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Open-label, Phase II Study of Stomatitis Prevention With a Steroid-based Mouthwash in Post-menopausal Women With Estrogen-receptor-positive (ER+), Human Epidermal Growth Factor Receptor 2 (HER2)- Metastatic or Locally Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT02069093
Recruitment Status : Completed
First Posted : February 21, 2014
Results First Posted : February 13, 2017
Last Update Posted : February 13, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Advanced Breast Cancer
Interventions Drug: Dexamethasone based mouthwash
Drug: Everolimus
Drug: Exemestane
Enrollment 92
Recruitment Details  
Pre-assignment Details A total of 92 participants were enrolled into the study and received study treatments of everolimus and exemestane. Of these, 86 participants were confirmed to have also received the investigational treatment of dexamethasone steroid mouthwash and comprised the full analysis set (FAS). The patient disposition is based on the FAS.
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Period Title: Overall Study
Started 86
Pharmacokinetic Analysis Set 50
Completed 56
Not Completed 30
Reason Not Completed
Disease progression             14
New cancer therapy             1
Death             1
Administrative problems             1
Withdrawal by Subject             2
Abnormal laboratory values             1
Adverse Event             10
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Baseline Participants 86
Hide Baseline Analysis Population Description
Full analysis set: The full analysis set consisted of all participants who received at least one dose of study treatment (everolimus and/or exemestane) and at least one dose of investigational treatment (dexamethasone mouth wash).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 86 participants
61.02  (10.921)
Sex/Gender, Customized  
Measure Type: Number
Unit of measure:  Participants
Female Number Analyzed 86 participants
86
1.Primary Outcome
Title Number of Participants With Stomatitis Grade ≥ 2
Hide Description The incidence of grade ≥ 2 stomatitis was reported. Grade 1 = minimal symptoms, normal diet; grade 2 = symptomatic, but able to swallow a modified diet; grade 3 = symptomatic and unable to aliment or hydrate orally; and grade 4 = symptoms associated with life-threatening consequences.
Time Frame 56 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): The FAS consisted of all participants who received at least one dose of study treatment (everolimus and/or exemestane) and at least one dose of investigational treatment (dexamethasone mouth wash).
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description:
Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Participants Analyzed 86
Measure Type: Number
Unit of Measure: Participants
Stomatitis grade >=2: Yes 2
Stomatitis grade >=2: No 83
Stomatitis grade >=2: Not evaluable 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Dexamethasone Based Mouthwash
Comments A test of the incidence rate R was performed with null hypothesis H0: R>= 0.33 and alternative hypothesis Ha: R<0.33 with a one-sided significance level of 0.05. If the test statistic was negative (actual incidence rate was <0.33), the one-sided p-value for the null hypothesis R>=0.33 was presented. The null hypothesis was rejected if the statistic was negative and the corresponding p-value for the one-sided test was <0.5.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Incidence rate R
Comments [Not Specified]
2.Secondary Outcome
Title Time to Resolution of Stomatitis From Grade 2 or Greater to Grade 1 or Less
Hide Description The number of days to achieve resolution of stomatitis from grade 2 or greater to grade 1 or less was assessed. Grade 1 = minimal symptoms, normal diet; grade 2 = symptomatic, but able to swallow a modified diet; grade 3 = symptomatic and unable to aliment or hydrate orally; and grade 4 = symptoms associated with life-threatening consequences.
Time Frame 56 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: The FAS consisted of all participants who received at least one dose of study treatment (everolimus and/or exemestane) and at least one dose of investigational treatment (dexamethasone mouth wash).
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description:
Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Participants Analyzed 86
Median (Full Range)
Unit of Measure: Days
NA [1] 
(NA to NA)
[1]
Median could not be calculated due to insufficient number of participants with events.
3.Secondary Outcome
Title Median Number of Mouthwashes Per Day
Hide Description The median number of mouthwashes per day was assessed.
Time Frame 56 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: The FAS set consisted of all participants who received at least one dose of study treatment (everolimus and/or exemestane) and at least one dose of investigational treatment (dexamethasone mouth wash).
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description:
Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Participants Analyzed 86
Median (Full Range)
Unit of Measure: Number of mouthwashes
3.95
(1.9 to 4.0)
4.Secondary Outcome
Title Number of Participants With All Grades of Stomatitis
Hide Description The number of participants with all grades of stomatitis was defined as the number of participants who had stomatitis grade 1 or higher. Grade 1 = minimal symptoms, normal diet; grade 2 = symptomatic, but able to swallow a modified diet; grade 3 = symptomatic and unable to aliment or hydrate orally; and grade 4 = symptoms associated with life-threatening consequences.
Time Frame 56 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The FAS, consisting of all participants who received at least one dose of study treatment (everolimus and/or exemestane) and at least one dose of investigational treatment (dexamethasone mouth wash), was considered for the analysis. However, only those participants, who were evaluable for stomatitis grade, were analyzed.
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description:
Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Participants Analyzed 86
Measure Type: Number
Unit of Measure: Participants
Stomatitis all grade 18
Not evaluable 1
5.Secondary Outcome
Title Dose Intensity of Everolimus and Exemestane
Hide Description The dose intensity was calculated as the cumulative dose of everolimus or exemestane divided by the length of time on treatment during the first 56 days of treatment.
