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Submandibular Gland Stem Cell Transplantation (RESTART)

Primary Purpose

Head and Neck Cancer

Status
Recruiting
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Submandibular Gland Stem Cell Transplantation
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Head and Neck Cancer focused on measuring Radiotherapy, Cell transplantation, Stem cell therapy

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • UMCGRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Transplantation

Arm Description

Submandibular Gland Stem Cell Transplantation

Outcomes

Primary Outcome Measures

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).
Feasibility: salivary flow rate
The salivary flow rate of the remaining submandibular gland will be recorded.

Secondary Outcome Measures

Salivary flow recovery
Unstimulated whole saliva, paraffin stimulated whole saliva and 5% citric acid stimulated parotid and submandibular/sublingual saliva measurements.
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.
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).
Overall survival and disease-free survival
Rate of water diffusion in remaining submandibular gland
The rate of water diffusion in remaining submandibular gland derived from DWI/DTI-MRI.
Amount of PSMA
The amount of prostate specific membrane antigen (PSMA) in the remaining submandibular gland derived from PET-CT

Full Information

First Posted
September 4, 2020
Last Updated
May 24, 2022
Sponsor
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT04593589
Brief Title
Submandibular Gland Stem Cell Transplantation
Acronym
RESTART
Official Title
Autologous Transplantation of Adult Salivary Gland Stem Cells to Restore Submandibular Gland Function After Radiotherapy
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
May 10, 2022 (Actual)
Primary Completion Date
May 10, 2024 (Anticipated)
Study Completion Date
May 10, 2029 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen

4. Oversight

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

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Head and Neck Cancer
Keywords
Radiotherapy, Cell transplantation, Stem cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Transplantation
Arm Type
Experimental
Arm Description
Submandibular Gland Stem Cell Transplantation
Intervention Type
Other
Intervention Name(s)
Submandibular Gland Stem Cell Transplantation
Intervention Description
Autologous transplantation of salivary stem cells (salisphere derived cells) cultured in vitro as obtained from submandibular glands after postoperative radiotherapy
Primary Outcome Measure Information:
Title
Safety: adverse events
Description
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).
Time Frame
Data for assessing safety will be recorded from day 1 to 365.
Title
Feasibility: salivary flow rate
Description
The salivary flow rate of the remaining submandibular gland will be recorded.
Time Frame
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 Measure Information:
Title
Salivary flow recovery
Description
Unstimulated whole saliva, paraffin stimulated whole saliva and 5% citric acid stimulated parotid and submandibular/sublingual saliva measurements.
Time Frame
Saliva measurements at 6 and 12 months and then on a yearly basis until 5 years after postoperative (chemo)radiation
Title
Impact of transplantation
Description
Patient-rated outcome measures including various side effects related to the postoperative (chemo)radiation and Quality of Life (QoL) using internationally validated questionnaires.
Time Frame
Patient-rated outcome measures at 6 and 12 months and then on a yearly basis until 5 years after postoperative (chemo)radiation
Title
Locoregional control
Description
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).
Time Frame
5 years after postoperative (chemo)radiation
Title
Overall survival and disease-free survival
Time Frame
5 years after postoperative (chemo)radiation
Title
Rate of water diffusion in remaining submandibular gland
Description
The rate of water diffusion in remaining submandibular gland derived from DWI/DTI-MRI.
Time Frame
6 and 12 months after postoperative (chemo)radiation
Title
Amount of PSMA
Description
The amount of prostate specific membrane antigen (PSMA) in the remaining submandibular gland derived from PET-CT
Time Frame
6 and 12 months after autologous stem cell transplantation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
R.J.H.M. Steenbakkers, MD, PhD
Phone
+31 (0)503610034
Email
r.steenbakkers@umcg.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R.J.H.M. Steenbakkers, MD, PhD
Organizational Affiliation
UMC Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
UMCG
City
Groningen
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
R.J.H.M. Steenbakkers, MD,PhD

12. IPD Sharing Statement

Learn more about this trial

Submandibular Gland Stem Cell Transplantation

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