Percutaneous Holmium Injection in Pancreatic Cancer

Pancreas Cancer Clinical Trial

— SLOTH-2a  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05880472
• Other study ID #: NL.82292.091.22
• Status: Recruiting
• Phase: N/A
• Start date: May 2023
• Est. completion date: May 2024

Study information

• Verified date: May 2023
• Source: Radboud University Medical Center
• Contact: Ysbrand CY Willink, MSc
• Phone: +312436-13651
• Email: Ysbrand.Willink[@]radboudumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 6
• Est. completion date: May 2024
• Est. primary completion date: January 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreas Cancer
• Pancreatic Neoplasms

Intervention

Device:
• Intratumoral
Comparable to CE-marked QuiremSpheres(R) outside of intended use with minor altered specification.

Locations

Country	Name	City	State
Netherlands	Radboud University Medical Centre	Nijmegen	Gelderland

Sponsors (3)

Lead Sponsor	Collaborator
Radboud University Medical Center	Quirem Medical B.V., Terumo Medical Corporation

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tumor response by RECIST 1.1		16 weeks post-intervention
Other	Pain-scale assessment by Numeric Pain Rating Scale (NRS)	Scale from 0 to 10 of average and worst pain with 0 no pain and 10 worst possible pain	Up to 16 weeks post-intervention
Other	Implantation experience by questionnaire to the operator		Immediately after the intervention
Primary	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
Primary	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	Average tumour dose (Gy) by MRI quantification		<24 hour and 16 weeks post-intervention
Secondary	Average tumour dose (Gy)by CT quantification		<24 hour and 16 weeks post-intervention
Secondary	Microsphere distribution (percentage covered) of 3D target area	By CT or MRI to assess dose coverage	<24 hour and 16 weeks post-intervention
Secondary	Injection percentage (%)	Implant efficiency	Immediately after the intervention
Secondary	Needle tip position off-target (mm)	implant accuracy	Immediately after the intervention
Secondary	Operator hand and total body dose (mSv)	Operator safety	Immediately after the intervention