Submandibular Gland Stem Cell Transplantation

Study Overview
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Brief Summary
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This study is a phase I safety and feasibility study to treat head and neck cancer patients with autologous salivary gland stem cell transplantation after postoperative (chemo)radiotherapy.

Official Title
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Autologous Transplantation of Adult Salivary Gland Stem Cells to Restore Submandibular Gland Function After Radiotherapy

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Other: Submandibular Gland Stem Cell Transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Squamous cell carcinoma (SCC) originating from the mucosa of the oral cavity; Primary resection of tumour including an electively or therapeutic ipsilateral neck dissection (at least levels Ib to III, including the submandibular gland). Postoperative radiotherapy or chemoradiation, including prophylactic or therapeutic irradiation of the contralateral side of the neck (where the remaining submandibular gland is), including at least levels Ib to IV), next to irradiation of the tumour bed and ipsilateral neck (current standard); Age ≥ 18 years; WHO performance 0-2; Written informed consent; Exclusion Criteria: Primary (definitive) radiotherapy, with or without systemic treatment; Previous radiotherapy of the head and neck region (re-irradiation); Positive microbiological screening for Human Immunodeficiency Virus type 1 and 2, hepatitis B and C virus and Treponema pallidum. Presence of systemic disease known to affect salivary gland functioning (e.g., Sjögren's syndrome); Known allergy to mice and gentamicin History within the past five years of malignancies other than: basal or squamous cell carcinoma of the skin in situ carcinoma of the cervix; Females who are pregnant or lactating at entry.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transplantation<br>Submandibular Gland Stem Cell Transplantation | Other: Submandibular Gland Stem Cell Transplantation<br>* Autologous transplantation of salivary stem cells (salisphere derived cells) cultured in vitro as obtained from submandibular glands after postoperative radiotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: adverse events | The number of adverse events (AE), serious adverse events (SAE) or suspected unexpected adverse reactions (SUSAR) after autologous salivary stem cell transplantation. All possible adverse events will be scored according to the definitions of the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4.0). | Data for assessing safety will be recorded from day 1 to 365. | 
| Feasibility: salivary flow rate | The salivary flow rate of the remaining submandibular gland will be recorded. | Data for assessing feasibility will be recorded 6 and 12 months after autologous stem cell transplantation to assess if salivary flow will be increased compared to salivary flow before transplantation. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Salivary flow recovery | Unstimulated whole saliva, paraffin stimulated whole saliva and 5% citric acid stimulated parotid and submandibular/sublingual saliva measurements. | Saliva measurements at 6 and 12 months and then on a yearly basis until 5 years after postoperative (chemo)radiation | 
| Impact of transplantation | Patient-rated outcome measures including various side effects related to the postoperative (chemo)radiation and Quality of Life (QoL) using internationally validated questionnaires. | Patient-rated outcome measures at 6 and 12 months and then on a yearly basis until 5 years after postoperative (chemo)radiation | 
| Locoregional control | Locoregional control is defined as the number of patients with recurrent disease within or adjacent to the primary tumor site and regional lymph nodes after postoperative (chemo)radiation, assessed by pathology and/or oncologic imaging (CT, MRI or PET). | 5 years after postoperative (chemo)radiation | 
| Overall survival and disease-free survival |  | 5 years after postoperative (chemo)radiation | 
| Rate of water diffusion in remaining submandibular gland | The rate of water diffusion in remaining submandibular gland derived from DWI/DTI-MRI. | 6 and 12 months after postoperative (chemo)radiation | 
| Amount of PSMA | The amount of prostate specific membrane antigen (PSMA) in the remaining submandibular gland derived from PET-CT | 6 and 12 months after autologous stem cell transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Radiotherapy, Cell transplantation, Stem cell therapy