Health Condition 1: C220- Liver cell carcinoma
Conditions
Interventions
Intervention1: 188Re-Microspheres: 1. Type of Intervention:
This intervention involves a radiopharmaceutical formulation 188Re-Microspheres designed for Selective Internal Radiation Therapy of unresec
Sponsors
Indian Council of Medical Research
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age greater than or equal to 18 years (male or female) 2. Histologically or radiologically confirmed diagnosis of HCC deemed inoperable 3. Barcelona Clinic Liver Cancer stage B with ECOG performance status between 0 and 2 4. At least one measurable lesion with longest diameter greater than or equal to 5 cm on cross sectional imaging 5. Portal vein thrombosis may be present or absent 6. Laboratory criteria: a. Serum creatinine less than or equal to 1.5 mg per dL b. Total bilirubin less than or equal to 2.0 mg per dL c. AST or ALT less than or equal to 5 times upper limit of normal d. Leukocyte count greater than or equal to 1500 per microliter e. Platelet count greater than or equal to 50000 per microliter f. Prothrombin time less than or equal to 1.3 times control or INR less than or equal to 1.5 7. Karnofsky performance status greater than 70 8. Ability and willingness to provide written informed consent for participation in the IEC approved protocol
Exclusion criteria
Exclusion criteria: 1. Women of childbearing potential who are unwilling or unable to use effective contraception or who are pregnant or lactating 2. Child Pugh class C liver function 3. Presence of extrahepatic metastases 4. Severe chronic pulmonary disease with hypoxemia or NYHA class three or four heart failure 5. Myocardial infarction within the past six months 6. Unstable arrhythmia or symptomatic cardiac disease 7. Any other serious uncontrolled illness that in the investigator s opinion would compromise study participation 8. History of other malignancy except adequately treated basal cell carcinoma or cervical carcinoma in situ within the last five years 9. Major surgery within four weeks prior to enrolment 10. Active uncontrolled bacterial infection requiring systemic therapy 11. Liver rupture, tumor penetration of the liver capsule, tumor invasion of the biliary system, or biliary obstruction 12. Known allergy or hypersensitivity to any component of the investigational or comparator microspheres 13. Prior treatment with Selective Internal Radiation Therapy (SIRT) 14. Estimated overall survival less than one month
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 188Re-Microspheres as unique, globally available 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.Timepoint: Day 1-Day 28 post-SIRT | — |
Secondary
| Measure | Time frame |
|---|---|
| Assessment of physiological safety will include monitoring changes in vital signs from baseline, focused physical examinations, 12 lead ECG findings, and ECOG performance status.Timepoint: Four time-points: Week 2, 4, 8 and 12 post-SIRT;Clinical laboratory safety will be assessed by monitoring changes from baseline in hematology (complete blood count), liver function tests including bilirubin, ALP, AST, and ALT, kidney function tests including serum creatinine and urea, and coagulation parameters including PT and INR evaluation.Timepoint: Four time-points: Week 2, 4, 8 and 12 post-SIRT;Quality of life assessment will be done by evaluating changes in Global Health Status on the EORTC QLQ-C30 (0-100) and in disease-specific symptom burden using the EORTC QLQ-HCC18 or WHOQOL-BREF if required locally, with analysis conducted as mean change and responder rates defined as a clinically meaningful change of 10 points or more.Timepoint: Three time-points: Baseline, 1 Month and 3-Months post-SIRT;Post-therapy biodistribution and dosimetry will be assessed using quantitative SPECT-CT to determine lung shunt fraction, tumor-to-normal liver ratio, and absorbed dose metrics including mean tumor dose, D70, mean normal liver dose, and mean lung dose, calculated using MIRD or voxel-based dosimetry methodsTimepoint: Multi time-point: 4 hrs, Day 1, 3, 5 and 7 post-SIRT;Systemic exposure to radioactivity will be evaluated by measuring blood and urine time activity at various intervals post-infusion in order to characterize systemic kinetics and estimate bone marrow radiation dose.Timepoint: Five time-points: Hour 0, 2, 12, 24, and 48;Preliminary antitumor activity will be assessed by determining the Objective Response Rate and Disease Control Rate using mRECIST criteria, along with changes in alpha-fetoprotein levelsTimepoint: 1. Objective Response Rate and Disease Control Rate: At Week 8 post-SIRT 2. Monitoring alpha-fetoprotein levels at three time-points: Baseline, Week 8 and Week | — |
Countries
India
Contacts
Public ContactDr Jaya Shukla
Postgraduate Institute of Medical Education and Research
Outcome results
None listed