Neoplasms

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Head and Neck Neoplasms

Xerostomia

Mouth Neoplasms

Salivary Gland Diseases

Mouth Diseases

Stomatognathic Diseases

Oral Cancer

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Everolimus

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Participants receive everolimus PO QD for 5 days beginning 2 weeks after radiation treatment. Participants also undergo saliva output testing at baseline prior to radiation or chemoradiation treatment, after 3 weeks of RT/chemoRT, after 6 weeks of RT/chemoRT, prior to everolimus administration, at completion of the 5 day everolimus course, and at 1, 3, and 6 months after the completion of radiation or chemoradiation therapy.

Laboratory Biomarker Analysis

Survey Administration

Panayiotis Savvides

This early phase 1 trial studies the use of everolimus in restoring salivary gland function in participants with locally advanced head and neck cancer after concurrent chemoradiation or radiation therapy alone.

PRIMARY OBJECTIVES:

I. To describe the recovery of salivary gland function after administration of a 5-day course of everolimus, administered two weeks after completion of radiation or chemoradiation therapy.

SECONDARY OBJECTIVES:

I. To describe the decrease of saliva flow rates during radiation or chemoradiation therapy.

II. To describe the changes in saliva protein composition during radiation or chemoradiation therapy and following administration of a 5-day course of everolimus.

OUTLINE: This is an early phase 1 proof of principal study.

Participants receive everolimus orally (PO) once daily (QD) for 5 days beginning 2 weeks after completion of radiation or chemoradiation treatment. Participants also undergo saliva output testing at baseline prior to radiation or chemoradiation treatment, after 3 weeks of RT/chemoRT, after 6 weeks of RT/chemoRT, prior to everolimus administration, at completion of the 5 day everolimus course, and at 1, 3, and 6 months after the completion of radiation or chemoradiation therapy.

Everolimus in Restoring Salivary Gland Function in Participants With Locally Advanced Head and Neck Cancer Treated With Radiation Therapy

Clinical Evaluation of Everolimus (a Rapamycin Analog) in Restoring Salivary Gland Function to Patients Treated With Radiotherapy for Head and Neck Cancer

The primary end point of the analysis will be the percent recovery of salivary gland function, with pre-everolimus treatment saliva flow rate as the denominator and the saliva flow rate at 3 months after completion of radiation or chemoradiation therapy as the numerator.

This will be measured during radiotherapy treatment at 3, 6 weeks, and prior to everolimus administration and the subsequent recovery of saliva flow rates at completion of the 5 day everolimus course and 1, 3 and 6 months after radiation therapy/chemoradiation therapy completion to determine the kinetics and stability of saliva flow rate recovery. Will be explored using graphical methods.

Protein composition within the saliva will be measured and will be expressed as percent decrease and recovery of amylase at all available time points. Will be explored using graphical methods.

Will be explored using graphical methods. Subjective assessment of salivary dysfunction. • Scale ranges: not difficult at all - very difficult. • Not difficult at all is considered better, very difficult is considered worse. Subscales are summed. Scale ranges: 1-5 = • 1 (Never), 2 (hardly ever), 3 (occasionally), 4 (fairly often), 5 (very often). • Sub scales are summed.

Will be explored using graphical methods. Measures xerostomia symptoms.

National Cancer Institute (NCI)

University of Arizona

Symptoms and General Pathology

Musculoskeletal Diseases

Eye Diseases

Skin and Connective Tissue Diseases

Immune System Diseases

Syndrome

Sjogren's Syndrome

Graft vs Host Disease

Arthritis

Arthritis, Rheumatoid

Joint Diseases

Rheumatic Diseases

Collagen Diseases

Dry Eye Syndromes

Keratoconjunctivitis Sicca

Lacrimal Apparatus Diseases

Connective Tissue Diseases

Autoimmune Diseases

Homologous Wasting Disease

This study will examine whether transplanted stem cells can turn into salivary gland cells in stem cell recipients. If so, stem cells might be used to restore salivary gland function in patients with Sjogren's syndrome and other causes of dry mouth. People with severe dry mouth may develop difficulty swallowing, severe tooth decay, infections of the mouth and pharynx, and mouth sores.

