Trial Outcomes & Findings for Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer (NCT NCT00426556)
NCT ID: NCT00426556
Last Updated: 2015-12-28
Results Overview
The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
88 participants
Primary outcome timeframe
every 8 - 9 weeks until disease progression or a new lesion is identified
Results posted on
2015-12-28
Participant Flow
Based on the results of the Phase I portion of this study, in addition to all available information on daily and weekly everolimus regimen in breast cancer and other tumors, all patients in the Phase II portion of the study were allocated to one arm to receive the recommended everolimus dose of 10 mg daily in combination with PT.
Participant milestones
| Measure |
Phase I - RAD001 5mg + PT, Daily
Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 30mg + PT, Weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
|
Phase II - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Phase I - Core Phase
STARTED
|
6
|
17
|
10
|
0
|
|
Phase I - Core Phase
COMPLETED
|
5
|
7
|
7
|
0
|
|
Phase I - Core Phase
NOT COMPLETED
|
1
|
10
|
3
|
0
|
|
Phase I - Extension Phase
STARTED
|
5
|
7
|
7
|
0
|
|
Phase I - Extension Phase
COMPLETED
|
0
|
1
|
0
|
0
|
|
Phase I - Extension Phase
NOT COMPLETED
|
5
|
6
|
7
|
0
|
|
Phase II - Core Phase
STARTED
|
0
|
0
|
0
|
55
|
|
Phase II - Core Phase
COMPLETED
|
0
|
0
|
0
|
28
|
|
Phase II - Core Phase
NOT COMPLETED
|
0
|
0
|
0
|
27
|
|
Phase II - Extension Phase
STARTED
|
0
|
0
|
0
|
24
|
|
Phase II - Extension Phase
COMPLETED
|
0
|
0
|
0
|
1
|
|
Phase II - Extension Phase
NOT COMPLETED
|
0
|
0
|
0
|
23
|
Reasons for withdrawal
| Measure |
Phase I - RAD001 5mg + PT, Daily
Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 30mg + PT, Weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
|
Phase II - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Phase I - Core Phase
Disease Progression
|
0
|
6
|
2
|
0
|
|
Phase I - Core Phase
Adverse Event
|
1
|
3
|
1
|
0
|
|
Phase I - Core Phase
Death
|
0
|
1
|
0
|
0
|
|
Phase I - Extension Phase
Adverse Event
|
0
|
1
|
1
|
0
|
|
Phase I - Extension Phase
Disease Progression
|
5
|
5
|
6
|
0
|
|
Phase II - Core Phase
Withdrawal by Subject
|
0
|
0
|
0
|
3
|
|
Phase II - Core Phase
Disease Progression
|
0
|
0
|
0
|
16
|
|
Phase II - Core Phase
Adverse Event
|
0
|
0
|
0
|
8
|
|
Phase II - Extension Phase
Disease Progression
|
0
|
0
|
0
|
21
|
|
Phase II - Extension Phase
Adverse Event
|
0
|
0
|
0
|
2
|
Baseline Characteristics
Efficacy and Safety of Everolimus in Combination Therapy, in Patients With HER2-overexpressing Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Phase I - RAD001 5mg + PT, Daily
n=6 Participants
Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 10mg + PT, Daily
n=17 Participants
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 30mg + PT, Weekly
n=10 Participants
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
|
Phase II - RAD001 10mg + PT, Daily
n=55 Participants
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Total
n=88 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Customized
Phase I : < 65
|
6 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
25 Participants
n=21 Participants
|
|
Age, Customized
Phase I : >= 65
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
|
Age, Customized
Phase II : < 65
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
49 Participants
n=4 Participants
|
49 Participants
n=21 Participants
|
|
Age, Customized
Phase II : >= 65
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
|
Sex/Gender, Customized
Phase I- Female
|
6 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
33 Participants
n=21 Participants
|
|
Sex/Gender, Customized
Phase II - Female
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
55 Participants
n=4 Participants
|
55 Participants
n=21 Participants
|
|
Who Performance Status
0
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
49 Participants
n=21 Participants
|
|
Who Performance Status
1
|
2 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
19 Participants
n=4 Participants
|
39 Participants
n=21 Participants
|
PRIMARY outcome
Timeframe: every 8 - 9 weeks until disease progression or a new lesion is identifiedPopulation: The Full Analysis Set (FAS) consisted of all patients who received a least one dose of any one compound of the study treatment. Patients were analyzed according to the everolimus dose level to which they enrolled.
