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A TheraSphere® Advanced Dosimetry Retrospective Global Study in HCC (TARGET)

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ClinicalTrials.gov Identifier: NCT03295006
Recruitment Status : Recruiting
First Posted : September 27, 2017
Last Update Posted : April 3, 2019
Sponsor:
Information provided by (Responsible Party):
BTG International Inc.

Tracking Information
First Submitted Date June 29, 2017
First Posted Date September 27, 2017
Last Update Posted Date April 3, 2019
Actual Study Start Date October 31, 2016
Estimated Primary Completion Date November 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: September 22, 2017)
Alternative two-compartment TheraSphere dosimetry methodology [ Time Frame: Baseline ]
Normal tissue absorbed dose using pre-procedural 99mTc MAA (Technetium-99m Macroaggregated albumin) SPECT (Single-photon emission computer tomography) or SPECT/CT (Single-photon emission computer tomography/Computer Tomography) imaging, to allow the mean absorbed normal tissue dose corresponding to a ≤15% probability of Common Toxicities Criteria for Adverse Events (CTCAE) grade 3 or higher hyperbilirubinemia (in the absence of disease progression) to be calculated.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: April 1, 2019)
  • Tumor dose [ Time Frame: Baseline ]
    Tumor dose (to tumors ≥3 cm) using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging.
  • Serious adverse events [ Time Frame: 3 months ]
    All serious adverse events (SAEs) assessed as related or potentially related to TheraSphere
  • Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere [ Time Frame: 3 months ]
    Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere, comprising of any of the following events:
    • Hyperbilirubinemia
    • Ascites
    • Pain
    • Fatigue
    • Nausea
  • Clinical laboratory assessments [ Time Frame: 6 weeks and 3 months ]
    Clinical laboratory assessments
  • Objective response (OR) of the target lesion and non-target sesions [ Time Frame: 3 months and 6 months ]
    Objective response (OR) of the target lesion (single largest lesion) and non-target lesion(s) at 3 months and 6 months (if available), and for all scans up to 400 days after TheraSphere administration by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Volume changes [ Time Frame: 3 and 6 months ]
    Volume changes (i.e., perfused liver volume and non-perfused liver volume) from baseline afterTheraSphere administration.
  • Overall Survival (OS) [ Time Frame: 6 months ]
    Overall Survival (OS)
  • Target Alpha fetoprotein (AFP) response [ Time Frame: 6 weeks and 3 months ]
    Target Alpha fetoprotein (AFP) response (defined as a ≥50% decrease in AFP levels for patients with a baseline AFP level of ≥200 ng/mL).
  • Albumin-bilirubin (ALBI) score [ Time Frame: 6 weeks and 3 months ]
    Albumin-bilirubin (ALBI) score, a measure of liver function for HCC patients after TheraSphere administration.
  • Dose to Portal Vein Thrombosis (PVT) [ Time Frame: baseline, 90 days, 180 days ]
    Dose to Portal Vein Thrombosis (PVT) based upon pre- and postprocedure imaging (if PVT present).
  • Dosimetric analysis time [ Time Frame: baseline ]
    Dosimetric analysis time (i.e., workflow).
  • Dose accuracy [ Time Frame: baseline ]
    Dose accuracy based upon phantom imaging studies.
  • Dose reproducibility [ Time Frame: baseline ]
    Measurement of inter-observer agreement based on a round robin review of the same 20 patients obtained from a minimum of 8 users (with each user at a different site) and an exploratory assessment of intra-observer agreement based on a review of 10 patients by a minimum of 8 users at least 2 weeks apart. The 10 patients for the intra-observer agreement will be a subset of the patients included in the assessment of inter-observer agreement.
Original Secondary Outcome Measures
 (submitted: September 22, 2017)
  • Tumor dose [ Time Frame: Baseline ]
    Tumor dose (to tumors ≥3 cm) using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging.
  • Serious adverse events [ Time Frame: 3 months ]
    All serious adverse events (SAEs) assessed as related or potentially related to TheraSphere
  • Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere [ Time Frame: 3 months ]
    Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere, comprising of any of the following events:
    • Hyperbilirubinemia
    • Ascites
    • Pain
    • Fatigue
    • Nausea
  • Clinical laboratory assessments [ Time Frame: 6 weeks and 3 months ]
    Clinical laboratory assessments
  • Objective response (OR) of the target lesion and non-target sesions [ Time Frame: 3 months and 6 months ]
    Objective response (OR) of the target lesion (single largest lesion) and non-target lesion(s) after TheraSphere administration by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
  • Volume changes [ Time Frame: 3 and 6 months ]
    Volume changes (i.e., perfused liver volume and non-perfused liver volume) from baseline afterTheraSphere administration.
  • Overall Survival (OS) [ Time Frame: 6 months ]
    Overall Survival (OS)
  • Target Alpha fetoprotein (AFP) response [ Time Frame: 6 weeks and 3 months ]
    Target Alpha fetoprotein (AFP) response (defined as a ≥50% decrease in AFP levels for patients with a baseline AFP level of ≥200 ng/mL).
  • Albumin-bilirubin (ALBI) score [ Time Frame: 6 weeks and 3 months ]
    Albumin-bilirubin (ALBI) score, a measure of liver function for HCC patients after TheraSphere administration.
  • Dose to Portal Vein Thrombosis (PVT) [ Time Frame: baseline, 90 days, 180 days ]
    Dose to Portal Vein Thrombosis (PVT) based upon pre- and postprocedure imaging (if PVT present).
  • Dosimetric analysis time [ Time Frame: baseline ]
    Dosimetric analysis time (i.e., workflow).
  • Dose accuracy [ Time Frame: baseline ]
    Dose accuracy based upon phantom imaging studies.
  • Dose reproducibility [ Time Frame: baseline ]
    Measurement of inter-observer agreement based on a round robin review of the same 20 patients obtained from a minimum of 8 users (with each user at a different site) and an exploratory assessment of intra-observer agreement based on a review of 10 patients by a minimum of 8 users at least 2 weeks apart. The 10 patients for the intra-observer agreement will be a subset of the patients included in the assessment of inter-observer agreement.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title A TheraSphere® Advanced Dosimetry Retrospective Global Study in HCC
Official Title A TheraSphere® Advanced Dosimetry Retrospective Global Study Evaluation in Hepatocellular Carcinoma Treatment
Brief Summary This retrospective, multinational, single-arm study will be conducted in at least 8 sites. An interim analysis will be conducted with data from 100 patients with up to 10 well defined HCC tumor(s) and with at least one tumor ≥3 cm. Normal tissue absorbed dose using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging will be measured to allow the mean absorbed normal tissue dose corresponding to a ≤15% probability of CTCAE grade 3 or higher hyperbilirubinemia (in the absence of disease progression) to be calculated. Total bilirubin will be recorded and graded according to CTCAE version 4.02. All dose-related SAEs at 3 months follow-up will be followed until resolution, death or lost-to-follow-up. AEs related to disease progression will not be considered related to TheraSphere.
Detailed Description Recently published evidence indicates a correlation between yttrium-90 dose delivered to the tumor and normal tissue with safety and efficacy outcomes but there are no validated methods to consistently measure dose delivered to the tumor and normal tissue. In contrast to the standard clinical approach based on average dose to one target volume, this trial, sponsored by Biocompatibles UK, will explore an alternative two-compartment TheraSphere dosimetry methodology to calculate absorbed dose to tumor and normal tissue
Study Type Observational
Study Design Observational Model: Other
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Patients with up to 10 well-defined unilobar HCC tumors per lobe with at least one tumor ≥3 cm ± PVT.
Condition Hepatocellular Carcinoma
Intervention Device: TheraSphere
Patients who had received TheraSphere
Study Groups/Cohorts Previous Therasphere treatment
Patients who had received TheraSphere yttrium-90 microspheres
Intervention: Device: TheraSphere
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: September 22, 2017)
300
Original Estimated Enrollment Same as current
Estimated Study Completion Date November 30, 2019
Estimated Primary Completion Date November 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Up to 10 well defined unilobar/bilobar HCC tumor(s) per lobe with at least one tumor ≥3 cm ± PVT
  • Liver dominant disease (limited extra-hepatic metastases in the lung and/or lymph nodes are permitted (up to 5 lesions in the lung, with each individual lesion ≤2cm; any number of lymph node lesions with each individual lesion ≤2 cm).
  • Child Pugh stage A or B7.
  • BCLC A, B or C.
  • Must be male or female, 18 years of age or older.
  • Bilirubin ≤2 mg/dL.
  • Tumor replacement <50% of total liver volume assessed by diagnostic imaging consisting of multi-phase contrast enhanced CT or contrast enhanced MRI.
  • Diagnostic imaging consisting of multi-phase contrast enhanced CT or contrast enhanced MRI within 3 months prior to TheraSphere® administration.
  • Infusion of 99mTc-MAA in a single arterial location sufficient to cover up to 10 well-defined tumors per lobe ≤ 6 weeks prior to TheraSphere® administration.
  • Patients must have received TheraSphere® in a single treatment setting in one or more arterial locations sufficient to cover up to 10 well-defined tumors based on angiography. Subsequent TheraSphere® treatment to the second lobe may occur at least 4 weeks following the initial TheraSphere® treatment.
  • For patients receiving a second TheraSphere® treatment bilirubin levels must have been recorded prior to the second treatment
  • Patients must have had clinical evaluation (assessment of liver specific AEs) and laboratory evaluation (at least a serum bilirubin level) at baseline.
  • Tumor(s), ≥3 cm, measurable by mRECIST and RECIST 1.1 at baseline

Exclusion Criteria:

  • Prior external beam radiation treatment to the liver.
  • Prior loco-regional liver directed therapy (cTACE, DEB-TACE and SIR-Spheres).
  • Prior liver transplantation.
  • Whole liver TheraSphere® treatment following prior liver resection.
  • TheraSphere administration to ≤2 segments (e.g., radiation segmentectomy).
  • Additional active therapy (TACE and treatment with SIR-Spheres) between first TheraSphere treatment and 3 month (90 days) imaging.
  • Hepatic vein invasion.
  • Diagnosis of disease progression at peri-procedural imaging as compared to the baseline imaging (physician's discretion).
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts
Contact: Frances Harrison 610-278-1660 frances.harrison@btgplc.com
Listed Location Countries France,   Germany,   Italy,   Netherlands,   Saudi Arabia,   Switzerland,   Turkey,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT03295006
Other Study ID Numbers BTG-007961
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party BTG International Inc.
Study Sponsor BTG International Inc.
Collaborators Not Provided
Investigators
Principal Investigator: Marnix Lam, MD, PhD Universitair Medisch Centrum Utrecht
Principal Investigator: Riad Salem, MD Northwestern University
Principal Investigator: Etienne Garin, MD Centre Eugène Marquis
Principal Investigator: Hugo de Jong, PhD Universitair Medisch Centrum Utrecht
PRS Account BTG International Inc.
Verification Date April 2019