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Non-Interventional Registry Study to Evaluate the Effectiveness of TheraSphere® in the Treatment of Hepatocellular Carcinoma (HCC) (PROACTIF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04069468
Recruitment Status : Recruiting
First Posted : August 28, 2019
Last Update Posted : February 5, 2020
Sponsor:
Information provided by (Responsible Party):
Biocompatibles UK Ltd

Brief Summary:
The purpose of this registry study is to gather effectiveness, QoL, safety and procedural information on TheraSphere® for the treatment of participants with HCC in real world clinical practice settings in France.

Condition or disease Intervention/treatment
Hepatocellular Carcinoma Device: TheraSphere

Detailed Description:

TheraSphere® is a radioembolic therapeutic device used in the treatment of liver cancers. The goal of the registry study is to collect prospectively: participant description, treatment goal, treatment description, treatment results, safety, quality of life and survival data to ultimately demonstrate that TheraSphere® treatment meets the claims that led to the reimbursement in France. The registry study is also an opportunity to improve the proper use of the device by team training especially for the personalized dosimetry treatment approach.

Clinical data will be collected and held in a secured, validated system and can be downloaded by BTG Data Management on an ongoing basis. Data verification will be performed by BTG Data Management and data validation checks will be created by the validated data system (with the BTG team performing User Acceptance Testing on them before they go live). Adverse Events and concomitant diseases will be coded according to the version of Medical Dictionary for Regulatory Activities (MedDRA) agreed with Biocompatibles UK Ltd. Concomitant medications will be coded using the version of the World Health Organisation (WHO) Drug dictionary agreed with the validated data system.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 500 participants
Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration: 6 Years
Official Title: A Prospective, Post Approval, Multiple Centre, Open-Label, Non-Interventional, Registry Study to Evaluate Effectiveness of TheraSphere® in Clinical Practice in France
Actual Study Start Date : March 13, 2019
Estimated Primary Completion Date : January 1, 2024
Estimated Study Completion Date : January 1, 2025

Resource links provided by the National Library of Medicine


Group/Cohort Intervention/treatment
TheraSphere®
TheraSphere® will be administered through the hepatic artery. Activity of administered TheraSphere® is tailored in order to deliver an absorbed dose of 80 to150 gray (Gy) to the liver without exceeding 50 Gy cumulatively in the lungs. Lung dose (D) will be calculated from the following formula: D=A*(1-S)*50/1. D=Planned dose absorbed by treated volume(Gy), A=Activity injected with microspheres (gigabequerel [GBq]), S=Percentage of pulmonary shunt, "1" assuming that the lung mass=1 kilograms [kg]). Number of treatments is up to Investigator's discretion. If 2 treatments are required to complete treatment, the lobe with the highest tumour burden should be scheduled for 1st treatment. Before the 2nd treatment session, a 2nd angiogram with 99mTc-MAA scan should be performed. A 2nd treatment would typically take place 30-45 days after 1st treatment, provided participant has tolerated 1st treatment. Treatment will be performed according to the Instructions for Use (IFU).
Device: TheraSphere
Participants will receive treatment with TheraSphere in accordance with Instructions for Use
Other Name: Yttrium-90 Glass Microspheres




Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Treatment (Day 1) up to participant's death, opposition to data collection, or study termination (up to Year 6) ]
    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.

  2. QoL Measurements Using FACT-HEP Questionnaire Before and After Treatment [ Time Frame: 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) ]
    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.


Secondary Outcome Measures :
  1. Number of Grade 3 or Higher Adverse Events (AEs) Related to Study Procedure [ Time Frame: Treatment (Day 1) up to 90 Days Post Treatment (maximum treatment time = up to Day 28) ]
    An AE is any untoward medical occurrence or undesirable event experienced in a participant that begins or worsens following TheraSphere® administration. An undesirable event can be, but is not limited to, objective findings or symptoms experienced by a participant, such as significant clinical laboratory abnormalities. AEs will be classified using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v 5.0 (Grade 1=mild, Grade 2=moderate, Grade 3=severe or medically significant but not immediately life-threatening, Grade 4=life-threatening consequences, and Grade 5=death related to AE). Grade 3 or higher AEs related or possibly related to the device, or the device administration procedure that occur up to the second follow-up visit (or within a minimum of 90 days) after last TheraSphere® administration will be reported. A summary of other non-serious AEs and all serious AEs (SAEs), regardless of causality will be located in the 'Reported AE section'.

  2. Number of Participants Re-Hospitalised Following Treatment [ Time Frame: Treatment (Day 1) up to Month 1 Post Treatment (maximum treatment time = up to Day 28) ]
    The number of participants re-hospitalised for any event related to TheraSphere® treatment during the study will be reported.

  3. Duration of Re-Hospitalisations Following Treatment [ Time Frame: Treatment (Day 1) up to Month 1 Post Treatment (maximum treatment time = up to Day 28) ]
    The duration of re-hospitalisations for any event related to TheraSphere® treatment during the study will be reported.

  4. Number of Participants Achieving Treatment Expectation [ Time Frame: Baseline up to Month 12 Post Treatment ]
    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 proposals are: improvement of tumour symptoms, obtain a Complete Response, obtain a Partial Tumour Response, obtain a Disease Control response, improve portal vein thrombosis [PVT] extension, control tumour symptoms, improve survival, improve QoL, downsize to surgery, bridge to liver transplantation, and contralateral lobe hypertrophy). The number of participants achieving the treatment goal will be reported.

