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Treatment of Post-radiation Xerostomia With Allogeneic Mesenchymal Stromal Stem Cells

Primary Purpose

Xerostomia Following Radiotherapy

Status
Not yet recruiting
Phase
Phase 1
Locations
Slovenia
Study Type
Interventional
Intervention
allogeneic mesenchymal stromal stem cells
Sponsored by
Institute of Oncology Ljubljana
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Xerostomia Following Radiotherapy focused on measuring post-radiation xerostomia, allogenic mesenchyma stromal stem cells, toxicity, effectiveness

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: squamous cell carcinoma of the oropharynx, Union for International Cancer Control TNM Classification of Malignant Tumors )8th ed.) clinical stage T1-2N+ or cT3-4cN0-3 M0, treated with curative intent radiotherapy (tumor dose 66-70 Gy, bilateral neck irradiation) with or without concurrent chemotherapy 2 years or more post-treatment without signs of locoregional recurrence or systemic metastasis non-smoker or former smoker (quit smoking ≥2 years ago) mean radiation dose >26 Gy to each of the parotid glands and >35 Gy to each of the submandibular glands xerostomia of grade 2 or 3, assessed according to the CTCAE v5.0 scale Clinically reduced salivary flow and hyposalivation (unstimulated whole saliva flow rate 0.05-0.20 ml/min) age between 18-75 years both sexes signed "Informed Consent Form" for participation in the study Exclusion Criteria: newly diagnosed malignancy anywhere in the body within the past two years active smoker use of medications with potential to cause dry mouth (e.g., tricyclic antidepressants, antipsychotics, decongestants, bronchodilators, antihypertensives like beta-blockers and diuretics, antihistamines, hypnotic sedatives, opioids, and muscle relaxants) other salivary gland diseases (e.g., Sjögren's syndrome, scleroderma, sialolithiasis, etc.) patients on anticoagulant therapy that cannot be discontinued during the intervention pregnancy or planned pregnancy within the next two years breastfeeding active, uncontrolled infection or other medical (including psychiatric) conditions that, in the researchers' opinion, do not allow for the safe administration of the planned therapy and performance of the follow-up procedures known substance abuse or alcoholism

Sites / Locations

  • Blood Transfusion Center of Slovenia
  • Institute of Oncology Ljubljana
  • University Clinical Center Ljubljana
  • University of Ljubljana

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

allogeneic mesenchymal stromal stem cells

Arm Description

Application of allogeneic mesenchymal stromal stem cells (MSC, derived from umbilical cord tissue) under ultrasound guidance into both parotid and submandibular glands.

Outcomes

Primary Outcome Measures

Safety: Number of patients with serious adverse events
Registration of number of patients with serious adverse events in a 4 months follow-up period

Secondary Outcome Measures

Efficacy: Change in unstimulated and stimulated whole salivary flow rate
Flow rates assessed by sialometry
Efficacy: Change in saliva composition
Change in saliva composition
Efficacy: Change in subjective assessment of xerostomia
Change in subjective assessment of xerostomia evaluated by Visual Analog Scale (VAS) questionnaire
Efficacy: Change in quality of life
Change in quality of life evaluated by QLQ-H&N-35 questionnaire
Efficacy: performance of MSCs application
Assessed by salivary gland scintigraphy with [99mTc]Tc-HMPAO labeled MSCs
Efficacy: Salivary gland function
Assessed by salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-)
Efficacy: salivary gland appearance
Assessed by magnetic resonance imaging and ultrasonography
Efficacy: salivary gland structure
Assessed by histopathological examination of salivary gland tissue sample

Full Information

First Posted
August 5, 2023
Last Updated
August 22, 2023
Sponsor
Institute of Oncology Ljubljana
Collaborators
Blood Transfusion Centre of Slovenia, University Medical Centre Ljubljana, University of Ljubljana
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1. Study Identification

