Trial Outcomes & Findings for Efficacy Evaluation of TheraSphere to Treat Inoperable Liver Cancer With Blockage of the Portal Vein (NCT NCT01887717)
NCT ID: NCT01887717
Last Updated: 2021-04-21
Results Overview
OS was calculated as the interval between the randomization date and the date of death for any cause, with censoring at the date of last contact for participants alive.
Recruitment status
TERMINATED
Study phase
PHASE3
Target enrollment
36 participants
Primary outcome timeframe
Randomization up to participant's death (maximum time = up to Month 30)
Results posted on
2021-04-21
Participant Flow
Participant enrollment started on February 27, 2014 and was terminated prematurely on March 31, 2016 due to slow recruitment, after randomization of 36 participants. Participants were enrolled at 13 centers in 6 countries (United States, Belgium, Spain, France, England, and Italy).
Participants were randomized 1:1 to the TheraSphere group or control group. To balance the treatment groups, participants were stratified at randomization on the basis of serum level of alpha-fetoprotein (AFP) (\<400 nanograms/milliliter \[ng/mL\] versus \>400 ng/mL) and study center.
Participant milestones
| Measure |
TheraSphere
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Overall Study
STARTED
|
17
|
19
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
15
|
16
|
|
Overall Study
COMPLETED
|
11
|
8
|
|
Overall Study
NOT COMPLETED
|
6
|
11
|
Reasons for withdrawal
| Measure |
TheraSphere
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
7
|
|
Overall Study
Physician Decision
|
0
|
2
|
|
Overall Study
Administrative reasons
|
5
|
2
|
Baseline Characteristics
Efficacy Evaluation of TheraSphere to Treat Inoperable Liver Cancer With Blockage of the Portal Vein
Baseline characteristics by cohort
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
Total
n=31 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
67.2 years
STANDARD_DEVIATION 8.39 • n=5 Participants
|
64.4 years
STANDARD_DEVIATION 8.73 • n=7 Participants
|
65.8 years
STANDARD_DEVIATION 8.54 • n=5 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
3 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
9 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
12 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
27 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
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
AFP
|
3260.6 ng/mL
STANDARD_DEVIATION 10846.39 • n=5 Participants
|
5365.6 ng/mL
STANDARD_DEVIATION 15538.93 • n=7 Participants
|
4347.1 ng/mL
STANDARD_DEVIATION 13295.61 • n=5 Participants
|
PRIMARY outcome
Timeframe: Randomization up to participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib.
OS was calculated as the interval between the randomization date and the date of death for any cause, with censoring at the date of last contact for participants alive.
Outcome measures
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Overall Survival (OS) From Time of Randomization
|
14.5 months
Interval 2.3 to 22.0
|
18.2 months
Interval 2.9 to 18.2
|
SECONDARY outcome
Timeframe: Randomization up to participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib.
TTP was defined as the time from randomization until date of first radiological progression (including new liver lesions and extra-hepatic lesions) separately according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 criteria, modified RECIST (mRECIST) criteria, and European Association for the Study of the Liver (EASL) criteria (assessed bi-dimensionally on enhancing tissue) as assessed by Investigator determination. Progression was defined as an increase \>25% in the size of ≥1 measurable lesions (EASL) and ≥20% increase in the sum of the diameter of viable of target lesion (mRECIST). RECIST v1.1 categorized new lesions as Progressive Disease. TTP (Months)=(Date of event/censor - Date of Randomization + 1)/ 30.4375.
Outcome measures
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Time to Progression (TTP)
mRECIST Criteria
|
17.0 months
Interval 1.6 to 18.7
|
4.1 months
Interval 1.6 to 29.2
|
|
Time to Progression (TTP)
RECIST 1.1 Criteria
|
6.2 months
Interval 1.6 to 18.7
|
3.7 months
Interval 1.6 to 29.2
|
|
Time to Progression (TTP)
EASL Criteria
|
8.1 months
Interval 1.6 to 18.7
|
3.5 months
Interval 1.6 to 5.5
|
SECONDARY outcome
Timeframe: Baseline (Randomization) up to participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib.
