Percutaneous Holmium Injection in Pancreatic Cancer (SLOTH-2a)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Pancreas Cancer
• Intervention / Treatment: Device: Intratumoral

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6525GA
      • Radboud University Medical Centre

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female or male aged 18 years and over.
2. Pathologically proven pancreatic adenocarcinoma, also known as pancreatic ductal adenocarcinoma.

3. Patient is deemed ineligible for surgical resection of the pancreatic cancer:

   1. in accordance with consensus at the multidisciplinary meetings/discussions,
   2. and/or the patient refuses to undergo surgical resection out of personal choice
4. Life expectancy of 16 weeks or longer.
5. World Health Organisation (WHO) Performance status 0-1
6. 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.
7. Negative pregnancy test for women of childbearing potential.

Exclusion Criteria:

1. Radiation therapy within the last 4 weeks before the start of study therapy.
2. Chemotherapy within the last 2 weeks before the start of study therapy.
3. Calcifications in the pancreas or tumour that are highly expected to obstruct the needle tract
4. 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.
5. Leukocytes < 3.0 10^9/l and/or platelet count < 75 10^9/l.
6. Kidney failure: Creatine > 165 µmol/l and/or eGFR < 60 ml/min/1,73m^2
7. 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.
8. 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.
9. Pregnancy or breast feeding (women of child-bearing potential).
10. Patients suffering from psychic disorders that make a comprehensive judgement impossible, such as psychosis, hallucinations and/or depression.
11. Patients who are declared incompetent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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) between grade 0 (mild complication) to grade 5 (death) 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation experience by questionnaire to the operator		Immediately after the intervention
Tumor response by RECIST 1.1	Tumor response by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST). Response is categorised by complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD).	16 weeks post-intervention
Pain-scale assessment by Numeric Pain Rating Scale (NRS)	Numeric (Pain) Rating Scale from average and worst pain in past week with 0 = no pain and 10 = worst possible pain	Up to 16 weeks post-intervention

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Terumo Medical Corporation; Quirem Medical B.V.
• Investigators: Principal Investigator: Frank Nijsen, PhD, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): April 22, 2025
• Study Completion (Estimated): April 22, 2025

Study Registration Dates

• First Submitted: May 9, 2023
• First Submitted That Met QC Criteria: May 19, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Brachytherapy; Holmium-166; Intratumoral therapy; Holmium-166 microspheres
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: NL.82292.091.22

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No