Unique Protocol Identification Number
NCT06012604
Brief Title
Treatment of Post-radiation Xerostomia With Allogeneic Mesenchymal Stromal Stem Cells
Official Title
Treatment of Post-radiation Xerostomia With Allogeneic Mesenchymal Stromal Stem Cells: a Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
August 2025 (Anticipated)
Study Completion Date
August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institute of Oncology Ljubljana
Collaborators
Blood Transfusion Centre of Slovenia, University Medical Centre Ljubljana, University of Ljubljana

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The goal of this clinical trial is to learn about toxicity of allogeneic mesenchymal stromal stem cells (MSC, derived from umbilical cord tissue) treatment in head and neck cancer patients with for post-radiation xerostomia. The main question it aims to answer is the toxicity of intervention and the secondary objective is to assess preliminary efficacy. Participants will receive MSC in both parotid and submandibular glands: the toxicity of the intervention will be assessed using CTCAE v5.0 and its effect will be evaluated through measuring salivary flow and composition, radiologically (ultrasonography, magnetic resonance imaging), with scintigraphy and questionnaires. In the control group, salivary gland function (salivary flow and saliva composition) will be assessed for comparison with the intervention group.
Detailed Description
The aim of the study is to assess the safety and preliminary efficacy of treating xerostomia with allogeneic mesenchymal stromal stem cells (MSC) derived from umbilical cord tissue. This is a non-randomized, single-center, non-blinded Phase I study. There will be 10 patients in the intervention group and 10 healthy volunteers in the control group. In the intervention group, patients who were successfully treated with (chemo)radiotherapy for oropharyngeal squamous cell carcinoma two or more years ago and have xerostomia of grade 2 or 3 according to CTCAE v.5.0 will receive MSC injections under ultrasound guidance into both parotid and submandibular glands (1 ml syringe with 50×106 MSC and 0.5 ml syringe with 25×106 MSC). Before the application, measurements of unstimulated and stimulated saliva flow, saliva composition, and blood parameters (complete blood count, biochemical tests, prothrombin time, international normalized ratio) will be performed. Magnetic resonance imaging of the glands (to assess changes in volume, signal, and diffusivity), ultrasound elastography (to assess gland consistency), salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-, to evaluate radioisotope uptake in functioning parenchyma and excretory fraction of each gland) and scintigraphy with hexamethylpropyleneamine oxime ([99mTc]Tc-HMPAO)-labeled MSC (to assess distribution, retention, and migration of MSC from the site of application) will also be conducted, along with a biopsy from one of the four glands (to evaluate morphological changes in glandular tissue). Patients will complete two xerostomia questionnaires and a quality of life questionnaire European Organization for Research and Treatment of Cancer Quality of Life H&N35. On the 1st and 5th day after the intervention (day 0), patients will be examined, and toxicity will be assessed according to CTCAE v5.0. The effect of the intervention will be evaluated at 4 weeks and 4 months, repeating the tests performed before the intervention, with the exception of the biopsy and scintigraphy, which will be repeated only 4 months after the intervention (from the same gland as the first time). In the control group, healthy individuals will submit saliva samples to determine unstimulated and stimulated saliva flow and saliva composition (for comparison with the intervention group).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Xerostomia Following Radiotherapy
Keywords
post-radiation xerostomia, allogenic mesenchyma stromal stem cells, toxicity, effectiveness

