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

Xerostomia Following Radiotherapy Clinical Trial

Official title:

Treatment of Post-radiation Xerostomia With Allogeneic Mesenchymal Stromal Stem Cells: a Pilot Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06012604
• Other study ID #: ERIDNPVO-0038/2023
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: September 2023
• Est. completion date: August 2025

Study information

• Verified date: August 2023
• Source: Institute of Oncology Ljubljana
• Contact: Primož Strojan, Prof.
• Phone: +38615879290
• Email: pstrojan[@]onko-i.si
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: August 2025
• Est. primary completion date: August 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Xerostomia
• Xerostomia Following Radiotherapy

Intervention

Biological:
• allogeneic mesenchymal stromal stem cells
mesenchymal stromal stem cells injection under ultrasound guidance into parotid and submandibular glands

Locations

Country	Name	City	State
Slovenia	Blood Transfusion Center of Slovenia	Ljubljana
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Slovenia	University Clinical Center Ljubljana	Ljubljana
Slovenia	University of Ljubljana	Ljubljana

Sponsors (4)

Lead Sponsor	Collaborator
Institute of Oncology Ljubljana	Blood Transfusion Centre of Slovenia, University Medical Centre Ljubljana, University of Ljubljana

Country where clinical trial is conducted

Slovenia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety: Number of patients with serious adverse events	Registration of number of patients with serious adverse events in a 4 months follow-up period	4 months
Secondary	Efficacy: Change in unstimulated and stimulated whole salivary flow rate	Flow rates assessed by sialometry	4 months
Secondary	Efficacy: Change in saliva composition	Change in saliva composition	4 months
Secondary	Efficacy: Change in subjective assessment of xerostomia	Change in subjective assessment of xerostomia evaluated by Visual Analog Scale (VAS) questionnaire	4 months
Secondary	Efficacy: Change in quality of life	Change in quality of life evaluated by QLQ-H&N-35 questionnaire	at baseline and 4 weeks and 4 months after intervention
Secondary	Efficacy: performance of MSCs application	Assessed by salivary gland scintigraphy with [99mTc]Tc-HMPAO labeled MSCs	4 months
Secondary	Efficacy: Salivary gland function	Assessed by salivary gland scintigraphy with pertechnetate ([99mTc]TcO4-)	4 months
Secondary	Efficacy: salivary gland appearance	Assessed by magnetic resonance imaging and ultrasonography	4 months
Secondary	Efficacy: salivary gland structure	Assessed by histopathological examination of salivary gland tissue sample	4 months