| CTRI Number |
CTRI/2025/11/097219 [Registered on: 11/11/2025] Trial Registered Prospectively |
| Last Modified On: |
04/02/2026 |
| Post Graduate Thesis |
No |
| Type of Trial |
Interventional |
|
Type of Study
|
Medical Device
Radiation Therapy |
| Study Design |
Randomized, Parallel Group, Multiple Arm Trial |
|
Public Title of Study
|
Affordable treatment for Liver Cancer |
|
Scientific Title of Study
|
Phase I Multicentric Dose-Escalation Study of Indigenous,
Affordable Microspheres for Selective Internal Radiation
Therapy (SIRT) in Patients with Unresectable Liver Cancer |
| Trial Acronym |
|
|
Secondary IDs if Any
|
| Secondary ID |
Identifier |
| NIL |
NIL |
|
|
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
|
| Name |
Dr Jaya Shukla |
| Designation |
Professor |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Sector-12
Chandigarh
CHANDIGARH
160012
India |
| Phone |
7087009134 |
| Fax |
|
| Email |
shuklajaya@gmail.com |
|
Details of Contact Person
Scientific Query
|
| Name |
Dr Jaya Shukla |
| Designation |
Professor |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Sector-12
Chandigarh
CHANDIGARH
160012
India |
| Phone |
7087009134 |
| Fax |
|
| Email |
shuklajaya@gmail.com |
|
Details of Contact Person
Public Query
|
| Name |
Dr Jaya Shukla |
| Designation |
Professor |
| Affiliation |
Postgraduate Institute of Medical Education and Research |
| Address |
Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Sector-12
Chandigarh
CHANDIGARH
160012
India |
| Phone |
7087009134 |
| Fax |
|
| Email |
shuklajaya@gmail.com |
|
|
Source of Monetary or Material Support
|
| Indian Council of Medical Research |
|
|
Primary Sponsor
|
| Name |
Indian Council of Medical Research |
| Address |
V. Ramalingaswami Bhawan, P.O. Box No. 4911, Ansari Nagar, New Delhi - 110029 |
| Type of Sponsor |
Government funding agency |
|
|
Details of Secondary Sponsor
|
|
|
Countries of Recruitment
|
India |
|
Sites of Study
|
| No of Sites = 5 |
| Name of Principal
Investigator |
Name of Site |
Site Address |
Phone/Fax/Email |
| Dr Kanhaiya Lal Agarwal |
All India Institute of Medical Sciences |
Department of Nuclear Medicine; Department of Radio Diagnosis and Imaging
Khordha
ORISSA |
8195930013
drkanis@gmail.com |
| Prof Shamim Ahmad Shamim |
All India Institute of Medical Sciences |
Department of Nuclear Medicine; Department of Radio Diagnosis and Imaging, Ansari Nagar
New Delhi
DELHI |
9868350491
sashamim2002@gmail.com |
| Prof Dhanpathi Halnaiik |
Jawaharlal Institute of Postgraduate Medical Education and Research |
Department of Nuclear Medicine; Department of Radio Diagnosis and Imaging
Pondicherry
PONDICHERRY |
9486398901
dhanapathih@gmail.com |
| Prof Jaya Shukla |
Postgraduate Institute of Medical Education and Research |
Department of Nuclear Medicine, Department of Radiodiagnosis
Chandigarh
CHANDIGARH |
9781533400
shuklajaya@gmail.com |
| Prof Venkatesh Rangarajan |
Tata Memorial Hospital |
Depaerment of Nuclear Medicine, Homi Babha Building, Dr Ernest Borges Rd, Parel East, Parel
Mumbai
MAHARASHTRA |
9969014183
drvrangarajan@gmail.com |
|
|
Details of Ethics Committee
|
| No of Ethics Committees= 1 |
| Name of Committee |
Approval Status |
| Institutional Ethics Committee, PGIMER Chandigarh |
Approved |
|
|
Regulatory Clearance Status from DCGI
|
|
|
Health Condition / Problems Studied
|
| Health Type |
Condition |
| Patients |
(1) ICD-10 Condition: C220||Liver cell carcinoma, |
|
|
Intervention / Comparator Agent
|
| Type |
Name |
Details |
| Intervention |
188Re-microspheres |
This study involves delivery of indigenous Rhenium-188 (188Re)-Microspheres designed for Selective Internal Radiation Therapy (SIRT) of unresectable liver cancer.
The purpose of Phase-I is to evaluate the safety, tolerability, biodistribution, and preliminary efficacy of 188Re-Microspheres in patients with unresectable HCC.
There will be three dose groups with 80-100 Gy, 100-150 Gy, and 150-200 Gy planned tumor absorbed dose. The activity to be administered will depend on the intended absorbed dose.
The patients will be assessed by the study team prior to the procedure. Pre-therapy assessment will include clinical history, laboratory tests complete blood counts (CBC), prothrombin time (PT), liver function test (LFT), renal function test (RFT), serology for hepatitis B or C infection and triple phase (TP) CT-MRI/PET-CT for treatment planning. The Child Pugh score, alpha fetoprotein (AFP) and portal vein status will also be documented. The informed written consent will be obtained from the patients.
The lung shunt study for dose calculation will be done with 99mTc-microspheres, for 188Re group, on the day of therapy and with 99mTc-MAA, at least one week before, for 90Y group (control group). A trans-arterial catheter will be placed by femoral artery puncture by intervention radiologist in digital subtraction angiography (DSA) room and a scout dose of 111-185 MBq 99mTc- Microspheres/MAA will be delivered. The gamma camera images will be acquired to calculate lung shunt and to calculate therapy dose of 188Re-Microspheres and keeping maximum absorbed dose to lung, normal liver and bone marrow below 30 Gy, 30 Gy and 2 Gy respectively. The patient will be shifted to DSA room and calculated therapy dose of 188Re/90Y-Microspheres will be delivered. The intra-procedural DSA images will be acquired. The catheter will be flushed with saline after infusion of radiolabelled microspheres. The activity in vial and syringe will be measured to calculate the administered dose. The radiation exposure above the liver, at the injection site and at one meter will be documented. Post-therapy serial whole body (WB) images will be acquired during the period of hospitalization. One SPECT-CT image will also be obtained up to 24 h and/or 48 hrs to observe the biodistribution and personalized dosimetry of delivered microspheres. During the hospitalization, patients laboratory tests (CBS, LFT, RFT) will be repeated and adverse event (if any) will be recorded.
The response to SIRT will be assessed on TPCT or PET-TPCT after 8-12 weeks post therapy based on modified response evaluation criteria in solid tumors (mRECIST). The next dosing cohort will be only initiated only after analysing 14 day follow up results of the first cohort of patients. Dose escalation will be carried out only if Dose Limiting Toxicity is not observed in more than 1 out of 3 patients in each of the intervention treatment arm in the first cohort. |
| Comparator Agent |
Y90-Theraspheres |
This study involves delivery of the current standard-of-care, Yttrium-90 (Y90)-Theraspheres, for Selective Internal Radiation Therapy (SIRT) of unresectable liver cancer. The purpose of Phase I is to evaluate the safety, tolerability, biodistribution, and preliminary efficacy of 188Re-Microspheres and to compare these outcomes with 90Y-Theraspheres. Three dose groups are planned including 80-100 Gy, 100-150 Gy, and 150-200 Gy, with administered activity based on intended absorbed dose. Patients will undergo pre-therapy assessment including clinical history, laboratory tests (CBC, PT, LFT, RFT), serology for hepatitis B and C, and triple-phase CT or MRI. Child Pugh score, AFP, and portal vein status will also be documented. Written informed consent will be obtained.
The lung shunt study for 90Y-Theraspheres will be done with 99mTc-MAA at least one week prior to therapy. A femoral artery catheter will be placed in the DSA room, and a scout dose of 111-185 MBq 99mTc-MAA will be delivered. Gamma camera imaging will determine lung shunt and therapy dose while keeping maximum absorbed dose to lung, liver, and bone marrow below 30 Gy, 30 Gy, and 2 Gy. On the day of SIRT, the patient will be catheterized again, and the calculated 90Y-Theraspheres dose will be delivered. Intra-procedural DSA images will be acquired, the catheter flushed with saline, and administered activity recorded. Radiation exposure at the liver, injection site, and at one meter will be documented.
Post-therapy regional PET-CT will be performed after 1-4 h to assess the biodistribution and dosimetry. Laboratory tests will be repeated and adverse events recorded. Response will be evaluated on TPCT or PET-TPCT at 8-12 weeks using mRECIST. The next cohort will be initiated only after analyzing 14-day follow-up results. Dose escalation will proceed only if dose-limiting toxicity is not observed in more than one of three patients in the Y90 arm. |
|
|
Inclusion Criteria
|
| Age From |
18.00 Year(s) |
| Age To |
90.00 Year(s) |
| Gender |
Both |
| Details |
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 |
|
| ExclusionCriteria |
| Details |
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 |
|
|
Method of Generating Random Sequence
|
Computer generated randomization |
|
Method of Concealment
|
Centralized |
|
Blinding/Masking
|
Open Label |
|
Primary Outcome
|
| Outcome |
TimePoints |
| 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. |
Day 1-Day 28 post-SIRT |
|
|
Secondary Outcome
|
| Outcome |
TimePoints |
| Assessment of physiological safety will include monitoring changes in vital signs from baseline, focused physical examinations, 12 lead ECG findings, and ECOG performance status. |
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. |
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. |
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 methods |
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. |
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 levels |
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 12 post-SIRT |
| Procedural and technical outcomes will be evaluated by assessing the technical success of selective catheter delivery, the presence or absence of non-target microsphere deposition on post-therapy imaging, and radiation safety field readings over the liver, at the injection site, and at one meter distance |
Single time-point: Immediately after performing SIRT |
|
|
Target Sample Size
|
Total Sample Size="150"
Sample Size from India="150"
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" |
|
Phase of Trial
|
Phase 1 |
|
Date of First Enrollment (India)
|
01/12/2025 |
| Date of Study Completion (India) |
Applicable only for Completed/Terminated trials |
| Date of First Enrollment (Global) |
Date Missing |
| Date of Study Completion (Global) |
Applicable only for Completed/Terminated trials |
|
Estimated Duration of Trial
|
Years="3"
Months="0"
Days="0" |
Recruitment Status of Trial (Global)
Modification(s)
|
Not Yet Recruiting |
| Recruitment Status of Trial (India) |
Open to Recruitment |
|
Publication Details
|
N/A |
|
Individual Participant Data (IPD) Sharing Statement
|
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
|
|
Brief Summary
|
Primary liver tumors, with hepatocellular carcinoma accounting for eighty percent of cases, represent six percent of global cancer incidence and nine percent of cancer-related mortality. Hepatocellular carcinoma remains a leading cause of cancer-related deaths worldwide due to late diagnosis. While local-stage liver tumors can be treated with tumor resection or liver transplantation, sixty-five to seventy percent of diagnosed cases are not suitable for resection because of large or multifocal lesions. For these patients, local therapies such as transcatheter arterial chemoembolization or selective internal radiation therapy are appropriate at intermediate stages. In advanced or metastatic liver tumors, systemic therapies such as sorafenib are the standard approach. Selective intra-arterial radionuclide therapy offers a promising treatment for inoperable liver tumors by delivering beta-emitting radiolabeled microspheres directly to tumor sites via the liver’s dual blood supply. However, the high cost of standard yttrium-90 microspheres has limited accessibility for patients. The current project aims to develop, optimize, and validate indigenously prepared microspheres for radiolabeling with Rhenium-188 from commercially available generators and indigenously produced Lutetium-177 from BARC Mumbai for selective internal radiation therapy in liver cancer. This multicentric study has high transformational potential, offering a safe, effective, and low-cost SIRT solution suitable for low-income settings. Through collaboration across multiple centers, the efficacy of microspheres labeled with both radionuclides will be evaluated. By establishing these accessible SIRT options, the project aims to reduce financial barriers to treatment, advance the goals of Jai Anusandhan in building innovative therapeutics through collaborative research, and improve outcomes for patients with limited treatment options. |