Percutaneous Holmium Injection in Pancreatic Cancer

Study Overview
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Brief Summary
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This investigator initiated study with a medical device aims to assess the safety and feasibility of percutaneous injected holmium-166 microsphere brachytherapy in patients with irresectable pancreatic cancer.

Detailed Description
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Objective: To test the feasibility and safety of minimally invasive CT-guided percutaneous holmium-166 microsphere brachytherapy in patients suffering from irresectable pancreatic cancer. Study design: This is a single centre, prospective, safety and feasibility study with a medical device in a maximum of 6 patients. Study population: Patients diagnosed with pathologically proven pancreatic adenocarcinoma, who are ineligible for exploratory surgery or surgical resection of the tumour after 8 cycles of systemic therapy or less in case of unacceptable toxicity, patient refusal or patients who are ineligible for systematic therapy. Intervention (if applicable): A radioactive medical device will be implanted by CT-guided percutaneous injection. The medical device in question are beta-minus (β-) and gamma(γ) emitting holmium-166 poly(L-lactic acid) microspheres (166Ho-PLLA-MS, HoMS) in a 0.1% Pluronic or cellulose based suspension. Main study parameters/endpoints: The main endpoint is to establish the feasibility and safety of CT-guided percutaneous intratumoural implantation of HoMS in irresectable pancreatic adenocarcinoma. Feasibility is established by evaluating the average tumour absorbed dose in Gray (Gy) calculated on SPECT and comparing to the pre-operative planning. Intratumoural microsphere distribution, absorbed tumour dose and non-target absorbed tumour dose are analysed using MRI and CT quantification. Safety is evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0), events deemed 'unlikely', 'probably' or 'definitely' related to the implantation procedure or implanted medical device. As exploratory endpoints, tumour response (RECIST1.1), pain (NRS) and Quality of Life is evaluated. Total follow-up is 16 weeks.

Official Title
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Percutaneous Intratumoural Holmium Microspheres Brachytherapy for Patients With Pancreatic Cancer; a Single Centre, Prospective Safety and Feasibility Study

Conditions
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Pancreas Cancer

Intervention / Treatment
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* Device: Intratumoral


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male aged 18 years and over. Pathologically proven pancreatic adenocarcinoma, also known as pancreatic ductal adenocarcinoma. Patient is deemed ineligible for surgical resection of the pancreatic cancer: in accordance with consensus at the multidisciplinary meetings/discussions, and/or the patient refuses to undergo surgical resection out of personal choice Life expectancy of 16 weeks or longer. World Health Organisation (WHO) Performance status 0-1 One or more measurable pancreatic tumours of at least 20 mm in the longest diameter by spiral CT or MRI according to the Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria. Negative pregnancy test for women of childbearing potential. Exclusion Criteria: Radiation therapy within the last 4 weeks before the start of study therapy. Chemotherapy within the last 2 weeks before the start of study therapy. Calcifications in the pancreas or tumour that are highly expected to obstruct the needle tract Any unresolved toxicity ≥ grade 3 from the National Cancer Institute (NCI), Common Terminology Criteria for Adverse Events (CTCAE version 5.0) from previous anti-cancer therapy. Leukocytes < 3.0 10^9/l and/or platelet count < 75 10^9/l. Kidney failure: Creatine > 165 µmol/l and/or eGFR < 60 ml/min/1,73m^2 Significant cardiac event (e.g. myocardial infarction, superior vena cava (SVC) syndrome, New York Heart Association (NYHA) classification of heart disease ≥2 within 3 months before entry, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia. Patient is deemed ineligible for implantation of 166Ho by an expert panel (surgeon, nuclear medicine physician, interventional radiologist, radiologist, and researcher) due to tumour anatomy, nearby structures, patient status or a combination. Pregnancy or breast feeding (women of child-bearing potential). Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression. Patients who are declared incompetent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention arm<br>Single or multiple injections of holmium-166 microspheres (up to 150 Gy) in a single session. Intervention is not repeated. | Device: Intratumoral<br>* Comparable to CE-marked QuiremSpheres(R) outside of intended use with minor altered specification.<br>* Other names: Intratumoural holmium-166 microspheres;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average tumour dose (Gy) by SPECT/CT | Tumour and non-tumour dose is estimated by SPECT using after intervention to assess feasibility. | Within 24 hours post-intervention | 
| Number of adverse event per patient per grade by CTCAE v5.0 | Number and grade of adverse events per patient by Common Terminology Criteria for Adverse Events (CTCAE v5.0) deemed 'unlikely', 'probably', or 'definitely' related to the implantation procedure or medical device implanted. | Up to 16 weeks post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average tumour dose (Gy) by MRI quantification |  | <24 hour and 16 weeks post-intervention | 
| Average tumour dose (Gy)by CT quantification |  | <24 hour and 16 weeks post-intervention | 
| Microsphere distribution (percentage covered) of 3D target area | By CT or MRI to assess dose coverage | <24 hour and 16 weeks post-intervention | 
| Injection percentage (%) | Implant efficiency | Immediately after the intervention | 
| Needle tip position off-target (mm) | implant accuracy | Immediately after the intervention | 
| Operator hand and total body dose (mSv) | Operator safety | Immediately after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Intratumoral therapy, Brachytherapy, Holmium-166, Holmium-166 microspheres