Trial Outcomes & Findings for A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma (NCT NCT02460835)
NCT ID: NCT02460835
Last Updated: 2023-11-15
Results Overview
The primary aim of the trial is feasibility which is defined as the ability to successfully deliver the full treatment including all adaptations and in particular the perfusion-based planning and replanning.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
77 participants
Primary outcome timeframe
At end of treatment; up to ~3 months
Results posted on
2023-11-15
Participant Flow
Participant milestones
| Measure |
Adaptive Radiation Therapy
Adaptive Radiation Therapy
|
|---|---|
|
Overall Study
STARTED
|
77
|
|
Overall Study
COMPLETED
|
56
|
|
Overall Study
NOT COMPLETED
|
21
|
Reasons for withdrawal
| Measure |
Adaptive Radiation Therapy
Adaptive Radiation Therapy
|
|---|---|
|
Overall Study
Disease progression prior to treatment
|
3
|
|
Overall Study
Unable to complete planning scans
|
2
|
|
Overall Study
Decrease in performance status
|
1
|
|
Overall Study
Withdrawal by Subject
|
3
|
|
Overall Study
Underwent fractionated RT
|
10
|
|
Overall Study
Unable to complete follow-up lab draws
|
2
|
Baseline Characteristics
A Pilot Study of Individualized Adaptive Radiation Therapy for Hepatocellular Carcinoma
Baseline characteristics by cohort
| Measure |
Adaptive Radiation Therapy
n=77 Participants
Adaptive Radiation Therapy
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
42 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
35 Participants
n=5 Participants
|
|
Age, Continuous
|
63 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
55 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
71 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
68 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
77 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At end of treatment; up to ~3 monthsPopulation: 77 subjects enrolled, 70 subjects treated
The primary aim of the trial is feasibility which is defined as the ability to successfully deliver the full treatment including all adaptations and in particular the perfusion-based planning and replanning.
Outcome measures
| Measure |
Adaptive Radiation Therapy
n=77 Participants
Adaptive Radiation Therapy
|
|---|---|
|
The Proportion of Patients for Whom the Intended Treatment Was Feasible
|
70 Participants
|
PRIMARY outcome
Timeframe: Baseline to approximately 6 months after initiation of SBRTPopulation: 77 subjects enrolled, 70 subjects treated, 56 eligible for analysis (14 were excluded: 10- fractionated RT, 2- unable to complete follow up, 2- withdrew)
Rate of liver decompensation reported as the percentage of patients with a change in Child Pugh score of greater than or equal to 2 within 6 months of SBRT.
Outcome measures
| Measure |
Adaptive Radiation Therapy
n=56 Participants
Adaptive Radiation Therapy
|
|---|---|
|
Percentage of Patients With Change in Child Pugh Score >= 2
|
12 Participants
|
PRIMARY outcome
Timeframe: 24 monthsPopulation: 77 subjects enrolled, 70 subjects treated, 9 eligible for analysis
The primary efficacy endpoint is local control, measured as the duration of time from start of treatment to time of progression of the treated (target) lesion(s). Patients with no evidence of local progression at the time of data analysis will be censored at the last date on which they were evaluated for local progression. Local progression will be summarized with Kaplan-Meier curves and reported with 95% confidence intervals.
Outcome measures
| Measure |
Adaptive Radiation Therapy
n=9 Participants
Adaptive Radiation Therapy
|
|---|---|
|
Median Time to Local Progression
|
17.4 Months
Interval 4.93 to 25.27
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: 77 subjects enrolled, 70 subjects treated, 31 eligible for analysis
Defined as the duration of time from start of treatment to time of progression.
Outcome measures
| Measure |
Adaptive Radiation Therapy
n=31 Participants
Adaptive Radiation Therapy
|
|---|---|
|
Median Time to Progression
|
5.23 months
Interval 4.57 to 9.03
|
SECONDARY outcome
Timeframe: Approximately 6 monthsPopulation: 77 subjects enrolled, 70 subjects treated, 56 eligible for analysis (14 were excluded: 10- fractionated RT, 2- unable to complete follow up, 2- withdrew)
Liver decompensation assessed by change in ALBI score \> 0.5 from baseline.
Outcome measures
| Measure |
Adaptive Radiation Therapy
n=56 Participants
Adaptive Radiation Therapy
|
|---|---|
|
Change in ALBI Scores
|
15 Participants
|
SECONDARY outcome
Timeframe: Approximately 6 monthsPopulation: 77 subjects enrolled, 70 subjects treated, 56 eligible for analysis (14 were excluded: 10- fractionated RT, 2- unable to complete follow up, 2- withdrew)
Grade 3 GI bleeding assessed via the NCI CTCAE version 4.0.
Outcome measures
| Measure |
Adaptive Radiation Therapy
n=56 Participants
Adaptive Radiation Therapy
|
|---|---|
|
Incidence of Grade 3 Gastrointestinal (GI) Bleeding Toxicities
|
0 Participants
|
SECONDARY outcome
Timeframe: 24 monthsPopulation: 77 subjects enrolled, 70 subjects treated, 54 eligible for analysis
Overall survival (OS) is defined as the duration of time from start of treatment to death.
Outcome measures
| Measure |
Adaptive Radiation Therapy
n=54 Participants
Adaptive Radiation Therapy
|
|---|---|
|
Overall Survival
|
16.8 Months
Interval 10.67 to 28.47
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 24 monthsRILD is a rare but serious side effect that will be summarized if it occurs.
Outcome measures
Outcome data not reported
Adverse Events
Adaptive Radiation Therapy
Serious events: 6 serious events
Other events: 67 other events
Deaths: 19 deaths
Serious adverse events
| Measure |
Adaptive Radiation Therapy
n=77 participants at risk
Adaptive Radiation Therapy
|
|---|---|
|
Gastrointestinal disorders
Abdominal Pain
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Renal and urinary disorders
Acute Kidney Injury
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Infections and infestations
Catheter Related Infection
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Nervous system disorders
Encephalopathy
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Nausea
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Infections and infestations
Urinary tract infection
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
Other adverse events
| Measure |
Adaptive Radiation Therapy
n=77 participants at risk
Adaptive Radiation Therapy
|
|---|---|
|
Blood and lymphatic system disorders
Anemia
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Cardiac disorders
Heart failure
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Cardiac disorders
Palpitations
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Abdominal distension
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Abdominal Pain
|
9.1%
7/77 • Number of events 7 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Ascites
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Constipation
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Diarrhea
|
3.9%
3/77 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Gastritis
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Nausea
|
16.9%
13/77 • Number of events 13 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Gastrointestinal disorders
Vomiting
|
7.8%
6/77 • Number of events 6 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
General disorders
Chills
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
General disorders
Edema Limbs
|
2.6%
2/77 • Number of events 3 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
General disorders
Fatigue
|
40.3%
31/77 • Number of events 34 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
General disorders
Multi-organ Failure
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Hepatobiliary disorders
Hepatic Pain
|
6.5%
5/77 • Number of events 5 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Investigations
Alkaline phosphatase increased
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Investigations
Blood Bilirubin increased
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Nervous system disorders
dizziness
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Nervous system disorders
Encephalopathy
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Psychiatric disorders
Confusion
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Psychiatric disorders
Depression
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Renal and urinary disorders
Cystitis noninfective
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Renal and urinary disorders
Hematuria
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
2.6%
2/77 • Number of events 2 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural Effusion
|
1.3%
1/77 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 2 years after last dose of study treatment. Data was collected over 6 years.
|
Additional Information
Dr. Theodore Lawrence
University of Michigan Rogel Cancer Center
Phone: 734-647-9955
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place