Hepatocellular Carcinoma
Conditions
Brief summary
This is a pilot single arm study with the primary endpoints of feasibility and preliminary estimates of safety and efficacy. This protocol builds on over 25 years of experience with high dose liver RT (Radiation Therapy), and in particular adaptive RT aimed at adjusting the global radiation dose based on a patient's measured sensitivity to treatment. This current protocol uses functional imaging and specialized radiation planning techniques to spare highly functional portions of the liver to preserve function. The investigators feel this will further improve the safety and efficacy of RT for all patients by customizing treatments to each. If this approach is promising, the investigators will proceed to a phase II randomized study of standard versus spatially and dosimetrically adapted RT.
Interventions
RADIATIONAdaptive Radiation Therapy
Sponsors
National Institutes of Health (NIH)
University of Michigan Rogel Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have hepatocellular carcinoma. * Patients must not have extrahepatic cancer. * Patients must not be eligible for a curative liver resection or have refused resection * Patients must have recovered from the acute effects of prior liver-directed therapy and 4 weeks must have passed since the last procedure and protocol therapy. * Patients must have a Zubrod performance status of less than or equal to 2 (Zubrod performance status is a measure that attempts to quantify a cancer patients' general well-being. Scores run from 0 to 5 where 0 denotes normal activity and 5 denotes death). * Patients must be 18 years of age or older. * Patients must have adequate organ function. * Patients must understand and be willing to sign an IRB (Institutional Review Board) approved informed consent form.
Exclusion criteria
* Patients with known allergies to intravenous iodinated contrast agents. * Patients with a contraindication to contrast-enhanced MRI are excluded.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Median Time to Local Progression | 24 months | 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. |
| The Proportion of Patients for Whom the Intended Treatment Was Feasible | At end of treatment; up to ~3 months | 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. |
| Percentage of Patients With Change in Child Pugh Score >= 2 | Baseline to approximately 6 months after initiation of SBRT | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade 3 Gastrointestinal (GI) Bleeding Toxicities | Approximately 6 months | Grade 3 GI bleeding assessed via the NCI CTCAE version 4.0. |
| Overall Survival | 24 months | Overall survival (OS) is defined as the duration of time from start of treatment to death. |
| Median Time to Progression | 24 months | Defined as the duration of time from start of treatment to time of progression. |
| Change in ALBI Scores | Approximately 6 months | Liver decompensation assessed by change in ALBI score \> 0.5 from baseline. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Radiation Induced Liver Disease (RILD) | 24 months | RILD is a rare but serious side effect that will be summarized if it occurs. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Adaptive Radiation Therapy Adaptive Radiation Therapy | 77 |
| Total | 77 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Decrease in performance status | 1 |
| Overall Study | Disease progression prior to treatment | 3 |
| Overall Study | Unable to complete follow-up lab draws | 2 |
| Overall Study | Unable to complete planning scans | 2 |
| Overall Study | Underwent fractionated RT | 10 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | Adaptive Radiation Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 35 Participants |
| Age, Categorical Between 18 and 65 years | 42 Participants |
| Age, Continuous | 63 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 68 Participants |
| Region of Enrollment United States | 77 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 55 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 77 |
| other Total, other adverse events | 67 / 77 |
| serious Total, serious adverse events | 6 / 77 |
Outcome results
Primary
Median Time to Local Progression
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.
Time frame: 24 months
Population: 77 subjects enrolled, 70 subjects treated, 9 eligible for analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adaptive Radiation Therapy | Median Time to Local Progression | 17.4 Months |
Primary
Percentage of Patients With Change in Child Pugh Score >= 2
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.
Time frame: Baseline to approximately 6 months after initiation of SBRT
Population: 77 subjects enrolled, 70 subjects treated, 56 eligible for analysis (14 were excluded: 10- fractionated RT, 2- unable to complete follow up, 2- withdrew)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adaptive Radiation Therapy | Percentage of Patients With Change in Child Pugh Score >= 2 | 12 Participants |
Primary
The Proportion of Patients for Whom the Intended Treatment Was Feasible
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.
Time frame: At end of treatment; up to ~3 months
Population: 77 subjects enrolled, 70 subjects treated
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adaptive Radiation Therapy | The Proportion of Patients for Whom the Intended Treatment Was Feasible | 70 Participants |
Secondary
Change in ALBI Scores
Liver decompensation assessed by change in ALBI score \> 0.5 from baseline.
Time frame: Approximately 6 months
Population: 77 subjects enrolled, 70 subjects treated, 56 eligible for analysis (14 were excluded: 10- fractionated RT, 2- unable to complete follow up, 2- withdrew)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adaptive Radiation Therapy | Change in ALBI Scores | 15 Participants |
Secondary
Incidence of Grade 3 Gastrointestinal (GI) Bleeding Toxicities
Grade 3 GI bleeding assessed via the NCI CTCAE version 4.0.
Time frame: Approximately 6 months
Population: 77 subjects enrolled, 70 subjects treated, 56 eligible for analysis (14 were excluded: 10- fractionated RT, 2- unable to complete follow up, 2- withdrew)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Adaptive Radiation Therapy | Incidence of Grade 3 Gastrointestinal (GI) Bleeding Toxicities | 0 Participants |
Secondary
Median Time to Progression
Defined as the duration of time from start of treatment to time of progression.
Time frame: 24 months
Population: 77 subjects enrolled, 70 subjects treated, 31 eligible for analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adaptive Radiation Therapy | Median Time to Progression | 5.23 months |
Secondary
Overall Survival
Overall survival (OS) is defined as the duration of time from start of treatment to death.
Time frame: 24 months
Population: 77 subjects enrolled, 70 subjects treated, 54 eligible for analysis
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Adaptive Radiation Therapy | Overall Survival | 16.8 Months |
Other Pre-specified
Incidence of Radiation Induced Liver Disease (RILD)
RILD is a rare but serious side effect that will be summarized if it occurs.
Time frame: 24 months