Metabolism and nutrition disorders Anorexia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/9 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Hypernatremia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Metabolism and nutrition disorders Hypoalbuminemia	55.6% 5/9 • Number of events 7 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Metabolism and nutrition disorders Hypokalemia	22.2% 2/9 • Number of events 2 • Up to 2 years	0.00% 0/5 • Up to 2 years
Metabolism and nutrition disorders Hyponatremia	33.3% 3/9 • Number of events 3 • Up to 2 years	20.0% 1/5 • Number of events 3 • Up to 2 years
Nervous system disorders Peripheral sensory neuropathy	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Psychiatric disorders Insomnia	11.1% 1/9 • Number of events 1 • Up to 2 years	0.00% 0/5 • Up to 2 years
Respiratory, thoracic and mediastinal disorders Sleep apnea	0.00% 0/9 • Up to 2 years	20.0% 1/5 • Number of events 1 • Up to 2 years
Vascular disorders Hypertension	0.00% 0/9 • Up to 2 years	20.0% 1/5 • Number of events 4 • Up to 2 years

Additional Information

Dr. Ryan Rhome

IndianaU

Phone: (317) 944-1367

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place