The primary objective of this phase II study was to evaluate the efficacy of the dose level/regimen of everolimus recommended from the Phase I with trastuzumab and paclitaxel (PT) therapy in patients with HER2-overexpressing metastatic breast cancer whose disease progressed on/after trastuzumab mono-and/or combination therapy based on the evaluation of objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST). Objective response rate (ORR) was defined as the proportion of patients with a best overall response (BOR) of complete response (CR) or partial response (PR). Only patients with measurable disease (the presence of at least one measurable lesion) at baseline were included in the study. CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters.
Outcome measures
| Measure |
Phase I - RAD001 5mg + PT, Daily
Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 30mg + PT, Weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
|
Phase II - RAD001 10mg + PT, Daily
n=55 Participants
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Phase II: Overall Response Rate
|
—
|
—
|
—
|
21.8 Percentage of Participants
|
SECONDARY outcome
Timeframe: every 8 - 9 weeks until disease progression or a new lesion is identifiedPopulation: The Full Analysis Set (FAS) consisted of all patients who received a least one dose of any one compound of the study treatment. Patients were analyzed according to the everolimus dose level to which they enrolled.
BOR was determined based on investigator assessment of overall lesion response using RECIST criteria guidelines. BOR = objective responses rate (ORR), disease control rate (DCR) or clinical benefit rate (CBR). ORR = (complete response (CR) or partial response(PR); DCR = (CR or PR or Stable disease (SD); CBR = (CR or PR or SD \>= 24 weeks).CR = Disappearance of all target lesions; PR = At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for partial disease (PD). PD = At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline.
Outcome measures
| Measure |
Phase I - RAD001 5mg + PT, Daily
n=6 Participants
Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 10mg + PT, Daily
n=17 Participants
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 30mg + PT, Weekly
n=10 Participants
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
|
Phase II - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Phase I: Best Overall Response (BOR)
Objective Response Rate (ORR)
|
83.3 Percentage of Participants
|
23.5 Percentage of Participants
|
30.0 Percentage of Participants
|
—
|
|
Phase I: Best Overall Response (BOR)
Disease Control Rate (DCR)
|
83.3 Percentage of Participants
|
82.4 Percentage of Participants
|
80.0 Percentage of Participants
|
—
|
|
Phase I: Best Overall Response (BOR)
Clinical Benefit Rate (CBR)
|
83.3 Percentage of Participants
|
47.1 Percentage of Participants
|
70.0 Percentage of Participants
|
—
|
SECONDARY outcome
Timeframe: every 8 - 9 weeks until disease progression or a new lesion is identifiedPopulation: The Full Analysis Set (FAS) consisted of all patients who received a least one dose of any one compound of the study treatment. Patients were analyzed according to the everolimus dose level to which they enrolled.
PFS is defined as the time from start of treatment to the date of first documented progression or death due to any cause. If a patient has not had an event, PFS will be censored at the date of last adequate tumor assessment.
Outcome measures
| Measure |
Phase I - RAD001 5mg + PT, Daily
Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 30mg + PT, Weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
|
Phase II - RAD001 10mg + PT, Daily
n=55 Participants
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Phase II: Progression Free Survival (PFS)
|
—
|
—
|
—
|
5.52 Months
Interval 4.99 to 7.69
|
SECONDARY outcome
Timeframe: every 3 months until deathPopulation: The Full Analysis Set (FAS) consisted of all patients who received a least one dose of any one compound of the study treatment. Patients were analyzed according to the everolimus dose level to which they enrolled.
Overall survival (OS) is defined as the time from start of treatment to the date of death due to any cause. If a patient is not known to have died, survival was censored at the last date of contact. OS was to be reported at extension and after 3-year follow-up. The Kaplan-Meier median was used to analyze the OS.