Time of randomization to time of any change in classification of PVT type by ≥1 sub-type based on Investigator assessment. At screening and every 8 weeks after, PVT categorized based on dynamic imaging studies as: Type I: segmental, in ≥1 of 8 branches of the portal vein; Type II: branched, left or right branches of the portal vein; Type III: modified on the basis of extension of the tumor thrombus; Type IIIa: eligible for study, thrombus involving the main trunk, allowing blood flow to contralateral lobe (no thrombosis); Type IIIb: NOT eligible for study, thrombus in the main portal trunk occluding blood flow to contralateral lobe; and Type IV: main PVT, NOT eligible for study, extended (mesenteric or splenic veins and/or sovra-hepatic veins). Time to Worsening of PVT (Months)=(Date of event/censor-Date of Randomization+1)/30.4375. Median time to event defined as time it is expected for half of the participants to experience the event. Data analyzed using the Kaplan-Meier method.
Outcome measures
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Time to Worsening Portal Vein Thrombosis (PVT)
|
8.2 months
Interval 5.7 to
NA=Not available. Too few participants experienced the event to estimate the upper limit using the Kaplan-Meier method.
|
NA months
Interval 1.9 to
Too few participants experienced the event to estimate the median and upper limit using the Kaplan-Meier method.
|
SECONDARY outcome
Timeframe: Randomization up to participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib.
TTSP calculated as interval between randomization and symptomatic progression. Symptomatic progression defined as clinical progress to Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 with or without tumor progression on imaging. Deterioration in PS was confirmed at the evaluation 8 weeks later. First date at which ECOG performance status was ≥2 was used as end date in TTSP analysis (assuming next subsequent visit confirmed deterioration). TTSP (Months)=(Date of ECOG \>2-Date of Randomization+1)/30.4375. ECOG PS Scale: 0=Asymptomatic and fully active; 1=Symptomatic, fully ambulatory, restricted in physically strenuous activity; 2=Symptomatic, ambulatory, capable of self-care, more than 50% of waking hours are spent out of bed; 4=Completely disabled, no self-care, bedridden. Median time to event defined as time it is expected for half of the participants to experience the event. Data analyzed using the Kaplan-Meier method.
Outcome measures
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Time to Symptomatic Progression (TTSP)
|
NA months
Interval 20.3 to
Too few participants experienced the event to estimate the median and upper limit using the Kaplan-Meier method.
|
NA months
Too few participants experienced the event to estimate the median, lower limit, and upper limit using the Kaplan-Meier method.
|
SECONDARY outcome
Timeframe: Baseline up to participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib and with available Tumor Response data.
Tumor Response was based on the radiological tumor assessment and was categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). Tumor response was assessed using RECIST version (v) 1.1, mRECIST, and EASL criteria. Criteria included: CR=disappearance of all enhanced tumor areas (EASL) and disappearance of any intratumoral arterial enhancement in all target lesions (mRECIST); PR= decrease \>50% of enhanced areas (EASL) and ≥30% decrease in the sum of diameters of viable target lesions (mRECIST); SD=neither CR, PR, PD (EASL/mRECIST); PD=an increase \>25% in the size of ≥1 measurable lesions (EASL) and ≥20% increase in the sum of the diameter of viable of target lesion (mRECIST). RECIST v 1.1 categorized new lesions as Progressive Disease only and the non-target lesions needed to have no progressive disease to be categorized as CR or PR. One month=30.4375 days.
Outcome measures
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Number of Participants With Tumor Response
RECIST CR
|
0 Participants
|
0 Participants
|
|
Number of Participants With Tumor Response
RECIST PR
|
1 Participants
|
0 Participants
|
|
Number of Participants With Tumor Response
mRECIST CR
|
0 Participants
|
0 Participants
|
|
Number of Participants With Tumor Response
mRECIST PR
|
1 Participants
|
0 Participants
|
|
Number of Participants With Tumor Response
EASL CR
|
0 Participants
|
0 Participants
|
|
Number of Participants With Tumor Response
EASL PR
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Baseline (Randomization), participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib and with evaluable TOI data.
