Clinical trial NCT05880472: Percutaneous Holmium Injection in Pancreatic Cancer
Official title: Percutaneous Intratumoural Holmium Microspheres Brachytherapy for Patients With Pancreatic Cancer; a Single Centre, Prospective Safety and Feasibility Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Pancreas Cancer
Keywords: Intratumoral therapy
Brachytherapy
Holmium-166
Holmium-166 microspheres
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: Quirem Medical B.V.
name: Terumo Medical Corporation
First posted: 2023-05-30
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Average tumour dose (Gy) by SPECT/CT
timeFrame: Within 24 hours post-intervention
measure: Number of adverse event per patient per grade by CTCAE v5.0
timeFrame: Up to 16 weeks post-intervention
Secondary outcomes:
measure: Average tumour dose (Gy) by MRI quantification
timeFrame: <24 hour and 16 weeks post-intervention
measure: Average tumour dose (Gy)by CT quantification
timeFrame: <24 hour and 16 weeks post-intervention
measure: Microsphere distribution (percentage covered) of 3D target area
timeFrame: <24 hour and 16 weeks post-intervention
measure: Injection percentage (%)
timeFrame: Immediately after the intervention
measure: Needle tip position off-target (mm)
timeFrame: Immediately after the intervention
measure: Operator hand and total body dose (mSv)
timeFrame: Immediately after the intervention
Other outcomes:
measure: Tumor response by RECIST 1.1
timeFrame: 16 weeks post-intervention
measure: Pain-scale assessment by Numeric Pain Rating Scale (NRS)
timeFrame: Up to 16 weeks post-intervention
measure: Implantation experience by questionnaire to the operator
timeFrame: Immediately after the intervention
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre
state: Gelderland
Study officials:
affiliation: Radboud University Medical Center
name: Frank Nijsen, PhD
role: PRINCIPAL_INVESTIGATOR
References: