Affordable Made-in-India Microspheres for Liver Cancer Therapy

NCT07436988 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: PGI/IEC/2025/EIC0013482025-26-247480
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Hepatecellular Carcinoma

Keywords

SIRT; Hepatocellular Carcinoma; 188Re-Microspheres; 90Y-Theraspheres; RADIANT; Targeted therapy; Liver Cancer; TARE

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (14)

• Change From Baseline in Blood Pressure

  Five time-points: Baseline and Week 2, 4, 8, 12 post-SIRT

• Change From Baseline in Body Temperature

  Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT

• Change From Baseline in Heart Rate

  Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT

• Incidence of Clinically Significant ECG Rhythm Abnormalities

  Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT

• Change From Baseline in ECG Interval Parameters

  Five time-points: Baseline and Weeks 2, 4, 8, 12 post-SIRT

Study Arms (2)

188Re-SIRT

EXPERIMENTAL

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

90Y-SIRT

ACTIVE COMPARATOR

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

Interventions

90Y-Theraspheres DEVICE

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.

Also known as: 90Y-Glass microspheres

90Y-SIRT

188Re-Microspheres DEVICE

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.

Also known as: 188Re-Metal microspheres

188Re-SIRT

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Portal vein thrombosis may be present or absent
• Laboratory criteria:
• Serum creatinine less than or equal to 1.5 mg per dL
• Total bilirubin less than or equal to 2.0 mg per dL
• AST or ALT less than or equal to 5 times upper limit of normal
• Leukocyte count greater than or equal to 1500 per microliter
• Platelet count greater than or equal to 50000 per microliter
• Prothrombin time less than or equal to 1.3 times control or INR less than or equal to 1.5
• Karnofsky performance status greater than 70
• Ability and willingness to provide written informed consent for participation in the IEC approved protocol

You may not qualify if:

• 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
• Myocardial infarction within the past six months
• Unstable arrhythmia or symptomatic cardiac disease
• Any other serious uncontrolled illness that in the investigator's opinion would compromise study participation
• History of other malignancy except adequately treated basal cell carcinoma or cervical carcinoma in situ within the last five years
• Major surgery within four weeks prior to enrolment
• Active uncontrolled bacterial infection requiring systemic therapy
• Liver rupture, tumor penetration of the liver capsule, tumor invasion of the biliary system, or biliary obstruction
• Known allergy or hypersensitivity to any component of the investigational or comparator microspheres
• Prior treatment with Selective Internal Radiation Therapy (SIRT)
• Estimated overall survival less than one month

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead
• Indian Council of Medical Research: collaborator

Study Sites (5)

Postgraduate Institute of Medical Education and Research

Chandigarh, Chandigarh, 160012, India

Location

Tata Memorial Hospital

Mumbai, Maharashtra, 400012, India

Location

All India Institute of Medical Sciences

Bhubaneswar, Odisha, 751019, India

Location

Jawaharlal Institute of Postgraduate Medical Education and Research

Puducherry, Puducherry, 605006, India

Location

All India Institute of Medical Sciences

Delhi, South Delhi, 110029, India

Location

Related Publications (5)

• 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.

  PMID: 30418210 BACKGROUND

• 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.

  PMID: 38241504 BACKGROUND

• 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.

  PMID: 36183659 BACKGROUND

• 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.

  PMID: 32516242 BACKGROUND

• 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.

  PMID: 38377367 BACKGROUND

Related 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

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Liver Neoplasms

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Jaya Shukla, Ph.D. Nuclear Medicine

  Post Graduate Institute of Medical Education and Research, Chandigarh

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prof. Jaya Shukla, Ph.D. Nuclear Medicine

CONTACT

+91-9781533400; shuklajaya@gmail.com

Prof. Naveen Kalra, MD Radiodiagnosis

CONTACT

+91 9855426320; navkal2004@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The study will be an open-label, randomized, dose-escalation Phase I study employing a 3+3 schema between the investigational product, 188Re-labeled GMP-grade freeze-dried microspheres. Commercially available 90Y-TheraSpheres will an intervention-type drug and will be used as the active comparator. A total of 18 patients: 12 in the 188Re intervention arm and 6 in the 90Y comparator arm (2:1) across the three dose cohorts. This sample size is typical for Phase I dose-escalation studies designed to determine a safe and feasible dose level for subsequent Phase II efficacy evaluation. After completion at each dose level, the Data Safety and Monitoring Committee will review the data within a week and opine about the decision to move to the next dose level.

Study Record Dates

• First Submitted: January 19, 2026
• First Posted: February 27, 2026
• Study Start: February 15, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): October 15, 2028
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

IN (5)