Affordable Made-in-India Microspheres for Liver Cancer Therapy (ReLIVE)

Multicentric Study on Indigenous and Affordable Microspheres for Selective Internal Radiation Therapy (SIRT) of Unresectable Liver Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatecellular Carcinoma
• Intervention / Treatment: Device: 188Re-Microspheres; Device: 90Y-Theraspheres

Detailed Description

Study Objective: Phase-1 Dose-escalation of 188Re-microspheres with comparator arm (Safety and primary efficacy)

Study Design: This is an open-label, multi-centric, randomized, dose escalation Phase I study with an active comparator arm (90Y-Theraspheres). The study will be initiated at PGIMER, Chandigarh, India and the other participating centres (AIIMS, New Delhi, India and TMH, Mumbai, India) would be added in a phased manner.

Study Settings:

The study will be conducted in the Department of Nuclear Medicine, PGIMER Chandigarh, which will serve as the coordinating and primary executing department, in collaboration with the Departments of Hepatology, Gastroenterology, and Phase I Centre of Clinical Pharmacology Unit, PGIMER Chandigarh, for patient screening, eligibility confirmation, therapeutic drug and dosimetry-related expertise, and overall conduct of Selective Internal Radiation Therapy (SIRT) in patients with hepatocellular carcinoma (HCC).

Study Design:

The study employs a 3+3 dose-escalation design in the investigational (188Re) arm, with parallel randomization to an active comparator (90Y) within each cohort in a 2:1 ratio. Three sequential tumor absorbed-dose cohorts are planned (80-100 Gy, 100-150 Gy, and 150-200 Gy). Dose escalation decisions will be based on the occurrence of dose-limiting toxicities (DLTs) during the predefined 28-day evaluation window and adjudicated by an independent Safety Review Committee (SRC). The total planned sample size is 18 patients (12 in the 188Re arm and 6 in the 90Y arm).

Study Protocol:

All patients will undergo a detailed pre-therapy assessment by the multidisciplinary study team prior to the procedure. This assessment will include a complete medical history, physical examination, review of performance status and laboratory investigations. Patients will be counseled regarding the procedure, expected benefits, and potential risks, and written informed consent will be obtained before any study-specific interventions.

Pre-therapy dosimetry will be performed to determine treatment feasibility and calculate the activity to be administered. In the 188Re arm, a lung shunt study using 99mTc-labelled microspheres will be performed on the day of therapy; in the 90Y arm, a 99mTc-MAA scan will be conducted at least one week prior to therapy so that desired dose may be imported. In both cases, a microcatheter will be placed via femoral artery puncture under digital subtraction angiography (DSA) guidance into the intended hepatic arterial branch. A scout dose of 3-5 mCi (111-185 MBq) of radiolabelled microspheres will be infused. Whole-body planar images will be acquired using a gamma camera equipped with an appropriate collimator, followed by regional SPECT/CT including the liver and tumor. Patient-specific attenuation correction will be performed using attenuation maps derived from the patients CT component. Image interpretation will be performed independently by two nuclear medicine physicians. Regions of interest (ROI) will be drawn on the liver, tumor, and lungs in anterior and posterior projections to calculate geometric mean counts. Lung shunt fraction (LSF) will be computed.

The tumor-to-normal liver ratio (TNR) will be calculated by placing an ROI over the area of maximal tumor uptake and a size-matched ROI over normal liver parenchyma; the count ratio will be recorded as TNR. Based on the CT tumor volume (cc) provided by the interventional radiologist, perfused liver mass (kg) will be obtained by multiplication with the liver tissue density (1.03 g/cc). The therapeutic activity to be administered will be calculated.

The calibration factor is 50 for 90Y and 34 for 188Re. The cohort-specified tumor dose will be delivered while ensuring that the mean absorbed dose to lungs and normal liver does not exceed 30 Gy, and the bone marrow dose does not exceed 2 Gy.

Before the treatment, the microcatheter position will be reconfirmed under DSA, and the calculated activity of 188Re microspheres (or standard-of-care 90Y microspheres) will be slowly infused. Intra-procedural DSA images will be acquired to confirm stasis or near-stasis of flow. The catheter will be flushed with saline after infusion. Residual activity in the vial and delivery set will be measured to determine the net administered dose. Radiation exposure at the hepatic region, injection site, and at one meter will be recorded. Post-SIRT tumor dose will be estimated using the monocompartmental method.

Post-therapy, serial whole-body images will be obtained during the patient's hospital stay, and a SPECT/CT scan will be performed at 24-48 hours to document microsphere biodistribution. Additional imaging may be obtained in selected patients to refine dosimetry, depending on logistical feasibility and radionuclide half-life. Personalized post-therapy dosimetry will be performed by drawing ROIs over the liver, tumor, lungs, and spleen on processed SPECT/CT images and applying the MIRD formula within dosimetry software to compute absorbed doses to each organ and the tumor. During hospitalization, laboratory tests (CBC, LFT, RFT) will be repeated, and any adverse events will be documented. Patients will be discharged after the 48-hour imaging, if clinically stable.

Study Endpoints:

Primary Endpoint:

Dose-Limiting Toxicity (DLT) rate (Day 1-Day 28): Proportion of patients experiencing ≥1 treatment-related DLT within 28 days post-SIRT, adjudicated per CTCAE v5.0 by the Safety Review Committee (SRC).

Pre-specified Dose-Limiting Toxicities (DLTs):

DLTs are defined as any of the following treatment-related toxicities occurring within Day 1 to Day 28 post-SIRT, meeting CTCAE v5.0 grade thresholds and judged by the Safety Review Committee (SRC) to be attributable to the investigational product or comparator.

i. Hepatic Toxicities: Radiation-Induced Liver Disease (RILD): Development of jaundice and/or ascites with a disproportionate rise in alkaline phosphatase, in the absence of tumor progression, biliary obstruction, or viral hepatitis flare.

ii. Radiation hepatitis: Defined as an elevation in AST, ALT, ALP or bilirubin in association with clinical features of hepatitis, attributable to SIRT. Radiation hepatitis will be considered when toxicity is Grade III or higher.

iii. Gastrointestinal Toxicities: Gastroduodenal ulcer or gastrointestinal bleeding: Confirmed by endoscopy or imaging, grade ≥ 3 severity, attributable to non-target deposition of microspheres.

iv. Biliary toxicity: Grade ≥ 3 events such as biliary stricture, cholangitis, or bile duct injury.

v. Pulmonary Toxicity:

1. Radiation pneumonitis: Clinical and radiological evidence of pneumonitis with CTCAE v5.0 grade ≥ 3, attributable to microsphere shunting to the lungs.

   Constitutional / Post-embolization Syndrome:

2. Post-radioembolization syndrome meeting grade ' ≥ 3 for any of the following:

Nausea/vomiting Abdominal pain Fatigue Loss of appetite or weight loss (>10% from baseline)

Other Serious Toxicities:

vi. Any other treatment-related grade ≥ 3 non-haematological toxicity considered clinically significant by the SRC.

vii. Grade ≥ 4 haematological toxicity persisting >7 days, attributable to study treatment.

DLT Characterization Parameters:

For each DLT, the following details must be systematically documented in the case report form (CRF) and reviewed by the SRC:

1. Type of toxicity: precise medical term per CTCAE v5.0
2. Grade: maximum severity reached
3. Time-to-onset: Interval from end of microsphere infusion to first documentation of toxicity
4. Duration: number of days from onset to resolution or stabilization
5. Action taken: treatment modification, hospitalization, dose interruption, or supportive care measures
6. Outcome: recovered/resolved, ongoing, recovered with sequelae, death, or unknown

Treatment-Emergent Adverse Events (TEAEs/SAEs):

Incidence, nature, and severity of TEAEs/SAEs from end-of-procedure through 12 weeks (timepoints: end-of-procedure, 12 h, 24 h, Day 7, Day 14, Weeks 4, 8, 12), graded by CTCAE v5.0, causality by WHO-UMC. All SAE will be reported and compensated as per NDCT 2019, through insurance bought for the purpose.

Serious Adverse Event:

Serious adverse events (SAEs) are those that result in death, are life-threatening, require hospitalization or prolong an existing hospital stay, lead to significant disability, cause congenital anomalies, or necessitate urgent intervention to prevent permanent harm. SAEs will be recorded and reported in accordance with the Third Schedule of the New Drugs and Clinical Trials Rules, 2019.

SAE Reporting Timeline:

1. Initial IEC/IRB notification: Any SAE will be reported to the Institute Ethics Committee (IEC) within 24 hours of its occurrence with a covering letter from the Principal Investigator (PI).
2. Follow-up IEC/IRB report: A detailed follow-up SAE report will be submitted within 14 calendar days of occurrence.
3. Format and mode: The SAE report package will be sent as both hard copy and soft copy (MS Word format) to the IEC office.
4. IEC will send its opinion/recommendation (including causality and compensation, if applicable) to CDSCO/DCGI, with copy to the Sponsor, within 30 days of IEC receipt of the SAE dossier.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Prof. Jaya Shukla, Ph.D. Nuclear Medicine; Phone Number: +91-9781533400; Email: shuklajaya@gmail.com
• Study Contact Backup: Name: Prof. Naveen Kalra, MD Radiodiagnosis; Phone Number: +91 9855426320; Email: navkal2004@yahoo.com

Study Locations

• India
  • Chandigarh
    • Chandigarh, Chandigarh, India, 160012
      • Postgraduate Institute of Medical Education and Research
      • Contact: Prof. Jaya Shukla, Ph.D. Nuclear Medicine; Phone Number: +91-9781533400; Email: shuklajaya@gmail.com
      • Contact: Prof. Naveen Kalra, MD Radiodiagnosis; Phone Number: +91 9855426320; Email: navkal2004@yahoo.com
      • Principal Investigator: Prof Jaya Shukla, Ph.D. Nuclear Medicine
      • Sub-Investigator: Prof. Ajay Duseja, DM Hepatology
      • Sub-Investigator: Prof. Naveen Kalra, MD Radiodiagnosis
      • Sub-Investigator: Prof. Nusrat Shafiq, DM Clinical Pharmacology
      • Sub-Investigator: Dr. Rajender Kumar, MD Nuclear Medicine
      • Sub-Investigator: Dr. Harmandeep Singh, MD Nuclear Medicine
      • Sub-Investigator: Dr. Harish Bhujade, MD Radiodiagnosis
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • Tata Memorial Hospital
      • Contact: Prof. Venkatesh Rangarajan, DRM Nuclear Medicine; Phone Number: +91-9969014183; Email: drvrangarajan@gmail.com
      • Contact: Prof. Ameya Puranik, DNB Nuclear medicine; Phone Number: +91-9619811125; Email: ameya2812@gmail.com
      • Sub-Investigator: Prof. Venkatesh Rangarajan, MD Nuclear Medicine
      • Sub-Investigator: Prof. Ameya Puranik, DNB Nuclear Medicine
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • All India Institute of Medical Sciences
      • Contact: Dr. Kanhaiyalal Agrawal, MD Nuclear Medicine; Phone Number: +91-8195930013; Email: drkanis@gmail.com
      • Contact: Dr. Tara Prasad Tripathy, MD Radiodiagnosis; Phone Number: +91-8575827990; Email: radiol_tara@aiimsbhubaneswar.edu.in
      • Principal Investigator: Dr. Kanhaiyalal Agrawal, MD Nuclear Medicine
      • Sub-Investigator: Dr. Tara Prasad Tripathy, MD Radiodiagnosis
      • Sub-Investigator: Dr. Manas Kumar Panigrahi, DM Gastroenterology
  • Puducherry
    • Puducherry, Puducherry, India, 605006
      • Jawaharlal Institute of Postgraduate Medical Education and Research
      • Contact: Prof. Dhanapathi H Halanaik, MD Nuclear Medicine; Phone Number: +91-9486398901; Email: dhanapathih@gmail.com9486398901
      • Contact: Dr. Santha Kumar Senthilvelan, DM Interventional Radiology; Phone Number: +91-79442357488; Email: santhakumar9001@gmail.com
      • Sub-Investigator: Prof. Dhanapathi H Halanaik, MD Nuclear Medicine
      • Sub-Investigator: Prof. Nandini Pandit, DNB Nuclear Medicine
      • Sub-Investigator: Dr. Santha Kumar Senthilvelan, DM Interventional Radiology
  • South Delhi
    • Delhi, South Delhi, India, 110029
      • All India Institute of Medical Sciences
      • Contact: Prof. Shamim Ahmad Shamim, MD Nuclear Medicine; Phone Number: +91-9868350491; Email: sashamim2002@gmail.com
      • Contact: Prof. Shivanand Gamanagatti, MD Radiodiagnosis; Phone Number: +91-9868658057; Email: shiv223@gmail.com
      • Principal Investigator: Prof. Shamim Ahmed Shamim, MD Nuclear Medicine
      • Sub-Investigator: Prof. Shivanand Gamanagatti, MD Radiodiagnosis
      • Sub-Investigator: Prof. Maroof Ahmad Khan, Ph.D. Biostatistics
      • Sub-Investigator: Prof. Shalimar, DM Gastroenterology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

   1. Serum creatinine less than or equal to 1.5 mg per dL
   2. Total bilirubin less than or equal to 2.0 mg per dL
   3. AST or ALT less than or equal to 5 times upper limit of normal
   4. Leukocyte count greater than or equal to 1500 per microliter
   5. Platelet count greater than or equal to 50000 per microliter
   6. 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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 188Re-SIRT; The experimental arm will evaluate the safety, tolerability, biodistribution, and preliminary efficacy of indigenous 188Re-Microspheres for SIRT in unresectable HCC. Participants will be enrolled in three dosing cohorts (80-100 Gy, 100-150 Gy, 150-200 Gy) with 4 patients receiving 188Re-Microspheres per cohort. Pre-therapy assessments will include clinical evaluation, laboratory tests, serology, Child-Pugh score, AFP, portal vein status, and triple-phase CT/MRI/PET-CT. Lung shunt study using 99mTc-Microspheres will be performed on day of SIRT to calculate the 188Re-Microspheres activity required for intended dose. 188Re-Microspheres will be delivered via single femoral artery catheter under DSA, followed by post-therapy SPECT/CT for biodistribution and dosimetry. Patients will be monitored for laboratory parameters, adverse events, and tumor response up to 12 weeks using mRECIST. Dose escalation will proceed only if dose-limiting toxicity is not observed in more than 1 of 3 patients.	Device: 188Re-Microspheres; Indigenous 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.; Other Names: 188Re-Metal microspheres
Active Comparator: 90Y-SIRT; The comparator arm aims to compare the safety, tolerability, biodistribution, and preliminary efficacy of 188Re-Microspheres with the standard-of-care 90Y-Microspheres for SIRT in unresectable HCC. Tumor dose escalation will be conducted in a phased manner across three groups receiving 80-100, 100-150, and 150-200 Gy. Prior to therapy, patients will undergo clinical evaluation, laboratory investigations, serological testing, and imaging with triple phase CT/MRI/PET-CT. 99mTc-MAA will be administered via trans-arterial catheter placed by femoral artery puncture under DSA at least one week prior to SIRT for lung shunt estimation and determination of the therapeutic dose of 90Y-Theraspheres. On the day of SIRT, the patient will be catheterized again, and the calculated Y90-Theraspheres dose will be delivered under DSA. Post-therapy PET-CT will be performed to assess biodistribution. Dose escalation will proceed only if dose-limiting toxicity is not observed in more than 1 of 3 patients.	Device: 90Y-Theraspheres; Standard-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.; Other Names: 90Y-Glass microspheres

