Clinical trial NCT03874572: Allogeneic Mesenchymal Stem Cells for Radiation-induced Hyposalivation and Xerostomia/Dry Mouth
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Xerostomia Due to Radiotherapy
Hyposalivation
Xerostomia
Oropharynx Cancer
Salivary Gland Diseases
Dry Mouth
Mesenchymal Stem Cells
Mesenchymal Stromal Cells
Stem Cells
Keywords: Xerostomia Due to Radiotherapy
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2019-03-14
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Safety: Number of patients with serious adverse events
timeFrame: 4 months
Secondary outcomes:
measure: Immune reponse :Development of donor specific antibodies
timeFrame: 4 months
measure: Efficacy: Change in Unstimulated Whole Salivary flow rate
timeFrame: 4 months
measure: Efficacy: Change in Stimulated Whole Salivary flow rate
timeFrame: 4 months
measure: Efficacy: Change in quality of life
timeFrame: 4 months
measure: Efficacy: Salivary gland function
timeFrame: 4 months
measure: Efficacy: Change in Saliva composition
timeFrame: 4 months
measure: Efficacy: Change in Saliva Proteomics
timeFrame: 4 months
measure: Efficacy: Change in RNA in Saliva
timeFrame: 4 months
measure: Immune reponse
timeFrame: 4 months
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Department of Otolaryngology, Rigshospitalet, University Hospital of Copenhagen
city: Copenhagen
country: Denmark
facility: Department of Otolaryngology, Rigshospitalet
Study officials:
affiliation: Department of Otolaryngology, Rigshospitalet, University Hospital of Copenhagen
name: Charlotte Lynggaard, MD
role: PRINCIPAL_INVESTIGATOR
References: