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

NCT ID: NCT02582034

Last Updated: 2019-01-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 56 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2018-12-31

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.

Conditions

Adenoma, Liver Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard dosimetry

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

Group Type: ACTIVE_COMPARATOR

Standard Internal Radiation Therapy

Intervention Type: RADIATION

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.

Optimized dosimetry

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

Group Type: EXPERIMENTAL

Optimized Internal Radiation Therapy

Intervention Type: RADIATION

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: RADIATION

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Center Eugene Marquis

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Etienne GARIN, Pr

Role: STUDY_CHAIR

Centre Eugène Marquis

Locations

CHU Henri Mondor

Créteil, , France

CHU Saint Eloi

Montpellier, , France

Centre Eugène Marquis

Rennes, , France

Gustave Roussy

Villejuif, , France

Countries

France

References

Garin E, Tselikas L, Guiu B, Chalaye J, Rolland Y, de Baere T, Assenat E, Tacher V, Palard X, Deandreis D, Mariano-Goulart D, Amaddeo G, Boudjema K, Hollebecque A, Meerun MA, Regnault H, Vibert E, Campillo-Gimenez B, Edeline J. Long-Term Overall Survival After Selective Internal Radiation Therapy for Locally Advanced Hepatocellular Carcinomas: Updated Analysis of DOSISPHERE-01 Trial. J Nucl Med. 2024 Feb 1;65(2):264-269. doi: 10.2967/jnumed.123.266211.

Reference Type: DERIVED

PMID: 38212068 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33166497 (View on PubMed)

Other Identifiers

DOSISPHERES-01

Identifier Type: -

Identifier Source: org_study_id