Submandibular Gland Stem Cell Transplantation

Head and Neck Cancer Clinical Trial

— RESTART  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04593589
• Other study ID #: RT2020-04
• Secondary ID: NL75095.000.20
• Status: Recruiting
• Phase: Phase 1
• Start date: May 10, 2022
• Est. completion date: May 10, 2029

Study information

• Verified date: February 2024
• Source: University Medical Center Groningen
• Contact: R.J.H.M. Steenbakkers, MD, PhD
• Phone: +31 (0)503610034
• Email: r.steenbakkers[@]umcg.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: May 10, 2029
• Est. primary completion date: May 10, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms

Intervention

Other:
• Submandibular Gland Stem Cell Transplantation
Autologous transplantation of salivary stem cells (salisphere derived cells) cultured in vitro as obtained from submandibular glands after postoperative radiotherapy

Locations

Country	Name	City	State
Netherlands	UMCG	Groningen

Sponsors (1)

Lead Sponsor	Collaborator
University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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	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
Secondary	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
Secondary	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
Secondary	Overall survival and disease-free survival		5 years after postoperative (chemo)radiation
Secondary	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
Secondary	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