Outcome measures
| Measure |
Phase I - RAD001 5mg + PT, Daily
Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 10mg + PT, Daily
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - RAD001 30mg + PT, Weekly
Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab.
|
Phase II - RAD001 10mg + PT, Daily
n=55 Participants
Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Phase II: Overall Survival (OS)
|
—
|
—
|
—
|
18.07 Months
Interval 12.85 to 24.11
|
Adverse Events
Phase I - Everolimus 5mg Daily + PT
Serious events: 3 serious events
Other events: 6 other events
Deaths: 0 deaths
Phase I - Everolimus 10mg Daily + PT
Serious events: 6 serious events
Other events: 17 other events
Deaths: 0 deaths
Phase I - Everolimus 30mg Weekly + PT
Serious events: 7 serious events
Other events: 10 other events
Deaths: 0 deaths
Phase II - Everolimus 10mg Daily + PT
Serious events: 26 serious events
Other events: 55 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase I - Everolimus 5mg Daily + PT
n=6 participants at risk
Phase I - Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - Everolimus 10mg Daily + PT
n=17 participants at risk
Phase I - Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - Everolimus 30mg Weekly + PT
n=10 participants at risk
Phase I - Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase II - Everolimus 10mg Daily + PT
n=55 participants at risk
Phase II - Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Blood and lymphatic system disorders
Leukopenia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Blood and lymphatic system disorders
Neutropenia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Cardiac disorders
Cardiopulmonary failure
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Eye disorders
Visual impairment
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Diarrhoea
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
5.5%
3/55
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Impaired gastric emptying
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Stomatitis
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
5.5%
3/55
|
|
Gastrointestinal disorders
Subileus
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
7.3%
4/55
|
|
General disorders
Asthenia
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
General disorders
General physical health deterioration
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
General disorders
Pyrexia
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
10.9%
6/55
|
|
Hepatobiliary disorders
Bile duct stenosis
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Hepatobiliary disorders
Hepatic failure
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Hepatobiliary disorders
Jaundice
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Clostridium difficile colitis
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Device related infection
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Endocarditis
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6
|
0.00%
0/17
|
20.0%
2/10
|
3.6%
2/55
|
|
Infections and infestations
Sepsis
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Septic shock
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Skin infection
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Urinary tract infection
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
White blood cell count decreased
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Metabolism and nutrition disorders
Cell death
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Vitamin D deficiency
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Musculoskeletal and connective tissue disorders
Monarthritis
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic pain
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Nervous system disorders
Coma
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Nervous system disorders
Grand mal convulsion
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Nervous system disorders
Headache
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Nervous system disorders
Intracranial pressure increased
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Alveolitis allergic
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal obstruction extrinsic
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Angioedema
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Skin and subcutaneous tissue disorders
Skin haemorrhage
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Vascular disorders
Jugular vein thrombosis
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Vascular disorders
Lymphoedema
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Vascular disorders
Superior vena cava syndrome
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
Other adverse events
| Measure |
Phase I - Everolimus 5mg Daily + PT
n=6 participants at risk
Phase I - Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - Everolimus 10mg Daily + PT
n=17 participants at risk
Phase I - Daily dosing schedule of Everolimus 5mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase I - Everolimus 30mg Weekly + PT
n=10 participants at risk
Phase I - Weekly dosing schedule of Everolimus 30mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
Phase II - Everolimus 10mg Daily + PT
n=55 participants at risk
Phase II - Daily dosing schedule of Everolimus 10mg plus Paclitaxel plus Trastuzumab. PT = Paclitaxel \& Trastuzumab
|
|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
83.3%
5/6
|
29.4%
5/17
|
40.0%
4/10
|
34.5%
19/55
|
|
Blood and lymphatic system disorders
Anaemia macrocytic
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Blood and lymphatic system disorders
Leukopenia
|
33.3%
2/6
|
52.9%
9/17
|
20.0%
2/10
|
21.8%
12/55
|
|
Blood and lymphatic system disorders
Lymphopenia
|
33.3%
2/6
|
41.2%
