Allogeneic Mesenchymal Stem Cells for Radiation-induced Hyposalivation and Xerostomia/Dry Mouth

A Phase I Open Label Study Evaluating the Safety and Feasibility of Allogeneic Mesenchymal Stem Cells for Radiation-induced Hyposalivation and Xerostomia in Previous Oropharynx Cancer Patients

An investigator-initiated, non-randomized, open label study to investigate the safety, feasibility and tolerability of intraglandular injection of allogeneic mesenchymal stem/stromal cells (MSCs) into the submandibular and parotid glands of the patients with radiation-induced hyposalivation and xerostomia after radiation for a oropharyngeal squamous cell carcinoma

Patients with previous oropharyngeal cancer and radiation-induced hyposalivation and xerostomia (dry mouth syndrome) will receive intraglandular injections of allogeneic adipose-derived MSCs into the submandibular and parotid glands. The trial will be Good Clinical Practice (GCP) Monitored. From healthy donors, MSCs will be produced at a Good Manufacturing Practice (GMP) Facility.

The patients will be followed for four months for safety, tolerability, and efficacy registration. Changes in quality of life, unstimulated, and stimulated whole saliva flow rate, salivary gland function will be assessed. Immune response towards receiving allogeneic MSCs will be evaluated in plasma and saliva. Changes in the composition and quality of the whole saliva will be investigated.

Saliva from the participants will altså be compared to saliva from ten healthy controls.

Inclusion Criteria:

1. Age between 18-75 years
2. Previous radiotherapy +/- chemotherapy for OPSCC stage I- II (UICC-8, 2017)
3. 2 years' follow-up without recurrence
4. Clinically reduced salivation and hyposalivation, evaluated by a screening
5. Unstimulated salivary flow rate between 0.2mL/min and 0.05mL/min
6. Grade 2-3 xerostomia (CTCAEv5.0)
7. WHO Performance status (PS) 0-1
8. Informed consent

Exclusion Criteria:

1. Any cancer in the previous 4 years (not including OPSCC and basocellular carcinomas)
2. Xerogenic medications
3. Penicillin or Streptomycin allergy
4. Any other diseases of the salivary glands, e.g. Sjögren's syndrome or sialolithiasis
5. Previous parotid or submandibular gland surgery
6. Previous treatment with any type of stem cells
7. Breastfeeding, Pregnancy or planned pregnancy within the next 2 years
8. Smoking within the previous 6 months.
9. Alcohol abuse (consumption must not exceed 7 units/week for women and 14 units/week for men (Danish National board health alcohol guidelines3)
10. Any other disease/condition judged by the investigator to be grounds for exclusion