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

Primary Purpose

Adenoma, Liver Cell

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Optimized Internal Radiation Therapy
Standard Internal Radiation Therapy
Sponsored by
Center Eugene Marquis
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adenoma, Liver Cell focused on measuring Optimized Dosimetry versus standard Dosimetry, Internal Radiation Therapy

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • CHU Henri Mondor
  • CHU Saint Eloi
  • Centre Eugène Marquis
  • Gustave Roussy

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Standard dosimetry

Optimized dosimetry

Arm Description

Standard Internal Radiation Therapy : Dose of radiation delivered to the tumoral volume is fixed : 120 Gray (GY)

Optimized Internal Radiation Therapy : Dose of radiation absorbed by the tumor is > 205 GY, if possible 250 or 300 Gy.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Progression Free Survival
Overall survival
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).
Progression free survival not accessible to SIRT
Post-therapeutic dosimetry measured by Positron emission tomography-computed tomography PET / CT
Dose delivered to the treated liver, the tumors, healthy liver and lings

Full Information

First Posted
October 9, 2015
Last Updated
January 30, 2019
Sponsor
Center Eugene Marquis
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1. Study Identification

Unique Protocol Identification Number
NCT02582034
Brief Title
Internal Radiation Therapy for Hepatocellular Carcinomas With Therasphere: Optimized Dosimetry Versus Standard Dosimetry
Official Title
Selective Internal Radiation Therapy for Hepatocellular Carcinomas With Yttrium-90 Loaded Microspheres: Optimized Dosimetry Versus Standard Dosimetry
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
December 2015 (Actual)
Primary Completion Date
December 2018 (Actual)
Study Completion Date
December 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Center Eugene Marquis

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Adenoma, Liver Cell
Keywords
Optimized Dosimetry versus standard Dosimetry, Internal Radiation Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
56 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Standard dosimetry
Arm Type
Active Comparator
Arm Description
Standard Internal Radiation Therapy : Dose of radiation delivered to the tumoral volume is fixed : 120 Gray (GY)
Arm Title
Optimized dosimetry
Arm Type
Experimental
Arm Description
Optimized Internal Radiation Therapy : Dose of radiation absorbed by the tumor is > 205 GY, if possible 250 or 300 Gy.
Intervention Type
Radiation
Intervention Name(s)
Optimized Internal Radiation Therapy
Intervention Description
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.
Intervention Type
Radiation
Intervention Name(s)
Standard Internal Radiation Therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Progression Free Survival
Time Frame
Up to 12 months
Title
Overall survival
Time Frame
Up to 30 months after inclusion of the 1st patient
Title
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
Title
Progression free survival not accessible to SIRT
Time Frame
Up to 12 months after treatment administration
Title
Post-therapeutic dosimetry measured by Positron emission tomography-computed tomography PET / CT
Description
Dose delivered to the treated liver, the tumors, healthy liver and lings
Time Frame
Day one of treatment administration

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Etienne GARIN, Pr
Organizational Affiliation
Centre Eugène Marquis
Official's Role
Study Chair
Facility Information:
Facility Name
CHU Henri Mondor
City
Créteil
ZIP/Postal Code
94000
Country
France
Facility Name
CHU Saint Eloi
City
Montpellier
ZIP/Postal Code
34925
Country
France
Facility Name
Centre Eugène Marquis
City
Rennes
ZIP/Postal Code
35042
Country
France
Facility Name
Gustave Roussy
City
Villejuif
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
33166497
Citation
Garin E, Tselikas L, Guiu B, Chalaye J, Edeline J, de Baere T, Assenat E, Tacher V, Robert C, Terroir-Cassou-Mounat M, Mariano-Goulart D, Amaddeo G, Palard X, Hollebecque A, Kafrouni M, Regnault H, Boudjema K, Grimaldi S, Fourcade M, Kobeiter H, Vibert E, Le Sourd S, Piron L, Sommacale D, Laffont S, Campillo-Gimenez B, Rolland Y; DOSISPHERE-01 Study Group. Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial. Lancet Gastroenterol Hepatol. 2021 Jan;6(1):17-29. doi: 10.1016/S2468-1253(20)30290-9. Epub 2020 Nov 7.
Results Reference
derived

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

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