Outcome
| Type |
Measure |
Description |
Time frame |
Safety issue |
| Primary |
Overall Survival (OS) |
OS will be calculated as the interval between treatment administration and the date of death for any cause, opposition to data collection, or study termination, whichever occurs first. |
Treatment (Day 1) up to participant's death, opposition to data collection, or study termination (up to Year 6) |
|
| Primary |
QoL Measurements Using FACT-HEP Questionnaire Before and After Treatment |
Quality of Life (QoL) will be assessed by the Functional Assessment of Cancer Therapy (FACT-HEP) questionnaire prior to treatment on Day 1, every 2 to 4 months post treatment (follow up visits), and every standard of care (SOC) visit after Month 12 until the participant's death, opposition to data collection, study withdraw for any cause, or study termination. The FACT-Hep Questionnaire uses participant-reported outcome (PRO) scores. QoL scores of each domain at each time-point and their differences from baseline will be summarised. A deterioration in QoL is defined as a 7-point decline in the total score or death, whichever comes first. The time to deterioration in QoL will be calculated as the interval between first date of TheraSphere® treatment and deterioration in QoL. The higher the score, the better the QoL, with a range 0-180. |
Treatment (Day 1), every 2 to 4 months Post Treatment (maximum treatment time = up to Day 28), and SOC visits after Month 12 until up to participant's death, opposition to data collection, study withdraw for any cause, or study termination (up to Year 6) |
|
| Secondary |
Number of Grade 3 or Higher Adverse Events (AEs) Related to Study treatment or Procedure |
An AE is any untoward medical occurrence or undesirable event experienced in a participant that begins or worsens following TheraSphere® administration. AEs will be classified using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 5.0. |
Treatment (Day 1) up to 90 Days Post Treatment or the first post treatment follow-up visit after TheraSphere administration, if after 90 days (maximum treatment time = up to Day 28) |
|
| Secondary |
Number of Participants Re-Hospitalised Following Treatment |
The number of participants re-hospitalised for any event related to TheraSphere® treatment during the study will be reported. |
Treatment (Day 1) up to Month 1 Post Treatment (maximum treatment time = up to Day 28) |
|
| Secondary |
Duration of Re-Hospitalisations Following Treatment |
The duration of re-hospitalisations for any event related to TheraSphere® treatment during the study will be reported. |
Treatment (Day 1) up to Month 1 Post Treatment (maximum treatment time = up to Day 28) |
|
| Secondary |
Number of Participants Achieving Treatment Expectation |
At Baseline and follow-up post treatment, participants' treatment expectation will be measured by a qualitative assessment according to Investigator's opinion, whether the goal is met or not. Before treatment the treatment goal will be documented. The number of participants achieving the treatment goal will be reported. |
Baseline up to Month 12 Post Treatment |
|
| Secondary |
Number of Participants with Tumour Response |
Tumour Response will be based on the radiological tumour assessment and will be categorized as Complete Response (CR), Partial Response (PR), Stable Disease (SD) or Progressive Disease (PD). Tumour response will be assessed using Modified Response Evaluation Criteria in Solid Tumours (mRECIST) criteria or RECIST criteria |
Treatment (Day 1) up to Month 12 Post Treatment (maximum treatment time = up to Day 28) |
|
| Secondary |
Number of Participants with an Alpha-Fetoprotein (AFP), CA 19-9, CEA tumour Response |
A Tumour response defined as a =50% decrease in: AFP levels for participants with a Baseline AFP level =200 nanograms/milliliter (ng/mL), CA 19-9 levels for participants with a baseline CA 19-9 level = 2 x Upper Limit of Normal (ULN), CEA levels for participants with a baseline CEA level = 2 x ULN. |
Treatment (Day 1) and Month 12 Post Treatment (maximum treatment time = up to Day 28) |
|
| Secondary |
Number of Participants Receiving a Post TheraSphere Anti-Cancer Treatment |
The number of participants for which additional TheraSphere treatment or surgical procedure is required will be reported. |
Treatment (Day 1) up to participant's death, opposition to data collection, study withdraw for any cause, or study termination (up to Year 6) |
|
| Secondary |
Number of Participants Reporting Best Supportive Care Treatment |
The number of participants for which additional anti-cancer treatment including additional TheraSphere treatment or surgical procedure will be reported. |
Treatment (Day 1) up to participant's death, opposition to data collection, study withdraw for any cause, or study termination (up to Year 6) |
|
| Secondary |
Number of Participants per Type of Vascular Access Used to Administer TheraSphere |
The number of participants recorded for each type of vascular access (that is, Femoral/Radial-Humeral) will be reported. |
Treatment (Day1) upto Month 12 |
|
| Secondary |
Number of Participants with similar Tumour(s) Location at Baseline and the location of lesions targeted by 99mTc-MAA SPECT Imaging |
The Baseline computed tomography (CT)/magnetic resonance imaging (MRI) will be compared against 99mTc-MAA imaging (Single Proton Emission Computed Tomography [SPECT] or SPECT/CT) to evaluate the agreement in the lesion locations identified with 2 imaging methods. The 3 categories to report agreement between Baseline CT/MRI and 99mTc-MAA are: Optimal (images match), Sub optimal (less than 50% matching), and Non optimal (images do not match at all). |
Baseline and Post 99mTc-MAA Imaging (up to Day 28) |
|
| Secondary |
