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

NCT02582034 | Completed Phase 2

• 1 other identifier: DOSISPHERES-01
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 4

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.

Conditions

Adenoma, Liver Cell

Keywords

Optimized Dosimetry versus standard Dosimetry; Internal Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• 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

  3 months after treatment administration

Secondary Outcomes (5)

• Progression Free Survival

  Up to 12 months

• Overall survival

  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).

  Up to 12 months

• Progression free survival not accessible to SIRT

  Up to 12 months after treatment administration

• Post-therapeutic dosimetry measured by Positron emission tomography-computed tomography PET / CT

  Day one of treatment administration

Study Arms (2)

Standard dosimetry

ACTIVE COMPARATOR

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

Radiation: Standard Internal Radiation Therapy

Optimized dosimetry

EXPERIMENTAL

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

Interventions

Optimized Internal Radiation Therapy 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.

Optimized dosimetry

Standard Internal Radiation Therapy 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.

Standard dosimetry

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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,

You may not qualify if:

• 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

Sponsors & Collaborators

• Center Eugene Marquis: lead

Study Sites (4)

CHU Henri Mondor

Créteil, 94000, France

Location

CHU Saint Eloi

Montpellier, 34925, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

Gustave Roussy

Villejuif, France

Location

Related Publications (2)

• 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.

  PMID: 38212068 DERIVED

• 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.

  PMID: 33166497 DERIVED

MeSH Terms

Conditions

Adenoma, Liver Cell

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Etienne GARIN, Pr

  Centre Eugène Marquis

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 9, 2015
• First Posted: October 21, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: January 31, 2019

Record last verified: 2019-01

Locations

FR (4)