The Functional Assessment Cancer of Therapy-Hepatobiliary (FACT-Hep) Questionnaire uses participant reported outcome (PRO) scores. The FACT-Hep Trial Outcome Index (TOI) is the sum of the subscales scores in Personal Well-Being (PWB), Functional Well-Being (FWB), and Hepatobiliary Cancer Subscale (HCS). The higher the score, the better the QoL, with a range 0-128. Baseline data and change from Baseline data is presented.
Outcome measures
| Measure |
TheraSphere
n=13 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=14 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Change From Baseline in Quality of Life (QoL) as Assessed by the FACT-Hep Questionnaire
Baseline TOI
|
94.63 score on a scale
Standard Deviation 16.692
|
103.54 score on a scale
Standard Deviation 14.934
|
|
Change From Baseline in Quality of Life (QoL) as Assessed by the FACT-Hep Questionnaire
Month 30 TOI
|
-5.20 score on a scale
Standard Deviation NA
Standard deviation cannot be calculated with an N of 1.
|
—
|
SECONDARY outcome
Timeframe: Baseline (Randomization) up to participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib.
TTDQoL was calculated as the interval between the randomization date and deterioration in QoL. The FACT-Hep Questionnaire uses PRO scores. A deterioration in QoL is defined as a \>7-point decline in the total score or death, whichever occurred first. The FACT-Hep Total Score is the sum of the subscales scores in PWB, Social/Family Well-Being (SWB), Emotional Well-Being (EWB), FWB, and HCS. The higher the score, the better the QoL, with a range 0-180. TTDQoL (Months)=(Date of change from baseline in FACT-Hep ≥7 or death) - Date of Randomization + 1.
Outcome measures
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Time to Deterioration QoL (TTDQoL)
|
2.5 months
Interval 0.6 to 24.0
|
1.6 months
Interval 0.9 to 9.0
|
SECONDARY outcome
Timeframe: Randomization up to participant's death (maximum time = up to Month 30)Population: Participants who received at least 1 dose of TheraSphere or Sorafenib.
An TEAE is any untoward medical occurrence or undesirable event(s) experienced in a participant that begins or worsens following administration of the study drug or study treatment, whether or not considered related to the treatment by the Investigator. A serious adverse event (SAE) was an adverse event (AE) resulting in any of the following outcomes or deemed significant for any other reason, death, initial or prolonged inpatient hospitalization, life-threatening experience (immediate risk of dying), persistent or significant disability/incapacity, or congenital anomaly. AEs included both SAEs and non-serious AEs. AEs were classified according to National Cancer Institute Common Terminology Criteria for Adverse Events v4.0 (CTCAE) and coded using the Medical Dictionary for Regulatory Activities (MedDRA). A summary of serious and all other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events module.