Description of post treatment tumour targeting by determination of the number of patients with similar tumour(s) location at baseline and location of lesions targeted by Y-90 Positron Emission Tomography (PET)/CT or Y-90 PET/MRI or Y-90 SPECT/CT. |
The Baseline CT/MRI will be compared against the Post TheraSphere administration imaging (Y90-SPECT-CT, or Y90-PET-CT, or Y90-PET-MRI) to measure agreement in the lesion locations identified with the 2 imaging methods. The 3 categories to evaluate the agreement between Baseline CT/MRI and 99mTc-MAA are: Optimal (images match), Sub optimal (less than 50% matching), and Non optimal (images do not match at all). |
Baseline and Post TheraSphere Administration Imaging (up to Day 28) |
|
| Secondary |
Description of pre and post treatment tumour targeting by determination of the number of patients with similar tumour(s) location based on 99mTc-MAA (SPECT or SPECT/CT and location of tumour targeted by Y-90 using post-treatment(PET/CT or PET/MRI or SPEC |
99mTc-MAA SPECT-CT will be compared against the Post TheraSphere administration (Y90-SPECT-CT, or Y90-PET-CT, or Y90-PET-MRI) to measure agreement in the lesion locations identified with the 2 imaging methods. The 3 categories to report agreement between Baseline 99mTc-MAA SPECT-CT and TheraSphere (Y90-SPECT-CT, or Y90-PET-CT, or Y90-PET-MRI) are: Optimal (images match), Sub optimal (less than 50% matching), and Non optimal (images do not match at all). |
Pre-Treatment Administration (Baseline) and Post-Treatment Administration (up to Day 28) |
|
| Secondary |
Description of Portal Vein Thrombosis (PVT) targeting by determination of the number of patients with PVT at baseline that have the PVT targeted by 99mTc-MAA (SPECT or SPECT/CT), Y-90 (PET/CT or PET/MRI or SPECT/CT). |
Types of PVT will be classified according to the following scale: Vp0 Absent; Vp1 Presence or tumour thrombus distal to, but not in, the second-order branches of the portal vein; Vp2 Presence of tumour thrombus in first -order branches of the portal vein; Vp3 Presence of tumour thrombus in first-order branches of the portal vein; and Vp4 Presence of tumour thrombus in the main trunk of portal vein or a portal vein contralateral to the primary involved lobe (or both). In case of PVT (Vp1 to Vp4), the intensity of 99mTc-MAA and TheraSphere uptake on PVT (that is, greater activity than surrounding treated liver parenchyma) evaluated on 99mTc-MAA SPECT-CT, Y90-SPECT-CT, or Y90-PET-CT or Y90-PET-MRI imagings will be graded qualitatively as strong, weak or no uptake on PVT. |
Pre-Treatment Administration (Baseline) and Post-Treatment Administration (up to Day 28) |
|
| Secondary |
Determination of a correlation between tumour and normal tissue liver absorbed doses, determined with 99mTc-MAA (SPECT or SPECT/CT), with qualitative tumour response (CR or PR), OS and safety, respectively as Assessed by Cox Regression Analyses |
A Cox regression analysis of OS will be performed to assess the impact of the tumour and normal liver tissue absorbed doses. This will be done separately for absorbed doses calculated before treatment administration with 99mTc-MAA (SPECT or SPECT/ CT) and estimated with post-treatment TheraSphere Y90-PET-CT or Y90-PET-MRI. |
Baseline and Post 99mTc-MAA Imaging (up to Day 28) |
|
| Secondary |
Determination of a correlation between tumour and normal tissue liver absorbed doses, determined with Y-90 (PET/CT or PET/MRI), with qualitative tumour response (CR or PR), OS and safety, respectively. |
A logistic regression analysis of qualitative tumour/index lesion response (CR or PR) will be performed to assess the impact of the tumour/index lesion AD (i.e. the response variable is whether there was a response and the explanatory variable is the AD). This will be done separately for ADs from pre-procedural 99mTc-MAA (SPECT or SPECT/CT) and for post-procedural Y-90 PET/CT or PET/MRI. A Cox regression analyses of OS will be performed to assess the impact of the tumour ADs (i.e., the AD will be the explanatory variable). This will be done separately for AD by 99mTc-MAA (SPECT or SPECT/CT) and by post-treatment Y-90 PET/CT and/or PET/MRI. Logistic regression analyses of the occurrence of SAEs will be performed to assess the impact of the non-tumoural liver absorbed doses. This will be done separately for absorbed doses calculated before treatment administration with 99mTc-MAA (SPECT or SPECT/ CT) and estimated with post-treatment TheraSphere® Y90-PET-CT or Y90-PET-MRI |
Baseline and Post 99mTc-MAA Imaging (up to Day 28) |
|
| Secondary |
Determination of a correlation between tumour and normal tissue liver absorbed doses determined with 99mTc-MAA (SPECT or SPECT/CT) and with Y-90 (PET/CT or PET/MRI) |
The relationship between absorbed doses derived from pre-procedural 99mTc-MAA (SPECT or SPECT/CT) imaging and post-treatment Y90 PET/CT or PET/MRI imaging will be assessed separately for normal tissue liver absorbed doses and tumour absorbed doses using Bland-Altman analysis. |
Baseline and Post 99mTc-MAA Imaging (up to Day 28) |
|
| Secondary |
Determination of a correlation between Dose volume histogram (DVH) for total perfused tumour, Index lesion and whole normal liver tissue, using 99mTc-MAA (SPECT or SPECT/CT) and Y-90 (PET/CT or PET/MRI). |
The DVH using 99Tc-MAA and TheraSphere (Y90-SPECT-CT, Y90-PET-CT, or Y90-PET-MRI) will be reported for total perfused tumours, index lesions, and whole normal liver tissues. The observed counts will be presented. A linear regression of AD from pre-procedural 99mTc-MAA (SPECT or SPECT/CT) imaging and post-procedural Y-90 PET/CT or PET/MRI imaging will be performed and Pearson's correlation coefficient will be calculated. |
Baseline and Post 99mTc-MAA Imaging (up to Day 28) |
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