Trial Outcomes & Findings for Stereotactic Body Radiation Therapy (SBRT) Versus Trans-Arterial Chemoembolization (TACE) as Bridge to Liver Transplant (NCT NCT02182687)

Last Updated: 2024-03-05

Results Overview

Time from SBRT and TACE intervention to progression was tracked for subject receiving protocol intervention. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

3, 6 and 12 Months

Results posted on

2024-03-05

Participant Flow

Participant milestones

Participant milestones
Measure	Arm A Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Overall Study STARTED	24	30
Overall Study COMPLETED	19	29
Overall Study NOT COMPLETED	5	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Arm A Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Overall Study Withdrawal by Subject	4	0
Overall Study Adverse Event	1	0
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Arm A n=19 Participants Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 Participants Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.	Total n=48 Participants Total of all reporting groups
Age, Continuous	63.2 years STANDARD_DEVIATION 4.6 • n=19 Participants	61.7 years STANDARD_DEVIATION 6.2 • n=29 Participants	62.5 years STANDARD_DEVIATION 5.4 • n=48 Participants
Sex: Female, Male Female	3 Participants n=19 Participants	6 Participants n=29 Participants	9 Participants n=48 Participants
Sex: Female, Male Male	16 Participants n=19 Participants	23 Participants n=29 Participants	39 Participants n=48 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	19 participants n=19 Participants	29 participants n=29 Participants	48 participants n=48 Participants

PRIMARY outcome

Timeframe: 3, 6 and 12 Months

Outcome measures

Outcome measures
Measure	Arm A n=19 Participants Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 Participants Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Freedom From Progression Over Time 3 Month	0 percentage of patients with progression Interval 0.0 to 0.0	3.4 percentage of patients with progression Interval 0.5 to 22.1
Freedom From Progression Over Time 6 Month	0 percentage of patients with progression Interval 0.0 to 0.0	26.5 percentage of patients with progression Interval 13.5 to 47.9
Freedom From Progression Over Time 12 Month	11.1 percentage of patients with progression Interval 1.6 to 56.7	38.0 percentage of patients with progression Interval 21.1 to 61.8

SECONDARY outcome

Timeframe: At each treatment, 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment

Population: Subjects in both arms were observed for adverse events at protocol specific time points.

Grade 3 or greater toxicity with treatment-related adverse events was tracked at protocol specific time points. Grading of events was according to CTCAE.

Outcome measures

Outcome measures
Measure	Arm A n=19 Participants Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 Participants Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Toxicity To Compare Participants With Treatment-related Adverse Events as Assessed by CTCAE	1 Participants	3 Participants

SECONDARY outcome

Timeframe: 2 weeks post treatment, 2 months post treatment, 5 months post treatment, every 3 months until 24 months post treatment

Each patient on each arm was followed to see how if further treatment interventions were needed prior to liver transplant. This outcome summarizes the number of participants who needed further treatment.

Outcome measures

Outcome measures
Measure	Arm A n=19 Participants Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 Participants Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Number of Participants Who Require Further Interventions Prior to Liver Transplant	1 participants	6 participants

SECONDARY outcome

Timeframe: At time of liver transplant

Population: Patients undergoing liver transplant were reviewed for complete pathologic response.

Pathologic complete response was recorded for patients in both arms after completion of liver transplant. Explanted liver was reviewed by the pathologist to determine if residual tumor was identified.

Outcome measures

Outcome measures
Measure	Arm A n=19 Participants Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 Participants Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Pathologic Response of Treated Lesion(s) Count of participants undergoing Liver Transplant	15 Participants	20 Participants
Pathologic Response of Treated Lesion(s) Patients having a complete pathologic response to therapy	4 Participants	7 Participants
Pathologic Response of Treated Lesion(s) Patients having additional HCC outside the treated area	6 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline, 3 months post-treatment, 6 months post-treatment, every 3 months thereafter until 2 years post treatment

Number of patients with a radiographical response to treatment.The status of each treated tumor/target lesion was assessed by MRI or CT scan and classified as progression if there was tumor growth (excluding growth due to biloma or abscess formation), residual or new enhancement of the ablated tumor (excluding benign peri-ablational enhancement), or contiguous viable tumor as determined by mRECIST Criteria.

Outcome measures

Outcome measures
Measure	Arm A n=19 Participants Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 Participants Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Radiologic Response of Treat Lesion(s)	18 Participants	23 Participants

SECONDARY outcome

Timeframe: Baseline, 2 weeks post-treatment, 6 months post-treatment

Quality of life was assessed with Short Form 36 Health Survey (SF-36v2®) and Pain Impact Questionnaire (PIQ-6TM) Health Survey. Data was stored and scored with Pro CoRE 2.0 Smart Measurement® System. Scores were analyzed at three time points, baseline-before the first treatment, acute response-2 weeks post the first treatment, and long term response - 6 months after the first treatment. The PIQ-6 Pain Impact Questionnaire measures how a subject's pain affects every day activities. The SF-36v2 Health Survey measures functional health and well-being from the subject's point of view. The survey's scores range from 0-100, with 0 having the most disability and a score of 100 being equivalent to no disability.

