Salivary Gland DysfunctionEarly Phase 1NCT03578432

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

A Early Phase 1 study testing Everolimus, Laboratory Biomarker Analysis and Survey Administration in people with Salivary Gland Dysfunction and Xerostomia, run by University of Arizona at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Salivary Gland Dysfunction, Xerostomia, Head and Neck Cancer
What is being tested?: Everolimus, Laboratory Biomarker Analysis and Survey Administration
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 2 participants
Where: 1 siteUnited States
Study dates: 4 May 2018to 15 Nov 2019
Phase: Early Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

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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

Who cannot join

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

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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
Patients who are currently part of or have participated in any clinical investigation with an investigational drug within 1 month prior to dosing
Pregnant or nursing (lactating) women
Women of child-bearing potential (WOCBP) (including female pediatric patients who are menarcheal or who become menarcheal during the treatment), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after; women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms); highly effective contraception methods include combination of any two of the following:
Use of oral, injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example, hormone vaginal ring or transdermal hormone contraception; in case of use of oral contraception women should have been stable on the oral agent for a minimum of 3 months before taking everolimus
Total abstinence
Male partner sterilization; (the vasectomized male partner should be the sole partner for that subject)
Female sterilization have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks prior torandomization; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential
Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment

Trial locations and contacts

1 site in 1 country.

United States1 site

The University of Arizona Cancer Center
Phoenix, Arizona, 85012

Other trials in United States

About this study

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

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

Conditions: Salivary Gland Dysfunction, Xerostomia, Head and Neck Cancer
Being tested: Everolimus, Laboratory Biomarker Analysis, Survey Administration
Keywords: Xerostomia, Dry Mouth, Salivary Gland Dysfunction, Head and Neck Cancer, Mouth Cancer, Everolimus, Rapamycin, Neck Cancer, Saliva
Medical subject headings: Xerostomia, Head and Neck Neoplasms, Mouth Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

EverolimusDrug
Also called 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001
Given PO
Laboratory Biomarker AnalysisOther
Correlative studies
Survey AdministrationOther
Ancillary studies

Study groups in NCT03578432
Study group	Role	What they receive
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. Receives: Drug: Everolimus; Other: Laboratory Biomarker Analysis; Other: Survey Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: At 3 months after completion of radiation or chemoradiation therapy

Secondary outcomes (4)

Change of saliva flow rates
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.
Measured: Up to 6 months after completion of radiation or chemoradiation therapy
Saliva protein composition
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.
Measured: Up to 6 months after completion of radiation or chemoradiation therapy
Total score obtained on Xerostomia Visual Analog Scale survey
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.
Measured: Up to 6 months after completion of radiation or chemoradiation therapy
Total score obtained on Xerostomia Inventory Survey
Will be explored using graphical methods. Measures xerostomia symptoms.
Measured: Up to 6 months after completion of radiation or chemoradiation therapy

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

4 May 201815 Nov 2019

First posted6 Jul 2018
Study start4 May 2018
Primary completion15 Nov 2019
Study completion15 Nov 2019

Why it stopped: UACC-PHX is no longer able to support the study and Novartis is unable to provide drug beyond December 2019.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Salivary Gland DysfunctionStudies of the same condition, open and under way.
More trials run by University of ArizonaThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Early Phase 1
Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 2 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03578432
Sponsor's protocol ID: PHXB-17-0072-70-15
Other IDs: NCI-2018-00492, CRAD001XUA274T, PHXB-17-0072-70-15, P30CA023074
Status last verified: Nov 2019
First submitted: 15 Jun 2018
Last updated: 2 Dec 2019
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Undecided

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Evaluation of the Prevalence, and Immunological Characteristics of Small Fiber Neuropathy in Patients With Primary Sjögren's Syndrome
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Characterization of Diseases With Salivary Gland Involvement
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Exosome and Mesenchymal Stem Cell Treatment for Salivary Gland Dysfunction in Primary Sjögren Syndrome
Sjogren Syndrome, Xerostomia
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The Effect of Telerehabilitation Based Physical Activity Training Associated With Single and Dual Task Training on Physical and Cognitive Functions in Individuals With Primary Sjögren's Syndrome
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Ocular Surface Changes and Meibomian Gland Dysfunction in Rheumatologic Patients
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All Salivary Gland Dysfunction trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical Evaluation of Everolimus (a Rapamycin Analog) in Restoring Salivary Gland Function to Patients Treated With Radiotherapy for Head and Neck Cancer
ClinicalTrials.gov ID: NCT03578432
Acronym / sponsor ID: PHXB-17-0072-70-15
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
Phase: Early Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: UACC-PHX is no longer able to support the study and Novartis is unable to provide drug beyond December 2019.
Enrolment: 2 participants (actual)
Lead sponsor: University of ArizonaUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 4 May 2018 (actual)
Primary completion: 15 Nov 2019 (actual)
Study completion: 15 Nov 2019 (actual)
First posted: 6 Jul 2018 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

PRIMARY OBJECTIVES:

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:

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.

Study design

Primary purpose: Supportive care
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Supportive care (everolimus, saliva output testing)	Experimental	Drug: Everolimus, Other: Laboratory Biomarker Analysis, Other: Survey AdministrationParticipants 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.

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

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

Key exclusion criteria (23 listed)

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:

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
EverolimusAlso: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001Given PO	Drug	Supportive care (everolimus, saliva output testing)
Laboratory Biomarker AnalysisCorrelative studies	Other	Supportive care (everolimus, saliva output testing)
Survey AdministrationAncillary studies	Other	Supportive care (everolimus, saliva output testing)

Primary outcome

Percent recovery of salivary gland function
Time frame: At 3 months after completion of radiation or chemoradiation therapy
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.

4 secondary outcomes

Change of saliva flow rates
Time frame: Up to 6 months after completion of radiation or chemoradiation therapy
Saliva protein composition
Time frame: Up to 6 months after completion of radiation or chemoradiation therapy
Total score obtained on Xerostomia Visual Analog Scale survey
Time frame: Up to 6 months after completion of radiation or chemoradiation therapy
Total score obtained on Xerostomia Inventory Survey
Time frame: Up to 6 months after completion of radiation or chemoradiation therapy

Results and safety

The study was stopped early (reason given: UACC-PHX is no longer able to support the study and Novartis is unable to provide drug beyond December 2019.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2019.
Individual participant dataSharing planned: Undecided

Related trials for Salivary Gland Dysfunction

Recruiting
Evaluation of the Prevalence, and Immunological Characteristics of Small Fiber Neuropathy in Patients With Primary Sjögren's Syndrome
Sjögren's Syndrome, Small Fiber Neuropathy
RecruitingObservational study
Characterization of Diseases With Salivary Gland Involvement
Healthy Volunteer, Sjogren's Syndrome
Not yet recruitingPhase 2
Exosome and Mesenchymal Stem Cell Treatment for Salivary Gland Dysfunction in Primary Sjögren Syndrome
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Active, not recruiting
The Effect of Telerehabilitation Based Physical Activity Training Associated With Single and Dual Task Training on Physical and Cognitive Functions in Individuals With Primary Sjögren's Syndrome
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Not yet recruitingObservational study
Ocular Surface Changes and Meibomian Gland Dysfunction in Rheumatologic Patients
Meibomian Gland Dysfunction, Dry Eye Syndromes

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Panayiotis Savvides principal investigator

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

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percent recovery of salivary gland function (time frame: At 3 months after completion of radiation or chemoradiation therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03578432.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2019.