7/17
|
50.0%
5/10
|
20.0%
11/55
|
|
Blood and lymphatic system disorders
Microcytosis
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Blood and lymphatic system disorders
Neutropenia
|
66.7%
4/6
|
70.6%
12/17
|
50.0%
5/10
|
36.4%
20/55
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
16.7%
1/6
|
17.6%
3/17
|
0.00%
0/10
|
16.4%
9/55
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Cardiac disorders
Palpitations
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Cardiac disorders
Tachycardia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Ear and labyrinth disorders
Ear pain
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Ear and labyrinth disorders
Vertigo
|
0.00%
0/6
|
17.6%
3/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Endocrine disorders
Hypothyroidism
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Eye disorders
Diplopia
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Eye disorders
Dry eye
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Eye disorders
Eye inflammation
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Eye disorders
Eye pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Eye disorders
Lacrimation increased
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Gastrointestinal disorders
Abdominal pain
|
50.0%
3/6
|
17.6%
3/17
|
20.0%
2/10
|
14.5%
8/55
|
|
Gastrointestinal disorders
Abdominal pain lower
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
9.1%
5/55
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
0.00%
0/6
|
17.6%
3/17
|
0.00%
0/10
|
16.4%
9/55
|
|
Gastrointestinal disorders
Ascites
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Constipation
|
33.3%
2/6
|
47.1%
8/17
|
50.0%
5/10
|
23.6%
13/55
|
|
Gastrointestinal disorders
Dental caries
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Diarrhoea
|
66.7%
4/6
|
64.7%
11/17
|
70.0%
7/10
|
54.5%
30/55
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Dyspepsia
|
50.0%
3/6
|
0.00%
0/17
|
10.0%
1/10
|
7.3%
4/55
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/6
|
5.9%
1/17
|
20.0%
2/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Gastrointestinal toxicity
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Gastrointestinal disorders
Gingival hypertrophy
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Gingival pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Gingivitis
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Nausea
|
50.0%
3/6
|
41.2%
7/17
|
50.0%
5/10
|
38.2%
21/55
|
|
Gastrointestinal disorders
Odynophagia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Oral disorder
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
5.5%
3/55
|
|
Gastrointestinal disorders
Stomatitis
|
50.0%
3/6
|
94.1%
16/17
|
80.0%
8/10
|
76.4%
42/55
|
|
Gastrointestinal disorders
Tooth loss
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Gastrointestinal disorders
Vomiting
|
33.3%
2/6
|
29.4%
5/17
|
40.0%
4/10
|
21.8%
12/55
|
|
General disorders
Adverse drug reaction
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
General disorders
Asthenia
|
66.7%
4/6
|
47.1%
8/17
|
60.0%
6/10
|
50.9%
28/55
|
|
General disorders
Chest pain
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
3.6%
2/55
|
|
General disorders
Chills
|
16.7%
1/6
|
5.9%
1/17
|
10.0%
1/10
|
3.6%
2/55
|
|
General disorders
Face oedema
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
5.5%
3/55
|
|
General disorders
Facial pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
General disorders
Fatigue
|
33.3%
2/6
|
23.5%
4/17
|
30.0%
3/10
|
21.8%
12/55
|
|
General disorders
Gait disturbance
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
0.00%
0/55
|
|
General disorders
General physical health deterioration
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
General disorders
Influenza like illness
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
General disorders
Injection site pain
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
5.5%
3/55
|
|
General disorders
Oedema
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
1.8%
1/55
|
|
General disorders
Oedema peripheral
|
33.3%
2/6
|
64.7%
11/17
|
30.0%
3/10
|
23.6%
13/55
|
|
General disorders
Pyrexia
|
66.7%
4/6
|
41.2%
7/17
|
10.0%
1/10
|
34.5%
19/55
|
|
General disorders
Xerosis
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Hepatobiliary disorders
Cytolytic hepatitis
|
33.3%
2/6
|
0.00%
0/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Hepatobiliary disorders
Hepatic steatosis
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Hepatobiliary disorders
Hepatomegaly
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Immune system disorders
Seasonal allergy
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Infections and infestations
Acute tonsillitis
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Infections and infestations
Bronchitis
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Infections and infestations
Candidiasis
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Clostridial infection
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Cystitis
|
16.7%
1/6
|
0.00%
0/17
|
20.0%
2/10
|
1.8%
1/55
|
|
Infections and infestations
Device related infection
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Ear infection
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Infections and infestations
Erysipelas
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Escherichia urinary tract infection
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Folliculitis
|
16.7%
1/6
|
23.5%
4/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Infections and infestations
Gastroenteritis
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Infections and infestations
Genital herpes
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Helicobacter infection
