Hepatocellular Carcinoma Clinical Trial
— RETOUCHOfficial title:
RadioEmbolizaTion Using hOlmium-166 in Patients With Unresectable Hepatocellular Carcinoma: Prospective, Open Label, Single-center Pilot Study
Verified date | October 2022 |
Source | Erasme University Hospital |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Background: Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers and represents a growing health problem worldwide. Most patients present locally advanced disease and are candidates for palliative transarterial locoregional treatment. Transarterial radioembolization (TARE) using 90Y has been used for more than a decade for patients with advanced disease. The use of 166Ho could offer a more personalized approach in terms of imaging and dosimetry. Aim: to evaluate the feasibility and safety of TARE using 166Ho in a selected population of HCC patients and assess the biological peripheral response to this therapy. Materials and methods: In this open-label, prospective, non-randomized, singlecenter pilot study, 20 patients with unresectable hepatocellular carcinoma will undergo TARE using 166Ho. The primary outcome is the feasibility of 166Ho radioembolization as well as the assessment of safety and toxicity profiles (CTAE V5.0). Secondary outcomes include the evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular carcinoma, according to mRECIST and metabolic criteria, as well as the impact on the tumor marker alpha-fetoprotein (AFP), assessment of biodistribution/dosimetry using a "scout dose" and time to progression (TTP). A substudy will assess the hepatic function using 99mTc-IDA hepato-biliary scintigraphy (HBS) and the comparison between "pre-scout" HBS and HBS just after "scout dose". Finally, blood samples will be collected at different time points in order to explore the biological peripheral response to these therapies. Perspectives: The newly developed 166Ho-microspheres have distinctive advantages over the existing 90Ymicrospheres with improved dosimetry that represents a prerequisite for optimal safety and efficacy.
Status | Completed |
Enrollment | 20 |
Est. completion date | December 10, 2022 |
Est. primary completion date | June 10, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: - Patients must have given written informed consent - Adults = 18 years-old - Typical imaging or biopsy proven HCC according to EASL-EORTC guidelines (1) - Unresectable disease, BCLC B, or contraindicated for ablation, resection or transplantation, BCLC A, or BCLC C patients with no extra-hepatic extension, patients on the waiting list for resection or transplantation. - At least one measurable lesion on multiphasic CT or MRI - Preserved liver function with Child- Pugh score= B7 - ECOG performance status = 1 (Table 2) - Life expectancy =3 months - Efficient contraception for women - Platelets = 50000/m3 and PT= 50% - Hemoglobin =8.5 g/dl - Bilirubin = 2 mg/dl - ASAT/ALAT levels = 5x upper normal limit - Creatinine = 1.5x upper normal limit Exclusion Criteria: - Before work-up: - History of progressive, uncontrolled cancer other than HCC presenting liver metastasis. - >50% of liver involvement - Portal vein thrombosis of the main branch diagnosed on contrast enhanced images. Involvement of the right or left portal main branches and more distal is accepted - Evidence of extrahepatic disease - Unmanageable intolerance to contrast medium - Contraindication to hepatic angiography - Digestive hemorrhage due to portal hypertension in the 30 days preceding treatment - Previous systemic treatment, radiation therapy, transarterial loco-regional therapy or ablation therapy for HCC - Active infection or untreated active hepatitis (if detectable viral HBV load, treatment with a nucleoside analog should be instituted). - Pregnancy or breast feeding - Ascitis - Transjugular intrahepatic portosystemic shunt (TIPS) or portacaval shunt - Major surgery withing 4 weeks or incompletely healed surgical incision before starting study therapy - Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or severe depression. - Patients who are declared incapacitated - After work-up: - Lung absorbed dose > 30 Gy, as calculated using the 166Ho scout dose or 99mTc MAA - Uncorrectable extrahepatic deposition of the scout dose activity. Activity in the falciform ligament, portal lymph nodes and gallbladder is accepted. |
Country | Name | City | State |
---|---|---|---|
Belgium | Hôpital Universitaire Erasme, ULB | Brussels | Anderlecht |
Lead Sponsor | Collaborator |
---|---|
Erasme University Hospital | Terumo Europe N.V. |
Belgium,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Other | Assess the peripheral response to TA-LRT (i.e.: serum levels of tumor necrosis factor (TNF-alfa), interleukine-6 and 8 (IL6, IL8) and vascular endothelial growth factor (VEGF) at different time points of the study) | Baseline, day 1, day 14 and one month | ||
Other | Evaluation of hepatic function using 99mTc-IDA hepato-biliary scintigraphy (HBS) | 3 months | ||
Other | Comparison between "pre-scout" HBS and HBS just after "scout dose" | Baseline and immediately after the intervention | ||
Primary | Achievement of the selective radioembolization with Holmium-166 treatment in patients with HCC | Feasibility will be measured by the number of completed treatments and the percentage of injected activity compared to simulation | immediately after the SIRT session | |
Primary | Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 | % of patients with change in clinical, biological and radiological parameters | Day 1 | |
Primary | Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 | % of patients with change in clinical, biological and radiological parameters | 1 month | |
Primary | Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 | % of patients with change in clinical, biological and radiological parameters | 3 months | |
Primary | Incidence of Treatment-Emergent Adverse Events as assessed by CTCAE v5.0 | % of patients with change in clinical, biological and radiological parameters | 6 months | |
Secondary | Evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular carcinoma, according to mRECIST | mRECIST for HCC lesions: Evaluation of target lesions Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the target lesions Progressive Disease (PD): At least a 20% increase in the sum of the target lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD Evaluation of non-target lesions Complete Response (CR): Disappearance of all non-target lesions and normalization of tumor marker level Incomplete Response/ Stable Disease (SD): Persistence of one or more non-target lesion(s) or/and maintenance of tumor marker level above the normal limits Progressive Disease (PD): Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions |
3 months | |
Secondary | Evaluation of biodistribution/dosimetry using a scout dose | Tumoral and non-tumoral dose distribution in the liver and dose distribution in the lungs. | Day 5 | |
Secondary | Evaluation of tumor response marker alpha-fetoprotein | Baseline,1,3,6 Months | ||
Secondary | Time to progression (TTP) | Time elapsed from enrolment until objective tumor progression; does not include deaths | 6 months | |
Secondary | Microsphere concentration derived from 1.5T MRI R2* relaxivity measurements | Baseline and immediately after the intervention | ||
Secondary | Evaluation of efficacy of 166Ho radioembolization in unresectable hepatocellular using metabolic assessments (FDG and choline PET/CT) | % of patients that showed a complete metabolic response (CMR), partial metabolic response (PMR), no metabolic response (SMR), or progressive disease with new lesions. | 3 months |
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