Time Frame 56 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
FAS: The FAS consisted of all participants who received at least one dose of study treatment (everolimus and/or exemestane) and at least one dose of investigational treatment (dexamethasone mouth wash).
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description:
Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Participants Analyzed 86
Median (Full Range)
Unit of Measure: mg/day
Everolimus
10.0
(3 to 10)
Exemestane
25.0
(8 to 25)
6.Secondary Outcome
Title Blood Concentration of Everolimus and Exemestane
Hide Description Blood samples were collected and analyzed.
Time Frame 28 days (pre-dose)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
The PK analysis set, which was a subset of the FAS, was considered for the analysis. However, only participants who had evaluable data were analyzed.
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description:
Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
Overall Number of Participants Analyzed 50
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Everolimus (n=42)
12.047
(56.492%)
Exemestane (n=48)
0.657
(234.578%)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Dexamethasone Based Mouthwash
Hide Arm/Group Description Participants swished and spat 10mL of 0.5mg/5mL dexamethasone steroid mouthwash (investigational treatment) 4 times daily (qid) orally for 2 minutes each for 8 weeks. Participants remained without food or drink (NPO) for one hour after administration of the mouthwash. Also, participants received everolimus 10 mg and exemstane 25 mg (study treatments) according to local regulations.
All-Cause Mortality
Dexamethasone Based Mouthwash
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Dexamethasone Based Mouthwash
Affected / at Risk (%)
Total   20/92 (21.74%) 
Blood and lymphatic system disorders   
Lymphadenopathy  1  1/92 (1.09%) 
Cardiac disorders   
Cardiac failure  1  1/92 (1.09%) 
Pericardial effusion  1  1/92 (1.09%) 
Gastrointestinal disorders   
Gastric ulcer  1  1/92 (1.09%) 
Rectal haemorrhage  1  1/92 (1.09%) 
General disorders   
Chest pain  1  1/92 (1.09%) 
Generalised oedema  1  1/92 (1.09%) 
Mass  1  1/92 (1.09%) 
Pyrexia  1  2/92 (2.17%) 
Infections and infestations   
Lung infection  1  1/92 (1.09%) 
Pneumonia  1  2/92 (2.17%) 
Sepsis  1  1/92 (1.09%) 
Subcutaneous abscess  1  1/92 (1.09%) 
Injury, poisoning and procedural complications   
Femur fracture  1  1/92 (1.09%) 
Metabolism and nutrition disorders   
Dehydration  1  1/92 (1.09%) 
Electrolyte depletion  1  1/92 (1.09%) 
Lactic acidosis  1  1/92 (1.09%) 
Metabolic acidosis  1  1/92 (1.09%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  1/92 (1.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Invasive lobular breast carcinoma  1  1/92 (1.09%) 
Metastases to liver  1  1/92 (1.09%) 
Nervous system disorders   
Depressed level of consciousness  1  1/92 (1.09%) 
Seizure  1  1/92 (1.09%) 
Psychiatric disorders   
Agitation  1  1/92 (1.09%) 
Substance abuse  1  1/92 (1.09%) 
Renal and urinary disorders   
Acute kidney injury  1  2/92 (2.17%) 
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  3/92 (3.26%) 
Epistaxis  1  1/92 (1.09%) 
Hypoxia  1  1/92 (1.09%) 
Pleural effusion  1  1/92 (1.09%) 
Pulmonary embolism  1  1/92 (1.09%) 
Respiratory failure  1  2/92 (2.17%) 
Skin and subcutaneous tissue disorders   
Rash  1  1/92 (1.09%) 
Vascular disorders   
Deep vein thrombosis  1  1/92 (1.09%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Dexamethasone Based Mouthwash
Affected / at Risk (%)
Total   72/92 (78.26%) 
Blood and lymphatic system disorders   
Anaemia  1  5/92 (5.43%) 
Gastrointestinal disorders   
Diarrhoea  1  10/92 (10.87%) 
Nausea  1  14/92 (15.22%) 
Oral pain  1  6/92 (6.52%) 
Stomatitis  1  25/92 (27.17%) 
Vomiting  1  6/92 (6.52%) 
General disorders   
Fatigue  1  16/92 (17.39%) 
Oedema peripheral  1  5/92 (5.43%) 
Pyrexia  1  7/92 (7.61%) 
Infections and infestations   
Urinary tract infection  1  8/92 (8.70%) 
Metabolism and nutrition disorders   
Hypercholesterolaemia  1  5/92 (5.43%) 
Hyperglycaemia  1  14/92 (15.22%) 
Hypokalaemia  1  5/92 (5.43%) 
Nervous system disorders   
Dysgeusia  1  12/92 (13.04%) 
Headache  1  10/92 (10.87%) 
Psychiatric disorders   
Insomnia  1  9/92 (9.78%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  10/92 (10.87%) 
Dyspnoea  1  11/92 (11.96%) 
Oropharyngeal pain  1  6/92 (6.52%) 
Skin and subcutaneous tissue disorders   
Rash  1  8/92 (8.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02069093     History of Changes
Other Study ID Numbers: CRAD001JUS226
First Submitted: February 20, 2014
First Posted: February 21, 2014
Results First Submitted: October 19, 2016
Results First Posted: February 13, 2017
Last Update Posted: February 13, 2017