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

NCT03578432 | Terminated Early Phase 1 DMC FDA Drug

• 4 other identifiers: PHXB-17-0072-70-15NCI-2018-00492CRAD001XUA274TP30CA023074
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Salivary Gland Dysfunction; Xerostomia; Head and Neck Cancer

Keywords

Xerostomia; Dry Mouth; Salivary Gland Dysfunction; Head and Neck Cancer; Mouth Cancer; Everolimus; Rapamycin; Neck Cancer; Saliva

Outcome Measures

Primary Outcomes (1)

• Percent recovery of salivary gland function

  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.

  At 3 months after completion of radiation or chemoradiation therapy

Secondary Outcomes (4)

• Change of saliva flow rates

  Up to 6 months after completion of radiation or chemoradiation therapy

• Saliva protein composition

  Up to 6 months after completion of radiation or chemoradiation therapy

• Total score obtained on Xerostomia Visual Analog Scale survey

  Up to 6 months after completion of radiation or chemoradiation therapy

• Total score obtained on Xerostomia Inventory Survey

  Up to 6 months after completion of radiation or chemoradiation therapy

Study Arms (1)

Supportive care (everolimus, saliva output testing)

EXPERIMENTAL

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.

Drug: Everolimus; Other: Laboratory Biomarker Analysis; Other: Survey Administration

Interventions

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Supportive care (everolimus, saliva output testing)

Laboratory Biomarker Analysis OTHER

Correlative studies

Supportive care (everolimus, saliva output testing)

Survey Administration OTHER

Ancillary studies

Supportive care (everolimus, saliva output testing)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Performance status Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L
• Platelets ≥ 100 x 10\^9/L
• Hemoglobin (Hgb) \> 9 g/dL
• Total serum bilirubin ≤ 2.0 mg/dL
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x upper limits of normal (ULN) (≤ 5 x ULN in patients with liver metastases)
• International normalized ratio (INR) ≤ 2
• Serum creatinine ≤ 1.5 x ULN
• Fasting serum cholesterol ≤ 300 mg/dL or ≤ 7.75 mmol/L and fasting triglycerides ≤ 2.5 x ULN
• NOTE: in case one or both of these thresholds are exceeded, the patient can only be included after initiation of appropriate lipid lowering medication
• Signed informed consent obtained prior to any screening procedures
• Patients with locally advanced squamous cell carcinoma of the head and neck, treated with curative intent either in the post-operative or definitive setting with high dose radiotherapy (≥ 50 Gy) with or without chemotherapy

You may not qualify if:

• Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks of the start of everolimus (including chemotherapy, radiation therapy, antibody based therapy, etc.)
• Known intolerance or hypersensitivity to everolimus or other rapamycin analogs (e.g. sirolimus, temsirolimus)
• Known impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral everolimus
• Uncontrolled diabetes mellitus as defined by glycated hemoglobin (HbA1c) \> 8% despite adequate therapy; patients with a known history of impaired fasting glucose or diabetes mellitus (DM) may be included, however blood glucose and antidiabetic treatment must be monitored closely throughout the trial and adjusted as necessary
• Patients who have any severe and/or uncontrolled medical conditions such as:
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction ≤ 6 months prior to start of everolimus, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease
• Symptomatic congestive heart failure of New York heart Association class III or IV
• Active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis (i.e. quantifiable hepatitis B virus \[HBV\]-deoxyribonucleic acid \[DNA\] and/or positive hepatitis B virus surface antigen \[HbsAg\], quantifiable hepatitis C virus \[HCV\]-ribonucleic acid \[RNA\])
• Known severely impaired lung function (spirometry and carbon monoxide diffusing capacity \[DLCO\] 50% or less of normal and oxygen \[O2\] saturation 88% or less at rest on room air)
• Active, bleeding diathesis
• Chronic treatment with corticosteroids or other immunosuppressive agents; topical or inhaled corticosteroids are allowed
• Known history of human immunodeficiency virus (HIV) seropositivity
• Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study; patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
• Patients who have a history of another primary malignancy, with the exceptions of: nonmelanoma skin cancer, and carcinoma in situ of the cervix, uteri, or breast from which the patient has been disease free for ≥ 3 years
• Patients with a history of non-compliance to medical regimens or who are considered potentially unreliable or will not be able to complete the entire study

Sponsors & Collaborators

• University of Arizona: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

The University of Arizona Cancer Center

Phoenix, Arizona, 85012, United States

Location

MeSH Terms

Conditions

Xerostomia; Head and Neck Neoplasms; Mouth Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Salivary Gland Diseases; Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Panayiotis Savvides

  The University of Arizona Cancer Center at Dignity Health St. Joseph's Hospital and Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2018
• First Posted: July 6, 2018
• Study Start: May 4, 2018
• Primary Completion: November 15, 2019
• Study Completion: November 15, 2019
• Last Updated: December 2, 2019

Record last verified: 2019-11

Locations

US (1)