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Evaluating the Effectiveness of Yttrium-90 Glass Microspheres in the Treatment of Hepatocellular Carcinoma, Intrahepatic Cholangiocarcinoma, and Metastatic Colorectal Cancer in Practice: Protocol for the Prospective PROACTIF Phase IV Registry Study in France

  • Study Protocol
  • INTERVENTIONAL ONCOLOGY
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Abstract

Primary Objective

Recently, selective internal radiation therapy using yttrium-90 (Y90) glass microspheres (TheraSphere™) was approved for reimbursement by health authorities in France. The PROACTIF study aims to gather data on effectiveness, patient quality of life, and safety with use of Y90 glass microspheres in real-world clinical settings in France.

Inclusion Criteria

Patient with a diagnosis of hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCC), and/or metastatic colorectal cancer (mCRC) who was treated with a dose of Y90 glass microspheres that has been reimbursed in France and who do not oppose use of their personal medical data.

Exclusion Criteria

If data collection is opposed, treatment is reimbursed but not administered, or treatment is administered but not reimbursed.

Outcome Measures

Primary outcome measures include overall survival from time of Y90 glass microsphere treatment and quality of life, as assessed using the Functional Assessment of Cancer Therapy- Hepatobiliary questionnaire.

Estimated Number of Patients to Be Included

This is an open study and there is no set number of patients; 115 have already been enrolled.

Planned Subgroup Analyses

Analyses will be stratified by disease state (HCC, iCC, or mCRC). Subgroups to be analyzed include age group, unilobar/bilobar disease at baseline, Eastern Cooperative Oncology Group (ECOG) status at baseline, liver tumor burden at baseline, target lesion size, and standard versus multi-compartment personalized dosimetry treatment.

Planned Recruitment and Observation Period

Recruitment includes patients who are prescribed and treated with a commercial vial of Y90 glass microspheres between 01 January 2019 and 31 December 2024.

Trial registration

ClinicalTrials.gov Identifier: NCT04069468.

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Abbreviations

HCC:

Hepatocellular carcinoma

iCC:

Intrahepatic cholangiocarcinoma

mCRC:

Metastatic colorectal cancer

SIRT:

Selective internal radiation therapy

BCLC:

Barcelona clinic liver cancer

Y90:

Yttrium-90

PROACTIF:

A prospective, post approval, multiple centre, open-label, non- interventional, registry study to evaluate effectiveness of therasphere in clinical practice in France

QoL:

Quality of life

RIHP3:

Recherche impliquant la personne humaine de categorie 3

FACT-Hep:

Functional assessment of cancer therapy – hepatobiliary cancer

Bq:

Becquerel

EDC:

Electronic data capture

PIS:

Patient information sheet

GDPR:

General data protection regulation

eCRF:

Electronic case report form

PVT:

Portal vein thrombosis

99mTc-MAA:

Technetium albumin aggregated

SPECT:

Single-photon emission computed tomography

CT:

Computed tomography

IFU:

Instructions for use

ALT:

Alanine aminotransferase

AST:

Aspartate aminotransferase

INR:

International normalized ratio

AFP:

Alpha-fetoprotein

CA19-9:

Carbohydrate antigen 19-9

CEA:

Carcinoembryonic antigen

MRI:

Magnetic resonance imaging

RECIST 1.1:

Response evaluation criteria in solid tumors

mRECIST:

Modified response evaluation criteria in solid tumors

MCD:

Multi-compartment dosimetry

PET:

Positron emission tomography

OS:

Overall survival

SAEs:

Serious adverse events

AEs:

Adverse events

NCI-CTCAE:

National cancer institute common terminology criteria for adverse events

CR:

Complete response

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

DVH:

Dose volume histogram

ECOG:

Eastern cooperative oncology group

ALBI:

Albumin-bilirubin

CI:

Confidence interval

FOLFOX:

Folinic acid, fluorouracil, and oxaliplatin

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Acknowledgements

The authors wish to acknowledge Carole Allimant, MD, for performing blinded centralized dosimetric assessments, and Alexandra Greenberg-Worisek, PhD, MPH (Boston Scientific Corporation) for medical writing assistance.

Funding

The PROACTIF Registry study is funded by Biocompatibles/Boston Scientific Corporation. The funding body provided support in the analysis of data and in providing medical writing support for the manuscript.

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Corresponding author

Correspondence to Boris Guiu.

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Conflict of interest

E.G.: Received fees and a grant from BTG Ltd./Boston Scientific Corporation. J.P.: Nothing to disclose. C.B.: Nothing to disclose. C.S.: Nothing to disclose. D.M-G.: Nothing to disclose. J.E.: Received fees and support for research from Boston Scientific; consultant for Roche, AstraZeneca, MSD, BMS, Eisai, Bayer, and Ipsen. J-F.B: Consultant for Bayer, Astra-Zeneca, IPSEN, ESAI, Roche, and BMS. A.B.: Nothing to disclose. J.T.: Nothing to disclose. A.R: Nothing to disclose. S.B.: Nothing to disclose. D.S.: Nothing to disclose. T. de B.: Consultant for Boston Scientific Corporation, Guerbet, GE-Healthcare, HD Technologies, Terumo, Astra-Zeneca, and Eisai; speaker for Boston Scientific Corporation, Guerbet, GE-Healthcare, HD Technologies, and Terumo. C. S-D: Nothing to disclose. C.M.: Nothing to disclose. J.G.: Nothing to disclose. P.C.: Nothing to disclose. H.R.: Consultant for Boston Scientific Corporation. E.V.: Received fees for methodological consulting from Biocompatibles UK Ltd. S.M.: Nothing to disclose. E.V.: Receives fees from Bayer, BMS, Johnson & Johnson, and Boston Scientific Corporation; serves as consultant for Nanobiotix; academic collaboration with EchoSens, Fluoptics, and IntraSence. B.P.: Employee of Biocompatibles/Boston Scientific Corporation. E.B.: Employee of Biocompatibles/Boston Scientific Corporation. B.G.: Consultant for Boston Scientific, Quantum Surgical, Terumo. Received research grant from Roche, Guerbet.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was classified in France as Recherche Impliquant la Personne Humaine de Catégorie 3 (RIHP 3) by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM) due to its observational, non-interventional design. The protocol was approved by a randomly assigned to one of the 39 Independent Ethics Committees in France prior to the study’s initiation (assigned to French Ethics Committee « Ile de France VII»); assignments are made by the French National Commission for Research Involving Human Persons (CNRIPH).

Informed Consent

Patients will receive a Patient Information Sheet (PIS), which they will be able to review prior to treatment and about which patients will be given the opportunity to ask questions of the investigator or delegate. As detailed by the General Data Protection Regulation (GDPR) and requested by the ethics committee, this PIS will inform the patient about the purpose and aim of the registry and how their personal medical data will be used. After reviewing this sheet, clinicians will document whether the patient expresses verbal non-opposition to data collection in the patient’s record (“non-opposition to data collection”).

Consent for Publication

Consent for publication was obtained for every individual person’s data included in the study.

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*All members of PROACTIF Registry Group listed in Supplementary Material A.

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Garin, E., Pinaquy, JB., Bailly, C. et al. Evaluating the Effectiveness of Yttrium-90 Glass Microspheres in the Treatment of Hepatocellular Carcinoma, Intrahepatic Cholangiocarcinoma, and Metastatic Colorectal Cancer in Practice: Protocol for the Prospective PROACTIF Phase IV Registry Study in France. Cardiovasc Intervent Radiol 45, 1–11 (2022). https://doi.org/10.1007/s00270-021-03002-0

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