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
intervention group control group
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
allogeneic mesenchymal stromal stem cells
Arm Type
Experimental
Arm Description
Application of allogeneic mesenchymal stromal stem cells (MSC, derived from umbilical cord tissue) under ultrasound guidance into both parotid and submandibular glands.
Intervention Type
Biological
Intervention Name(s)
allogeneic mesenchymal stromal stem cells
Intervention Description
mesenchymal stromal stem cells injection under ultrasound guidance into parotid and submandibular glands
Primary Outcome Measure Information:
Title
Safety: Number of patients with serious adverse events
Description
Registration of number of patients with serious adverse events in a 4 months follow-up period
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Efficacy: Change in unstimulated and stimulated whole salivary flow rate
Description
Flow rates assessed by sialometry
Time Frame
4 months
Title
Efficacy: Change in saliva composition
Description
Change in saliva composition
Time Frame
4 months
Title
Efficacy: Change in subjective assessment of xerostomia
Description
Change in subjective assessment of xerostomia evaluated by Visual Analog Scale (VAS) questionnaire
Time Frame
4 months
Title
Efficacy: Change in quality of life
Description
Change in quality of life evaluated by QLQ-H&N-35 questionnaire
Time Frame
at baseline and 4 weeks and 4 months after intervention
Title
Efficacy: performance of MSCs application
Description
Assessed by salivary gland scintigraphy with [99mTc]Tc-HMPAO labeled MSCs
Time Frame
4 months
Title
Efficacy: Salivary gland function
Description
Assessed by salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-)
Time Frame
4 months
Title
Efficacy: salivary gland appearance
Description
Assessed by magnetic resonance imaging and ultrasonography
Time Frame
4 months
Title
Efficacy: salivary gland structure
Description
Assessed by histopathological examination of salivary gland tissue sample
Time Frame
4 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: squamous cell carcinoma of the oropharynx, Union for International Cancer Control TNM Classification of Malignant Tumors )8th ed.) clinical stage T1-2N+ or cT3-4cN0-3 M0, treated with curative intent radiotherapy (tumor dose 66-70 Gy, bilateral neck irradiation) with or without concurrent chemotherapy 2 years or more post-treatment without signs of locoregional recurrence or systemic metastasis non-smoker or former smoker (quit smoking ≥2 years ago) mean radiation dose >26 Gy to each of the parotid glands and >35 Gy to each of the submandibular glands xerostomia of grade 2 or 3, assessed according to the CTCAE v5.0 scale Clinically reduced salivary flow and hyposalivation (unstimulated whole saliva flow rate 0.05-0.20 ml/min) age between 18-75 years both sexes signed "Informed Consent Form" for participation in the study Exclusion Criteria: newly diagnosed malignancy anywhere in the body within the past two years active smoker use of medications with potential to cause dry mouth (e.g., tricyclic antidepressants, antipsychotics, decongestants, bronchodilators, antihypertensives like beta-blockers and diuretics, antihistamines, hypnotic sedatives, opioids, and muscle relaxants) other salivary gland diseases (e.g., Sjögren's syndrome, scleroderma, sialolithiasis, etc.) patients on anticoagulant therapy that cannot be discontinued during the intervention pregnancy or planned pregnancy within the next two years breastfeeding active, uncontrolled infection or other medical (including psychiatric) conditions that, in the researchers' opinion, do not allow for the safe administration of the planned therapy and performance of the follow-up procedures known substance abuse or alcoholism
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Primož Strojan, Prof.
Phone
+38615879290
Email
pstrojan@onko-i.si
First Name & Middle Initial & Last Name or Official Title & Degree
Violeta Kaluža
Phone
+38615879122
Email
vkaluza@onko-i.si
Facility Information:
Facility Name
Blood Transfusion Center of Slovenia
City
Ljubljana
ZIP/Postal Code
SI-1000
Country
Slovenia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Urban Švajger, Prof.
Phone
+386 1 5438 391
Email
urban.svajger@ztm.si
First Name & Middle Initial & Last Name & Degree
Urban Švajger, Prof.
First Name & Middle Initial & Last Name & Degree
Nataša Tešić, Dr.
First Name & Middle Initial & Last Name & Degree
Katarina Hartman, Dr.
Facility Name
Institute of Oncology Ljubljana
City
Ljubljana
ZIP/Postal Code
SI-1000
Country
Slovenia
Facility Name
University Clinical Center Ljubljana
City
Ljubljana
ZIP/Postal Code
SI-1000
Country
Slovenia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Luka Ležaić, MD
Phone
+386 1 522 34 49
Email
luka.lezaic@kclj.si
First Name & Middle Initial & Last Name & Degree
Luka Ležaić, MD
First Name & Middle Initial & Last Name & Degree
Alkaž Sočan, PhD.
Facility Name
University of Ljubljana
City
Ljubljana
ZIP/Postal Code
SI-1000
Country
Slovenia

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Treatment of Post-radiation Xerostomia With Allogeneic Mesenchymal Stromal Stem Cells

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