Outcome measures

Outcome measures
Measure	Arm A n=19 Participants Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 Participants Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey SF36-Mental Component Score (baseline)	50.2 score on a scale Standard Deviation 9.4	49.9 score on a scale Standard Deviation 7.6
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey SF36-Mental Component Score (2-week)	49.7 score on a scale Standard Deviation 9.8	48.7 score on a scale Standard Deviation 8.8
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey SF36-Mental Component Score (6 Months)	53.8 score on a scale Standard Deviation 7.1	50.9 score on a scale Standard Deviation 8.3
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey SF36-Physical Component Score (baseline)	48.1 score on a scale Standard Deviation 9.7	48.3 score on a scale Standard Deviation 9.0
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey SF36-Physical Component Score (2 weeks)	44.2 score on a scale Standard Deviation 9.8	44.7 score on a scale Standard Deviation 9.5
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey SF36-Physical Component Score (6 Months)	49.6 score on a scale Standard Deviation 5.8	45.1 score on a scale Standard Deviation 10.3
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey Pain Summary score -hand weighted (baseline)	49.9 score on a scale Standard Deviation 9.3	49.5 score on a scale Standard Deviation 10.0
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey Pain Summary Score - hand weighted (2 weeks)	51.4 score on a scale Standard Deviation 8.0	54.2 score on a scale Standard Deviation 9.8
Quality of Life - Questionnaires Include PIQ-6 and SF-36v2 Health Survey Pain Summary Score - hand weighted (6 Months)	47.2 score on a scale Standard Deviation 8.3	50.1 score on a scale Standard Deviation 8.7

Adverse Events

Arm A

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Arm B

Serious events: 2 serious events

Other events: 5 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Arm A n=19 participants at risk Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 participants at risk Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Gastrointestinal disorders Gastritis and GI Bleed	0.00% 0/19 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	3.4% 1/29 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Hepatobiliary disorders biliary infection	0.00% 0/19 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	3.4% 1/29 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.

Other adverse events

Other adverse events
Measure	Arm A n=19 participants at risk Stereotactic Body Radiation Therapy (SBRT) Stereotactic Body Radiation Therapy (SBRT): SBRT will be delivered in five total fractions, with at a minimum of one day between any two treatments. The entire treatment must be delivered within 15 total days.	Arm B n=29 participants at risk Trans-Arterial Chemoembolization (TACE) Drug: Doxorubin Trans-Arterial Chemoembolization (TACE): First day will be administered and a second TACE will be administered after 4 weeks and subsequently if imaging is showing disease progression. Following each TACE procedure all patients will remain in hospital for observation. Doxorubin: This procedure will be completed with 2 vials of drug eluting beads each loaded with 50 mg of Doxorubin.
Hepatobiliary disorders RILD with refractory ascities	5.3% 1/19 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	0.00% 0/29 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
General disorders fatigue	31.6% 6/19 • Number of events 6 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	0.00% 0/29 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Blood and lymphatic system disorders thrombocytopenia	5.3% 1/19 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	3.4% 1/29 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Hepatobiliary disorders hepatic pain	5.3% 1/19 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	0.00% 0/29 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Gastrointestinal disorders bacterial peritonitis	5.3% 1/19 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	0.00% 0/29 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Blood and lymphatic system disorders WBC decreased	5.3% 1/19 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	6.9% 2/29 • Number of events 2 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Vascular disorders hypertension	5.3% 1/19 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	13.8% 4/29 • Number of events 4 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Blood and lymphatic system disorders anemia	5.3% 1/19 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	0.00% 0/29 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Blood and lymphatic system disorders lymphopenia	0.00% 0/19 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	6.9% 2/29 • Number of events 2 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Hepatobiliary disorders portal vein thrombosis	0.00% 0/19 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	6.9% 2/29 • Number of events 2 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Hepatobiliary disorders hepatic infarct	0.00% 0/19 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	3.4% 1/29 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.
Gastrointestinal disorders esophageal varices hemorrhage	0.00% 0/19 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.	3.4% 1/29 • Number of events 1 • Baseline, During Treatment, post treatment follow-up visit, 3 Month, 6 Month, then every 3 months until 24 month time point.

Additional Information

Julia Roache

Lahey Hospital & Medical Center

Phone: 781-744-3055

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place