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

Adenoma, Liver Cell Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02582034
• Other study ID #: DOSISPHERES-01
• Status: Completed
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: December 2018

Study information

• Verified date: January 2019
• Source: Center Eugene Marquis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 2018
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Adenoma
• Adenoma, Liver Cell
• Carcinoma, Hepatocellular

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	CHU Henri Mondor	Créteil
France	CHU Saint Eloi	Montpellier
France	Centre Eugène Marquis	Rennes
France	Gustave Roussy	Villejuif

Sponsors (1)

Lead Sponsor	Collaborator
Center Eugene Marquis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival		Up to 12 months
Secondary	Overall survival		Up to 30 months after inclusion of the 1st patient
Secondary	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
Secondary	Progression free survival not accessible to SIRT		Up to 12 months after treatment administration
Secondary	Post-therapeutic dosimetry measured by Positron emission tomography-computed tomography PET / CT	Dose delivered to the treated liver, the tumors, healthy liver and lings	Day one of treatment administration