  5. Number of Participants with Tumour Response [ Time Frame: Treatment (Day 1) up to Month 12 Post Treatment (maximum treatment time = up to Day 28) ]
    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: CR=disappearance of any intratumoural arterial enhancement in all target lesions; PR=≥30% decrease in the sum of diameters of viable target lesions; SD=neither CR, PR, PD; and PD=≥20% increase in the sum of the diameter of viable of target lesion and/or appearance of new lesion intra or extra hepatic.

  6. Number of Participants with an Alpha-Fetoprotein (AFP) Response [ Time Frame: Treatment (Day 1) and Month 12 Post Treatment (maximum treatment time = up to Day 28) ]
    An AFP response defined as a ≥50% decrease in AFP levels for participants with a Baseline AFP level ≥200 nanograms/milliliter (ng/mL).

  7. Number of Participants Receiving a Post TheraSphere Anti-Cancer Treatment [ Time Frame: Treatment (Day 1) up to participant's death, opposition to data collection, study withdraw for any cause, or study termination (up to Year 6) ]
    The number of participants for which additional TheraSphere® treatment or surgical procedure is required will be reported.

  8. Number of Participants Reporting Best Supportive Care Treatment [ Time Frame: Treatment (Day 1) up to participant's death, opposition to data collection, study withdraw for any cause, or study termination (up to Year 6) ]
    The number of participants for which additional anti-cancer treatment including additional TheraSphere® treatment or surgical procedure will be reported.

  9. Number of Participants with Agreement of Tumour Location Between the Baseline CT/MRI and Technetium-99m Macroaggregated albumin (99mTc-MAA) Imaging [ Time Frame: Baseline and Post 99mTc-MAA Imaging (up to Day 28) ]
    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% of tumour coverage), and Non optimal (images do not match at all).

  10. Number of Participants with Agreement of Lesion Location with the Baseline CT/MRI and Post TheraSphere® Administration Imaging [ Time Frame: Baseline and Post TheraSphere Administration Imaging (up to Day 28) ]
    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 at the 2 timepoints. The 3 categories to evaluate the agreement between Baseline CT/MRI and 99mTc-MAA are: Optimal (images match), Sub optimal (less than 50% of tumour coverage), and Non optimal (images do not match at all).

  11. Number of Participants with Agreement of Lesion Location with the 99mTc-MAA and Post TheraSphere® Administration Imaging (Y90-SPECT-CT, or Y90-PET-CT, or Y90-PET-MRI) [ Time Frame: Pre-Treatment Administration (Baseline) and Post-Treatment Administration (up to Day 28) ]
    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 at the 2 timepoints. 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% of tumour coverage), and Non optimal (images do not match at all).

  12. Number of Participants with Agreement of PVT at Baseline (CT or MRI) and Targeting Agreement of PVT by 99mTc-MAA (99mTc-MAA SPECT-CT ) and by TheraSphere® (Y90-SPECT-CT, Y90-PET-CT, or Y90-PET-MRI) [ Time Frame: Pre-Treatment Administration (Baseline) and Post-Treatment Administration (up to Day 28 ]
    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 PVT targeted by 99mTc-MAA and TheraSphere® (that is, greater activity than surrounding treated liver parenchyma) on 99mTc-MAA SPECT-CT, Y90-SPECT-CT, or Y90-PET-CT or Y90-PET-MRI imagings will be graded qualitatively.

  13. OS as Assessed by Cox Regression Analyses [ Time Frame: Treatment (Day 1) up to participant's death, opposition to data collection, study withdraw for any cause, or study termination (up to Year 6) ]
    A Cox regression analysis of OS will be performed to assess the impact of the tumour 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.

  14. Occurrence of SAEs as Assessed by Logistic Regression Analyses [ Time Frame: Treatment (Day 1) up to Day 28 ]
    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.

  15. Absorbed Doses in Non-Tumoural Livers and Tumours as Assessed by Bland-Altman Analysis [ Time Frame: Treatment (Day 1) up to Day 28 ]
    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 non-tumoural liver absorbed doses and tumour absorbed doses using Bland-Altman analysis.

  16. Number of Participants per Type of Vascular Access Used to Administer TheraSphere® [ Time Frame: Treatment (Day 1) up to Month 12 ]
    The number of participants recorded for each type of vascular access (that is, Femoral/Radial-Humeral) will be reported.

  17. The Dose Volume Histogram (DVH) Profile of the Total Perfused Tumor, the Index Lesion, and the Whole Normal Liver Using 99mTc-MAA and TheraSphere® (Y90-SPECT-CT, Y90-PET-CT, or Y90-PET-MRI) [ Time Frame: Treatment (Day 1) up to Day 28 ]
    The DVH using 99MTC-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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All participants for whom treatment with TheraSphere® has been prescribed and reimbursed in France will be eligible for this study. It is estimated that data from >500 participants will be entered into this registry from approximately 30 sites in France.
Criteria

Inclusion:

  • Participant has received a reimbursed dose of TheraSphere®
  • Participant does not oppose to the collection of his/her medical personal data

Exclusion:

  • Participant has opposed to data collection
  • Participant has not received a reimbursed dose of TheraSphere® (free of charge dose)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04069468


Contacts
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Contact: Boris Guiu 33 630 579 149 b-guiu@chu-montpellier.fr

Locations
Show Show 27 study locations
Sponsors and Collaborators
Biocompatibles UK Ltd
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Responsible Party: Biocompatibles UK Ltd
ClinicalTrials.gov Identifier: NCT04069468    
Other Study ID Numbers: BTG-007996-01
First Posted: August 28, 2019    Key Record Dates
Last Update Posted: February 5, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Biocompatibles UK Ltd:
Prospective Registry
TheraSphere®
France
SIRT
Liver Cancer, Adult
Liver Cell Carcinoma
Hepatoma
Intra arterial treatment
Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases