Phase I Multicentric Dose-Escalation Study of Indigenous, Affordable Microspheres for Selective Internal Radiation Therapy (SIRT) in Patients with Unresectable Liver Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 5
- 主要终点
- 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.
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- None
入排标准
- 年龄范围
- 18.00 Year(s) 至 90.00 Year(s)（—）
- 性别
- All
入选标准
- •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: 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.
- •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.
排除标准
- •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.
结局指标
主要结局
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.
时间窗: Day 1-Day 28 post-SIRT
次要结局
- 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)
- 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)
- 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)
研究者
Dr Jaya Shukla
Postgraduate Institute of Medical Education and Research