Outcome measures
| Measure |
TheraSphere
n=15 Participants
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 Participants
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Angiographic Related TEAE
|
3 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
TEAE
|
6 Participants
|
16 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Adverse Device Event (ADE)
|
3 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
TEAE CTCAE ≥ Grade 3
|
1 Participants
|
9 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Treatment Emergent SAE
|
0 Participants
|
7 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
Related Serious Adverse Device Effect (SADE)
|
0 Participants
|
0 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
TEAE with an Outcome of Death
|
0 Participants
|
4 Participants
|
|
Number of Participants With Treatment Emergent Adverse Events (TEAE)
TEAE with Action Taken of Sorafenib Discontinued
|
0 Participants
|
2 Participants
|
Adverse Events
TheraSphere
Serious events: 0 serious events
Other events: 6 other events
Deaths: 15 deaths
Sorafenib
Serious events: 12 serious events
Other events: 16 other events
Deaths: 16 deaths
Serious adverse events
| Measure |
TheraSphere
n=15 participants at risk
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 participants at risk
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
12.5%
2/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
General Physical Health Deterioration
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
Influenza like illness
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Gastrointestinal vascular malformation
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Haematemesis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
Other adverse events
| Measure |
TheraSphere
n=15 participants at risk
Participants received TheraSphere at a dose consistent with the approved package insert to the treated lobe of the liver. TheraSphere was administered through the hepatic artery. The targeted dose was 120 Gy + 10%. Dose reduction to a minimum dose of 80 Gy + 10% was permitted to manage radiation exposure to the lungs. Re-treatment of the same participant/lobe with further cycles of TheraSphere was permitted if a treatable progression was detected during follow-up evaluations. Any re-treatment took place at least 28 days after the previous TheraSphere treatment administered to that lobe. Participants could receive a subsequent TheraSphere administration in the absence of radiological progression criteria at the Investigator's discretion. A maximum of 3 TheraSphere administrations was permitted.
|
Sorafenib
n=16 participants at risk
Participants received sorafenib, oral tablets, 400 milligrams (mg) twice daily in accordance with the package insert. Treatment was to continue until the participant was no longer clinically benefiting from therapy or until unacceptable toxicity occurred. Medically appropriate dose adjustments and drug holidays due to adverse events (AEs) and toxicity were allowed.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
12.5%
2/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Aphthous Stomatitis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Ascites
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
18.8%
3/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
43.8%
7/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Flatulence
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Nausea
|
20.0%
3/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Steatorrhoea
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
12.5%
2/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
Asthenia
|
13.3%
2/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
31.2%
5/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
Disease progression
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
Fatigue
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
12.5%
2/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
General physical health deterioration
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
Oedema peripheral
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
25.0%
4/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
Pain
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
General disorders
Pyrexia
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Hepatobiliary disorders
Cytolytic hepatitis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Hepatobiliary disorders
Hepatic pain
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Infections and infestations
Bronchitis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Infections and infestations
Localised infection
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Infections and infestations
Sepsis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
12.5%
2/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Investigations
Eosinophil count decreased
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Investigations
Weight decreased
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Investigations
Weight increased
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.3%
2/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
12.5%
2/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tongue neoplasm benign
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Nervous system disorders
Hepatic encephalopathy
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
18.8%
3/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Nervous system disorders
Memory impairment
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Nervous system disorders
Mental impairment
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Nervous system disorders
Presyncope
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Psychiatric disorders
Anxiety
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Psychiatric disorders
Depression
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Reproductive system and breast disorders
Gynaecomastia
|
0.00%
0/12 • Randomization up to participant's death (maximum time = up to Month 30)
|
7.7%
1/13 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Reproductive system and breast disorders
Scrotal erythema
|
0.00%
0/12 • Randomization up to participant's death (maximum time = up to Month 30)
|
7.7%
1/13 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
12.5%
2/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Skin and subcutaneous tissue disorders
Dermatitis bullous
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Skin and subcutaneous tissue disorders
Pain of skin
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
25.0%
4/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
18.8%
3/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Vascular disorders
Hyperaemia
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
6.2%
1/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Vascular disorders
Hypertension
|
0.00%
0/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
18.8%
3/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Vascular disorders
Peripheral coldness
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
|
Vascular disorders
Venous thrombosis
|
6.7%
1/15 • Randomization up to participant's death (maximum time = up to Month 30)
|
0.00%
0/16 • Randomization up to participant's death (maximum time = up to Month 30)
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee BTG can require Investigator to postpone publications/presentations for up to 12 months so data from all sites can be published. BTG will limit review of Investigator's draft to confirm Confidential Information is not being disclosed. If BTG notes publishing Study results may affect obtaining a patent, Investigator will not publish for up to 60 days until patent application is filed. Investigator will acknowledge BTG in any publication/presentation.
- Publication restrictions are in place
Restriction type: OTHER