Female patients 18 years of age and older who are enrolled in the National Heart, Lung and Blood Institute's protocol 97-H-009 or 97-H-0202 and who have received a stem cell transplant from a male donor may be eligible for this study. Five patients with graft-versus host disease (GVHD) and five without GVHD will be included. GVHD is a transplantation reaction in which the donor's cells mount an immune response against the recipient's tissues. Patients with chronic GVHD have mouth ulcerations and dry mouth similar to that of patients with Sjogren's syndrome. Five healthy female volunteers will also be enrolled.

Participants will have a medical and dental history. Then, cells will be collected from the inside of the cheek (buccal cell scraping) and from the salivary glands (labial gland biopsy) as described below:

Buccal cell scraping - Cells are collected from the inside of the cheek by wiping for 5 seconds with a plastic brush.

Labial glands biopsy - The lower lip will be numbed and a small incision will be made on the inside of the lower lip. Six small salivary glands in the lower lip will be removed and the incision will be closed with four stitches.

Cells collected from these procedures will be examined to see if donated stem cells turned into salivary gland or cheek cells.

Patients will return to the clinic 5 to 10 days after the biopsy to have the stitches removed and assess healing.

Patients with Sjogren's syndrome (1-2 million in the U.S.), and patients exposed to ionizing radiation during therapy for head and neck cancer (\~40,000 new patients/year in the U.S.), experience severe salivary gland hypofunction. In both patient groups, via different pathogenic mechanisms, acinar cells in the glands are lost. These cells are the sole site of fluid production in salivary glands, and such patients cannot produce adequate levels of saliva, leading to considerable morbidity (xerostomia, dysphagia, dental caries, oro-pharyngeal infections, and mucositis). In many patients, all parenchymal tissue may be lost. For this latter group, there is no available therapy as they are not candidates for either pharmacological or gene therapy if little to no epithelial tissue remains. Recent reports suggest that organ-specific stem cells can differentiate into cells of other organs. These findings carry significant implications for possible clinical use. This protocol will investigate if adult human hematopoietic stem cells (HSC) can transdifferentiate into salivary gland and oral mucosal epithelial cells. We will recruit female bone marrow transplant recipients (from existing NHLBI protocols) who have received HSC from a male donor. This gender-mismatched strategy will allow us to detect cells of donor origin by using an RNA probe specific to the human Y chromosome. A biopsy of labial minor salivary glands and a cheek scraping will be obtained from female transplant patients. The biopsy causes minimal discomfort and the cheek scraping is a non-invasive technique. Both procedures are used routinely for clinical diagnosis. The samples will be co-stained for specific genetic and protein markers for salivary gland or oral mucosal epithelial cells, respectively. Cells positive for these markers (Y chromosome, cytokeratins, mucin 1, and NKCC1) would indicate that the donor's HSC became functionally competent salivary gland epithelial cells. This protocol will also examine bone marrow transplant recipients with chronic Graft-versus-Host Disease (GVHD). These patients show similar complications (xerostomia and oral mucositis) as those encountered in patients with Sjogren's Syndrome. We hypothesize that GVHD may provide a positive recruitment signal for HSC to home to salivary and oral mucosal sites. This protocol will recruit 5 female bone marrow transplant recipients without GVHD and 5 with GVHD. The primary potential benefit of this study is that if HSC can turn into salivary gland cells, they could be used to regenerate lost salivary gland tissues or to seed an artificial salivary gland for patients with irreversible salivary gland damage.

Potential of Transplanted Stem Cells to Mature Into Salivary Gland and Cheek Cells

Assessment of the Potential of Hematopoietic Stem Cells to Transdifferentiate Into Salivary Gland and Oral Mucosal Epithelial Cells in Adult Bone Marrow Transplant Patients

National Institute of Dental and Craniofacial Research (NIDCR)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Everolimus in Restoring Salivary Gland Function in Participants With Locally Advanced Head and Neck Cancer Treated With Radiation Therapy	NCT03578432	Salivary Gland ... Xerostomia Head and Neck C...	Everolimus Laboratory Biom... Survey Administ...	18 Years - 75 Years	University of Arizona
Potential of Transplanted Stem Cells to Mature Into Salivary Gland and Cheek Cells	NCT00023491	Graft vs Host D... Sjogren's Syndr...		-	National Institutes of Health Clinical Center (CC)

Spots Global Cancer Trial Database for salivary gland dysfunction