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Herpes simplex
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Herpes zoster
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Influenza
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Localised infection
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Infections and infestations
Lymphangitis
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Nasopharyngitis
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
18.2%
10/55
|
|
Infections and infestations
Oral herpes
|
0.00%
0/6
|
17.6%
3/17
|
0.00%
0/10
|
9.1%
5/55
|
|
Infections and infestations
Oral infection
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Pharyngitis
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Infections and infestations
Pneumonia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Rhinitis
|
50.0%
3/6
|
29.4%
5/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Sinusitis
|
16.7%
1/6
|
17.6%
3/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Infections and infestations
Skin infection
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Subcutaneous abscess
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Tonsillitis
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Tooth abscess
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Tooth infection
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Infections and infestations
Upper respiratory tract infection
|
16.7%
1/6
|
11.8%
2/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Infections and infestations
Urinary tract infection
|
16.7%
1/6
|
17.6%
3/17
|
10.0%
1/10
|
18.2%
10/55
|
|
Infections and infestations
Vaginal infection
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Viral infection
|
16.7%
1/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Infections and infestations
Vulvovaginal mycotic infection
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Infections and infestations
Wound infection
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Injury, poisoning and procedural complications
Radiation pneumonitis
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
Alanine aminotransferase increased
|
16.7%
1/6
|
11.8%
2/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Investigations
Aspartate aminotransferase increased
|
16.7%
1/6
|
23.5%
4/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Investigations
Blood creatine phosphokinase MB increased
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
Blood creatine phosphokinase increased
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
Blood creatinine increased
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Investigations
Blood magnesium decreased
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Investigations
Blood phosphorus decreased
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Investigations
Blood potassium decreased
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Investigations
Carbon monoxide diffusing capacity decreased
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Investigations
Echography abnormal
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
Ejection fraction decreased
|
16.7%
1/6
|
5.9%
1/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Investigations
Electrocardiogram abnormal
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Investigations
Haemoglobin decreased
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Investigations
Transaminases increased
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
Troponin I increased
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
Weight decreased
|
33.3%
2/6
|
17.6%
3/17
|
20.0%
2/10
|
20.0%
11/55
|
|
Investigations
Weight increased
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Investigations
White blood cell count decreased
|
0.00%
0/6
|
0.00%
0/17
|
20.0%
2/10
|
0.00%
0/55
|
|
Metabolism and nutrition disorders
Cell death
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Metabolism and nutrition disorders
Decreased appetite
|
33.3%
2/6
|
41.2%
7/17
|
30.0%
3/10
|
18.2%
10/55
|
|
Metabolism and nutrition disorders
Diabetes mellitus
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Metabolism and nutrition disorders
Electrolyte imbalance
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
5.5%
3/55
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Metabolism and nutrition disorders
Hypoalbuminaemia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
16.7%
1/6
|
11.8%
2/17
|
10.0%
1/10
|
12.7%
7/55
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
33.3%
2/6
|
35.3%
6/17
|
20.0%
2/10
|
18.2%
10/55
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
33.3%
2/6
|
17.6%
3/17
|
10.0%
1/10
|
12.7%
7/55
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Musculoskeletal and connective tissue disorders
Groin pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
0.00%
0/6
|
17.6%
3/17
|
0.00%
0/10
|
14.5%
8/55
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
16.7%
1/6
|
5.9%
1/17
|
10.0%
1/10
|
16.4%
9/55
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
66.7%
4/6
|
17.6%
3/17
|
10.0%
1/10
|
18.2%
10/55
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/6
|
17.6%
3/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Musculoskeletal and connective tissue disorders
Tendon pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ear neoplasm
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Nervous system disorders
Dizziness
|
0.00%
0/6
|
17.6%
3/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Nervous system disorders
Dysaesthesia
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Nervous system disorders
Dysgeusia
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Nervous system disorders
Headache
|
16.7%
1/6
|
47.1%
8/17
|
30.0%
3/10
|
41.8%
23/55
|
|
Nervous system disorders
Horner's syndrome
