Trial Outcomes & Findings for 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 (NCT NCT02069093)
NCT ID: NCT02069093
Last Updated: 2017-02-13
Results Overview
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.
COMPLETED
PHASE2
92 participants
56 days
2017-02-13
Participant Flow
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.
Participant milestones
| Measure |
Dexamethasone Based Mouthwash
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 Study
STARTED
|
86
|
|
Overall Study
Pharmacokinetic Analysis Set
|
50
|
|
Overall Study
COMPLETED
|
56
|
|
Overall Study
NOT COMPLETED
|
30
|
Reasons for withdrawal
| Measure |
Dexamethasone Based Mouthwash
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.
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|---|---|
|
Overall Study
Disease progression
|
14
|
|
Overall Study
New cancer therapy
|
1
|
|
Overall Study
Death
|
1
|
|
Overall Study
Administrative problems
|
1
|
|
Overall Study
Withdrawal by Subject
|
2
|
|
Overall Study
Abnormal laboratory values
|
1
|
|
Overall Study
Adverse Event
|
10
|
Baseline Characteristics
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
Baseline characteristics by cohort
| Measure |
Dexamethasone Based Mouthwash
n=86 Participants
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.
|
|---|---|
|
Age, Continuous
|
61.02 Years
STANDARD_DEVIATION 10.921 • n=99 Participants
|
|
Sex/Gender, Customized
Female
|
86 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: 56 daysPopulation: 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).
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.
Outcome measures
| Measure |
Dexamethasone Based Mouthwash
n=86 Participants
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.
|
|---|---|
|
Number of Participants With Stomatitis Grade ≥ 2
Stomatitis grade >=2: Yes
|
2 Participants
|
|
Number of Participants With Stomatitis Grade ≥ 2
Stomatitis grade >=2: No
|
83 Participants
|
|
Number of Participants With Stomatitis Grade ≥ 2
Stomatitis grade >=2: Not evaluable
|
1 Participants
|
SECONDARY outcome
Timeframe: 56 daysPopulation: 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).
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.
Outcome measures
| Measure |
Dexamethasone Based Mouthwash
n=86 Participants
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.
|
|---|---|
|
Time to Resolution of Stomatitis From Grade 2 or Greater to Grade 1 or Less
|
NA Days
Median could not be calculated due to insufficient number of participants with events.
|
SECONDARY outcome
Timeframe: 56 daysPopulation: 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).
The median number of mouthwashes per day was assessed.
Outcome measures
| Measure |
Dexamethasone Based Mouthwash
n=86 Participants
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.
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|---|---|
|
Median Number of Mouthwashes Per Day
|
3.95 Number of mouthwashes
Interval 1.9 to 4.0
|
SECONDARY outcome
Timeframe: 56 daysPopulation: 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.
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.
Outcome measures
| Measure |
Dexamethasone Based Mouthwash
n=86 Participants
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.
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|---|---|
|
Number of Participants With All Grades of Stomatitis
Stomatitis all grade
|
18 Participants
|
|
Number of Participants With All Grades of Stomatitis
Not evaluable
|
1 Participants
|
SECONDARY outcome
Timeframe: 56 daysPopulation: 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).
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.
Outcome measures
| Measure |
Dexamethasone Based Mouthwash
n=86 Participants
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.
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|---|---|
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Dose Intensity of Everolimus and Exemestane
Exemestane
|
25.0 mg/day
Interval 8.0 to 25.0
|
|
Dose Intensity of Everolimus and Exemestane
Everolimus
|
10.0 mg/day
Interval 3.0 to 10.0
|
SECONDARY outcome
Timeframe: 28 days (pre-dose)Population: 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.
Blood samples were collected and analyzed.
Outcome measures
| Measure |
Dexamethasone Based Mouthwash
n=50 Participants
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.
|
|---|---|
|
Blood Concentration of Everolimus and Exemestane
Everolimus (n=42)
|
12.047 ng/mL
Geometric Coefficient of Variation 56.492
|
|
Blood Concentration of Everolimus and Exemestane
Exemestane (n=48)
|
0.657 ng/mL
Geometric Coefficient of Variation 234.578
|
Adverse Events
Dexamethasone Based Mouthwash
Serious adverse events
| Measure |
Dexamethasone Based Mouthwash
n=92 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
1.1%
1/92
|
|
Cardiac disorders
Cardiac failure
|
1.1%
1/92
|
|
Cardiac disorders
Pericardial effusion
|
1.1%
1/92
|
|
Gastrointestinal disorders
Gastric ulcer
|
1.1%
1/92
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
1.1%
1/92
|
|
General disorders
Chest pain
|
1.1%
1/92
|
|
General disorders
Generalised oedema
|
1.1%
1/92
|
|
General disorders
Mass
|
1.1%
1/92
|
|
General disorders
Pyrexia
|
2.2%
2/92
|
|
Infections and infestations
Lung infection
|
1.1%
1/92
|
|
Infections and infestations
Pneumonia
|
2.2%
2/92
|
|
Infections and infestations
Sepsis
|
1.1%
1/92
|
|
Infections and infestations
Subcutaneous abscess
|
1.1%
1/92
|
|
Injury, poisoning and procedural complications
Femur fracture
|
1.1%
1/92
|
|
Metabolism and nutrition disorders
Dehydration
|
1.1%
1/92
|
|
Metabolism and nutrition disorders
Electrolyte depletion
|
1.1%
1/92
|
|
Metabolism and nutrition disorders
Lactic acidosis
|
1.1%
1/92
|
|
Metabolism and nutrition disorders
Metabolic acidosis
|
1.1%
1/92
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.1%
1/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Invasive lobular breast carcinoma
|
1.1%
1/92
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
1.1%
1/92
|
|
Nervous system disorders
Depressed level of consciousness
|
1.1%
1/92
|
|
Nervous system disorders
Seizure
|
1.1%
1/92
|
|
Psychiatric disorders
Agitation
|
1.1%
1/92
|
|
Psychiatric disorders
Substance abuse
|
1.1%
1/92
|
|
Renal and urinary disorders
Acute kidney injury
|
2.2%
2/92
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.3%
3/92
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
1.1%
1/92
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
1.1%
1/92
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
1.1%
1/92
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
1.1%
1/92
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
2.2%
2/92
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.1%
1/92
|
|
Vascular disorders
Deep vein thrombosis
|
1.1%
1/92
|
Other adverse events
| Measure |
Dexamethasone Based Mouthwash
n=92 participants at risk
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.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
5.4%
5/92
|
|
Gastrointestinal disorders
Diarrhoea
|
10.9%
10/92
|
|
Gastrointestinal disorders
Nausea
|
15.2%
14/92
|
|
Gastrointestinal disorders
Oral pain
|
6.5%
6/92
|
|
Gastrointestinal disorders
Stomatitis
|
27.2%
25/92
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
6/92
|
|
General disorders
Fatigue
|
17.4%
16/92
|
|
General disorders
Oedema peripheral
|
5.4%
5/92
|
|
General disorders
Pyrexia
|
7.6%
7/92
|
|
Infections and infestations
Urinary tract infection
|
8.7%
8/92
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
5.4%
5/92
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
15.2%
14/92
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
5.4%
5/92
|
|
Nervous system disorders
Dysgeusia
|
13.0%
12/92
|
|
Nervous system disorders
Headache
|
10.9%
10/92
|
|
Psychiatric disorders
Insomnia
|
9.8%
9/92
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
10.9%
10/92
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
12.0%
11/92
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
6.5%
6/92
|
|
Skin and subcutaneous tissue disorders
Rash
|
8.7%
8/92
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER