Clinical trial NCT02582034: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adenoma, Liver Cell
Keywords: Optimized Dosimetry versus standard Dosimetry
Internal Radiation Therapy
Lead sponsor: Center Eugene Marquis
Sponsor class: OTHER
First posted: 2015-10-21
Enrollment: 56
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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
timeFrame: 3 months after treatment administration
Secondary outcomes:
measure: Progression Free Survival
timeFrame: Up to 12 months
measure: Overall survival
timeFrame: Up to 30 months after inclusion of the 1st patient
measure: 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).
timeFrame: Up to 12 months
measure: Progression free survival not accessible to SIRT
timeFrame: Up to 12 months after treatment administration
measure: Post-therapeutic dosimetry measured by Positron emission tomography-computed tomography PET / CT
timeFrame: Day one of treatment administration
Other outcomes:
Locations:
city: Créteil
country: France
facility: CHU Henri Mondor
city: Montpellier
country: France
facility: CHU Saint Eloi
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Villejuif
country: France
facility: Gustave Roussy
Study officials:
affiliation: Centre Eugène Marquis
name: Etienne GARIN, Pr
role: STUDY_CHAIR
References:
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.