Primary liver tumors, with hepatocellular carcinoma (HCC) accounting for 80%, represent 6% of global cancer incidence and 9% of global cancer-associated mortality.HCC remains the leading causes of cancer-related deaths worldwide, due to late diagnosis. Although local-stage liver tumors are curable with tumor resection or livertransplantation, 65-70% of diagnosed cases are not suitable for resection due to large or multifocal lesions. For these patients, local therapies such as transcatheterarterial chemoembolization (TACE) or selective internal radiation therapy (SIRT) are appropriate at intermediate stages. In cases of advanced and metastatic livertumors, systemic therapies like sorafenib are the standard approach. Selective Intra-arterial Radionuclide Therapy (SIRT) offers a promising treatment for inoperableliver tumors by delivering beta-emitting radiolabeled microspheres directly to tumor sites through the liver's dual blood supply. However, the high cost of standard90Y-microspheres has limited accessibility for patients. This current project aims to develop, optimize, and validate the indigenously prepared microspheres forradiolabeling with 188Re from commercially available generator and indigenously produced radionuclide 177Lu (BARC Mumbai) for SIRT in liver cancer. With hightransformational impact, the current multicentric research will lead to a potentially safe, effective, and promising low-cost SIRT solution for low-income settings.Through collaboration across multiple centers, the study will evaluate the efficacy of microspheres labelled with both radionuclides. By establishing these accessibleSIRT options, this project strives to reduce financial barriers to treatment, advancing the goals of "Jai Anusandhan" towards building innovative therapeutics throughcollaborative research project and improving outcomes for patients with limited options.
Age greater than or equal to 18 years (male or female)
Histologically or radiologically confirmed diagnosis of HCC deemed inoperable
Barcelona Clinic Liver Cancer stage B with ECOG performance status between 0 and 2
At least one measurable lesion with longest diameter greater than or equal to 5 cm on cross sectional imaging
Women of childbearing potential who are unwilling or unable to use effective contraception or who are pregnant or lactating
Child Pugh class C liver function
Presence of extrahepatic metastases
Severe chronic pulmonary disease with hypoxemia or NYHA class three or four heart failure
Parallel
90Y-Theraspheres
DeviceStandard-of-care 90Y-Theraspheres will be delivered via femoral artery catheter under digital subtraction angiography (DSA) for intra-arterial SIRT. Pre-therapy angiographic mapping and 99mTc-MAA lung shunt study will be conducted at least one week before SIRT to delineate hepatic arterial anatomy, detect extrahepatic shunts, and determine lung shunt fraction for personalized dose calculation. On the day of therapy, the patient will undergo a second femoral artery catheterization, and the calculated 90Y-Theraspheres dose will be infused selectively into the hepatic artery supplying the tumor. Intra-procedural DSA imaging will monitor catheter position, stasis, and microsphere delivery. Post-therapy PET-CT will be performed to assess microsphere distribution. The absorbed doses to tumor, healthy liver and lungs will be estimated using partition method. Patients will be monitored for laboratory parameters, adverse events, and tumor response using mRECIST criteria up to 12 weeks.
188Re-Microspheres
DeviceIndigenous 188Re-Microspheres will be administered via femoral artery catheter under DSA for intra-arterial SIRT. Pre-therapy angiographic mapping and lung shunt assessment using 99mTc-Microspheres will be performed on the same day to delineate hepatic arterial anatomy, detect extrahepatic shunts, and determine lung shunt fraction for administered activity estimation. The 188Re-Microspheres will be selectively infused into the hepatic artery supplying the tumor, with intra-procedural DSA monitoring for catheter placement and stasis. Post-therapy SPECT/CT will be performed 24-48 hours after administration, allowing accurate confirmation of microsphere distribution and dosimetry, which is an advantage over standard 90Y-Theraspheres requiring separate pre- and post-procedure imaging. This single-session approach reduces procedural complexity and resource use. Patients will be monitored for laboratory parameters, adverse events, and tumor response using mRECIST criteria up to 12 weeks.
Number of Participants with Dose-Limiting Toxicity (DLT) as assessed by CTCAE v4.0
Microspheres cold-kit is unique, GMP-grade innovative formulation with enhanced shelf-life and affordability. The clinical validation of 188Re-Microspheres across a broad spectrum of patients nationwide (Pan India) will ensure market readiness. Once available, this cost-effective treatment has the potential to benefit a large number of patients with HCC who previously had limited access to such therapies. The primary endpoint will be assessment of Dose-Limiting Toxicity (DLT) from Day 1 to Day 28. Proportion of patients experiencing more than or equal to 1 treatment related DLT within 28 days post-SIRT, adjudicated per CTCAE v5.0 by the Safety Review Committee, will be noted.
Change From Baseline in Blood Pressure
Systolic and diastolic blood pressure (mmHg) will be measured at each visit. Change from baseline will be calculated separately for systolic and diastolic blood pressure as the difference between baseline and post-treatment values. Results will be summarized using descriptive statistics for each component.
Change From Baseline in Body Temperature
Body temperature (°C) will be measured at each visit. Change from baseline will be calculated as the difference between baseline and post-treatment body temperature values and summarized using descriptive statistics.
Change From Baseline in Heart Rate
Heart rate (Beats per minute) will be measured at each visit. Change from baseline will be calculated as the difference between post-treatment and baseline heart rate values and summarized using descriptive statistics.
Incidence of Clinically Significant ECG Rhythm Abnormalities
Incidence of new or worsening clinically significant ECG abnormalities, including arrhythmias or conduction disturbances, identified on 12-lead ECG will be noted.
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Post Graduate Institute of Medical Education and Research, Chandigarh
Lead sponsor
Indian Council of Medical Research
Collaborator
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