Internal Radiation Therapy for Hepatocellular Carcinomas With Therasphere: Optimized Dosimetry Versus Standard Dosimetry

January 30, 2019 updated by: Center Eugene Marquis

Selective Internal Radiation Therapy for Hepatocellular Carcinomas With Yttrium-90 Loaded Microspheres: Optimized Dosimetry Versus Standard Dosimetry

The purpose of this study is to determine whether a treatment with Therasphere which is optimized is more efficient compared to a standard treatment for patients suffering from hepatocellular carcinomas.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

For patients suffering from hepatocellular carcinoma, a palliative treatment can be proposed if tumor expansion is limited to the liver. One of palliative treatment is the the Selective Internal Radiation Therapy (SIRT) with Therasphere®. This treatment is made secure by performing a diagnostic angiogram coupled with a hepatic perfusion scintigraph with which patients at risk of complications are identified and excluded. The treatment objective, with the standard dosimetric approach, is to deliver an absorbed dose of 120 ± 20 Gy to the treated hepatic volume, most often one lobe. Recent retrospective trials show that an optimized dosimetric approach, considering the dose absorbed by the tumor, is technically achievable and would probably make it possible to obtain a better effectiveness. In our experience, treatment personalisation have been described to be used for 60% of the patients with a tumor larger than 7 cm underlying the clinical impact of this new approach.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Créteil, France, 94000
        • CHU Henri Mondor
      • Montpellier, France, 34925
        • Chu Saint Eloi
      • Rennes, France, 35042
        • Centre Eugène Marquis
      • Villejuif, France
        • Gustave Roussy

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age ≥ 18,
  • Written free and informed consent,
  • Histologically demonstrated Hepatocellular Carcinoma (HCC), not a candidate for surgery or local ablative treatment (radio frequency, etc.)
  • Barcelona Clinic Liver Cancer (BCLC) classification A, B or C,
  • At least one lesion ≥ 7 cm,
  • Hepatic reserve (hepatic parenchyma not treated) after the first SIRT ≥ 30%,
  • Unilateral involvement, minimal bilateral involvement allowed only with a hepatic reserve ≥ 30% after SIRT
  • Child A classification only, or B but with bilirubinemia <35 micromol/L,
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1,

  • Patients whose biological parameters meet the following criteria:

    • Hemoglobin ≥ 8.5 g/dL,
    • Granulocytes ≥ 1500/mm3,
    • Platelets ≥ 50,000/mm3,
    • Bilirubinemia <35 micromol per liter,
    • Transaminases ≤ five times the upper limit of normal,
    • Creatininemia ≤ 1.5 times the normal upper limit,
  • Expected survival over 12 weeks,
  • Negative pregnancy test for women of childbearing age,
  • If sorafenib has been taken the diagnostic angiogram must follow it by at least four weeks after its stop.

Exclusion Criteria:

  • HCC operable or accessible to a local ablative treatment (radio frequency),
  • Hepatectomy history unless a segmental treatment is considered, with a hepatic reserve ≥ 30% after SIRT,
  • Prior treatment with sorafenib unless stopped at least four weeks earlier,
  • History of chemo-embolization of the principal lesion, except in case of nodular residual lesion measuring at least 7 cm or in case of progression after initial response,
  • Bilateral disease requiring a whole liver injection or with a hepatic reserve < 30% after SIRT
  • Treatment of another cancer less than one year earlier,
  • Extra-hepatic metastases other than adenopathies of the hilum smaller than 2 cm,
  • >70% tumor invasion of the liver,
  • Bilirubinemia ≥ 35 µmol/L,
  • A Severe underlying biliary pathology:
  • Bile duct anomaly (stent, dilation) Cirrhosis of biliary origin,
  • Women of childbearing age without contraception
  • Pregnant or nursing women

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Standard dosimetry
Standard Internal Radiation Therapy : Dose of radiation delivered to the tumoral volume is fixed : 120 Gray (GY)
Radiation: Standard Internal Radiation Therapy

Injection of yttrium-90 microspheres (TheraSphere®) is performed during the therapeutic angiogram, directly into the hepatic artery (left or right, or even segmental).Standard dosimetry arm: the activity to be administered is calculated so as predictive dosimetry:

  • An absorbed dose of 120 ± 20 Gy to the treated volume (whatever the tumor absorbed dose)
  • A pulmonary dose < 30 Gy for one treatment and < 50 Gy in cumulative dose in case of multiple treatments.
Experimental: Optimized dosimetry
Optimized Internal Radiation Therapy : Dose of radiation absorbed by the tumor is > 205 GY, if possible 250 or 300 Gy.
Radiation: Optimized Internal Radiation Therapy

Injection of yttrium-90 microspheres (TheraSphere®) is performed during the therapeutic angiogram, directly into the hepatic artery (left or right, or even segmental).

Optimized dosimetry arm: the activity to be administered is calculated so as to deliver predictive dosimetry:

  • An absorbed dose to the tumor of at least ≥ 205 Gy and if possible exceeding 250 Gy or even 300 Gy
  • A dose at the treated healthy liver < 120 Gy in case of lobar treatment
  • Dose to the treated healthy liver can exceed 120 Gy in case of segmental treatment and hepatic reserve > 30%
  • A pulmonary dose < 30 Gy for one treatment and < 50 Gy in cumulative dose in case of multiple treatments.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The primary endpoint is to compare the response rate of the treated lesion at the first radioembolization, evaluated using European Association for the Study of the Liver (EASL) criteria of yttrium-90 marked glass microspheres SIRT
Time Frame: 3 months after treatment administration
3 months after treatment administration

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival
Time Frame: Up to 12 months
Up to 12 months
Overall survival
Time Frame: Up to 30 months after inclusion of the 1st patient
Up to 30 months after inclusion of the 1st patient
Related Adverse Events in both arms as assessed by National Cancer Institute criteria (National Cancer Institute Common Terminology Criteria for Adverse Events, (NCI CTCAE) version 4).
Time Frame: Up to 12 months
Up to 12 months
Progression free survival not accessible to SIRT
Time Frame: Up to 12 months after treatment administration
Up to 12 months after treatment administration
Post-therapeutic dosimetry measured by Positron emission tomography-computed tomography PET / CT
Time Frame: Day one of treatment administration
Dose delivered to the treated liver, the tumors, healthy liver and lings
Day one of treatment administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Center Eugene Marquis

Investigators

  • Study Chair: Etienne GARIN, Pr, Centre Eugène Marquis

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2015

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

December 1, 2018

Study Registration Dates

First Submitted

October 9, 2015

First Submitted That Met QC Criteria

October 19, 2015

First Posted (Estimate)

October 21, 2015

Study Record Updates

Last Update Posted (Actual)

January 31, 2019

Last Update Submitted That Met QC Criteria

January 30, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DOSISPHERES-01

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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