Submandibular Gland Stem Cell Transplantation (RESTART)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Cancer
• Intervention / Treatment: Other: Submandibular Gland Stem Cell Transplantation

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: R.J.H.M. Steenbakkers, MD, PhD; Phone Number: +31 (0)503610034; Email: r.steenbakkers@umcg.nl

Study Locations

• Netherlands
  • Groningen, Netherlands
    • Recruiting
    • UMCG
    • Contact: R.J.H.M. Steenbakkers, MD,PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Transplantation; Submandibular Gland Stem Cell Transplantation	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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medical Center Groningen
• Investigators: Principal Investigator: R.J.H.M. Steenbakkers, MD, PhD, UMC Groningen

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Estimated): May 10, 2024
• Study Completion (Estimated): May 10, 2029

Study Registration Dates

• First Submitted: September 4, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 20, 2020

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Radiotherapy; Stem cell therapy; Cell transplantation
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms
• Other Study ID Numbers: RT2020-04; NL75095.000.20 (Registry Identifier: CCMO register)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No