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Day 1 - Day 28 Post-SIRT

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Five time-points: Baseline and Week 2, 4, 8, 12 post-SIRT
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.	Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT
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.	Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT
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.	Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT
Change From Baseline in ECG Interval Parameters	Standard 12-lead ECG recordings will be obtained at each visit. Change from baseline will be calculated for the following interval parameters measured in milliseconds: PR interval, QRS duration, and corrected QT interval (QTc). Each parameter will be analyzed and reported separately within this outcome measure using descriptive statistics.	Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT
Change From Baseline in ECOG Performance Status Score	Functional status will be assessed using the Eastern Cooperative Oncology Group (ECOG) performance status scale (range 0-5). Changes from baseline ECOG score will be summarized at each post-treatment visit.	Baseline and Weeks 2, 4, 8, 12 post-SIRT
Number of Participants With Grade ≥3 Laboratory Abnormalities as Assessed by CTCAE v5.0	Laboratory safety will be assessed using CTCAE version 5.0. Haematology parameters (complete blood count), liver function tests (bilirubin, ALP, AST, ALT), renal function tests (serum creatinine, urea), and coagulation parameters (PT, INR) will be graded according to CTCAE criteria. The outcome will be summarised as the number and proportion of participants experiencing at least one Grade ≥3 laboratory abnormality during the post-SIRT follow-up period.	Five time-points: Baseline and Week 2, 4, 8, 12 post-SIRT
Systemic Exposure to Radioactivity	This 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.	Five time-points: Hour 0, 2, 12, 24, and 48
Quantitative Estimation of Post-therapy Biodistribution and Absorbed Dose Using SPECT/CT	Post-therapy biodistribution and dosimetry will be assessed using quantitative single-photon emission computed tomography-computed tomography (SPECT-CT). Dosimetric parameters will include lung shunt fraction, tumor-to-normal liver uptake ratio, mean absorbed tumor dose, mean absorbed normal liver dose, and mean absorbed lung dose, calculated using Medical Internal Radiation Dose (MIRD) based or voxel based dosimetry methods. These parameters will be aggregated into a single binary outcome per participant, defined as acceptable post-therapy dosimetry, meeting all of the following criteria: Tumor absorbed dose ≥ protocol-specified therapeutic threshold; Mean absorbed normal liver dose within predefined safety limits; Mean absorbed lung dose within predefined safety limits The outcome will be reported as the number and proportion of participants meeting acceptable dosimetry criteria.	Day 0, Day 1, Day 2
Evaluation of Preliminary Therapeutic Efficacy of 188Re-SIRT via Radiologic Response	Preliminary antitumor activity will be evaluated based on radiologic tumor response using modified Response Evaluation Criteria in Solid Tumors (mRECIST). Participants will be categorized as having complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Outcomes will be summarized separately as Objective Response Rate (proportion of participants achieving CR or PR) and Disease Control Rate (proportion achieving CR, PR, or SD).	Single time-point: Week 8 post-SIRT
Evaluation of Preliminary Therapeutic Efficacy of 188Re-SIRT via Biochemical Response	Biochemical response will be assessed by change from baseline in serum alpha-fetoprotein (AFP) levels, measured in nanograms per millilitre (ng/mL)	Three time-points: Baseline, Week 8 and Week 12 post-SIRT
Change From Baseline in Quality of Life Scores as Measured by the World Health Organization Quality of Life-BREF (WHOQOL-BREF)	Quality of life will be assessed using the WHOQOL-BREF questionnaire, which evaluates physical, psychological, social, and environmental domains. Domain scores range from 0 to 100, with higher scores indicating better quality of life. Outcomes will be summarized as mean change from baseline and responder rates defined as a clinically meaningful change of ≥10 points	Baseline, 1 month, and 3 months post-SIRT
Change From Baseline in Hepatocellular Carcinoma-Specific Symptom Scores as Measured by the EORTC QLQ-HCC18	Disease-specific symptom burden will be assessed using the EORTC QLQ-HCC18 questionnaire. Domain scores range from 0 to 100, with higher scores indicating greater symptom burden (worse symptoms). Outcomes will be summarized as mean change from baseline and the proportion of participants experiencing a clinically meaningful change, defined as a change of ≥10 points.	Baseline, 1 month, and 3 months post-SIRT
Proportion of Participants Meeting Composite Procedural Safety Criteria for SIRT	Procedural safety and technical performance of SIRT will be assessed using a composite procedural endpoint. For each participant, the procedure will be classified as successful and safe if all of the following criteria are met: Successful selective catheter delivery of Re-188 microspheres to the intended hepatic arterial territory; Absence of non-target microsphere deposition on post-therapy imaging; Radiation exposure as measured over the liver, at the injection site and at a distance of one meter following microsphere administration The outcome will be reported as the number and proportion of participants meeting all procedural safety criteria.	Single time-point: Immediately after performing SIRT

Collaborators and Investigators

• Sponsor: Post Graduate Institute of Medical Education and Research, Chandigarh
• Collaborators: Indian Council of Medical Research
• Investigators: Principal Investigator: Jaya Shukla, Ph.D. Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh

Publications and helpful links

General Publications

• Shukla J, Kalra N, Kumar R, Bhusari P, Chhabra A, Parmar M, Vatsa R, Singh H, Duseja A, Mittal BR. Two Cases of 188Re Microspheres for Inoperable Hepatocellular Carcinoma. Clin Nucl Med. 2019 Feb;44(2):e93-e95. doi: 10.1097/RLU.0000000000002373.
• Aggarwal A, Kaur G, Jassal RS, Medhi B, Mittal BR, Shukla J. Unraveling Interaction of Rhenium-188 Microspheres with Primary Hepatic Cancer Cell: A Breakthrough Study. Cancer Biother Radiopharm. 2024 Apr;39(3):188-195. doi: 10.1089/cbr.2023.0146. Epub 2024 Jan 19.
• Shukla J, Goyal A, Chhabra A, Rathore Y, Bansal K, Pandey S, Parmar M, Singhal S, Kalra N, Duseja A, Mittal BR. Cold kit for Rhenium-188 microspheres based selective intra-arterial therapy (SIRT): Preparation, characterization and feasibility study. Appl Radiat Isot. 2022 Dec;190:110423. doi: 10.1016/j.apradiso.2022.110423. Epub 2022 Aug 28.
• Shukla J, Kalra N, Mittal BR, Duseja A, Kumar R, Singh H, Chaluvashetty SB, Parmar M, Krishnan S, Kumar G, Vatsa R, Chhabra A, Bansal K, Rathore Y, Pandey S. Freeze-dried microspheres for selective intra-arterial radionuclide therapy: an affordable solution. Nucl Med Commun. 2020 Aug;41(8):817-823. doi: 10.1097/MNM.0000000000001225.
• Shukla J, Chopra S, Kaur K, Chakraborty S, Singh H, Duseja A, Kalra N, Mittal BR. 177 Lu-Microspheres Selective Intra-arterial Radionuclide Therapy : A Facile and Biocompatible Permanent Micro-Seed Implants for Unresectable Hepatocellular Carcinoma. Clin Nucl Med. 2024 Apr 1;49(4):e170-e171. doi: 10.1097/RLU.0000000000005101. Epub 2024 Feb 6.

Helpful Links

• The link shows the study protocol for the STOP-HCC Phase 3 Randomized Controlled Trial for 90Y-Glass microspheres SIRT in unresectable HCC
• his study evaluates the safety and effectiveness of SIRT using SIR-Spheres Y-90 resin microspheres as a first-line treatment for patients with liver-limited metastatic colorectal cancer.
• An open-label prospective trial of TheraSphere treatment for patients with liver metastases who have failed or are intolerant to other therapies
• This protocol describes a Phase 3 randomized trial assessing the efficacy and safety of TheraSphere Yttrium-90 glass microspheres combined with second-line chemotherapy in patients with metastatic colorectal cancer liver metastases

Study record dates

Study Major Dates

• Study Start (Estimated): February 15, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): October 15, 2028

Study Registration Dates

• First Submitted: January 19, 2026
• First Submitted That Met QC Criteria: February 20, 2026
• First Posted (Actual): February 27, 2026

Study Record Updates

• Last Update Posted (Actual): March 12, 2026
• Last Update Submitted That Met QC Criteria: March 11, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Targeted therapy; Liver Cancer; SIRT; TARE; RADIANT; 188Re-Microspheres; 90Y-Theraspheres
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Carcinoma, Hepatocellular; Liver Neoplasms
• Other Study ID Numbers: PGI/IEC/2025/EIC001348; 2025-26-247480 (Other Grant/Funding Number: Indian Council of Medical Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data may be shared on reasonable requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No