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Nervous system disorders
Hypoaesthesia
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Nervous system disorders
Hypokinesia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Nervous system disorders
Neuropathy peripheral
|
16.7%
1/6
|
11.8%
2/17
|
10.0%
1/10
|
36.4%
20/55
|
|
Nervous system disorders
Neurotoxicity
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
10.9%
6/55
|
|
Nervous system disorders
Paraesthesia
|
33.3%
2/6
|
35.3%
6/17
|
40.0%
4/10
|
10.9%
6/55
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
5.5%
3/55
|
|
Nervous system disorders
Sciatica
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Nervous system disorders
Sinus headache
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Nervous system disorders
Somnolence
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Psychiatric disorders
Agitation
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Psychiatric disorders
Confusional state
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Psychiatric disorders
Depression
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/6
|
23.5%
4/17
|
20.0%
2/10
|
10.9%
6/55
|
|
Psychiatric disorders
Mood altered
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Psychiatric disorders
Sleep disorder
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Renal and urinary disorders
Haematuria
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Renal and urinary disorders
Pollakiuria
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Renal and urinary disorders
Proteinuria
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Reproductive system and breast disorders
Breast pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Reproductive system and breast disorders
Genital discomfort
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Reproductive system and breast disorders
Vaginal haemorrhage
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
16.7%
1/6
|
35.3%
6/17
|
20.0%
2/10
|
36.4%
20/55
|
|
Respiratory, thoracic and mediastinal disorders
Dysphonia
|
0.00%
0/6
|
17.6%
3/17
|
10.0%
1/10
|
5.5%
3/55
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
33.3%
2/6
|
35.3%
6/17
|
20.0%
2/10
|
16.4%
9/55
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
50.0%
3/6
|
64.7%
11/17
|
30.0%
3/10
|
29.1%
16/55
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Larynx irritation
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
16.7%
1/6
|
5.9%
1/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Respiratory, thoracic and mediastinal disorders
Obstructive airways disorder
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
0.00%
0/6
|
11.8%
2/17
|
10.0%
1/10
|
10.9%
6/55
|
|
Respiratory, thoracic and mediastinal disorders
Pharyngeal ulceration
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
33.3%
2/6
|
5.9%
1/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Respiratory, thoracic and mediastinal disorders
Sinus congestion
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Respiratory, thoracic and mediastinal disorders
Tracheal pain
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Acne
|
16.7%
1/6
|
0.00%
0/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
66.7%
4/6
|
35.3%
6/17
|
50.0%
5/10
|
27.3%
15/55
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
0.00%
0/6
|
17.6%
3/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
50.0%
3/6
|
11.8%
2/17
|
20.0%
2/10
|
10.9%
6/55
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/6
|
11.8%
2/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Erythema
|
0.00%
0/6
|
17.6%
3/17
|
20.0%
2/10
|
18.2%
10/55
|
|
Skin and subcutaneous tissue disorders
Hyperkeratosis
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Nail disorder
|
33.3%
2/6
|
5.9%
1/17
|
0.00%
0/10
|
10.9%
6/55
|
|
Skin and subcutaneous tissue disorders
Nail toxicity
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
10.9%
6/55
|
|
Skin and subcutaneous tissue disorders
Onycholysis
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Skin and subcutaneous tissue disorders
Onychomadesis
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
1.8%
1/55
|
|
Skin and subcutaneous tissue disorders
Palmar-plantar erythrodysaesthesia syndrome
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Skin and subcutaneous tissue disorders
Pigmentation disorder
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/6
|
5.9%
1/17
|
20.0%
2/10
|
9.1%
5/55
|
|
Skin and subcutaneous tissue disorders
Purpura
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
1.8%
1/55
|
|
Skin and subcutaneous tissue disorders
Rash
|
33.3%
2/6
|
47.1%
8/17
|
30.0%
3/10
|
47.3%
26/55
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Rash vesicular
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Skin irritation
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Skin mass
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Skin toxicity
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
7.3%
4/55
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/6
|
0.00%
0/17
|
0.00%
0/10
|
5.5%
3/55
|
|
Vascular disorders
Arterial thrombosis limb
|
0.00%
0/6
|
0.00%
0/17
|
10.0%
1/10
|
0.00%
0/55
|
|
Vascular disorders
Hot flush
|
0.00%
0/6
|
5.9%
1/17
|
0.00%
0/10
|
3.6%
2/55
|
|
Vascular disorders
Hypertension
|
0.00%
0/6
|
5.9%
1/17
|
10.0%
1/10
|
3.6%
2/55
|
|
Vascular disorders
Lymphoedema
|
16.7%
1/6
|
17.6%
3/17
|
10.0%
1/10
|
9.1%
5/55
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Principal Investigators are NOT employed by the organization sponsoring the study. Other disclosure agreement that restricts the right of the PI 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 pooled data (i.e.,data from all sites) in clinical trial.
- Publication restrictions are in place
Restriction type: OTHER