Trial Outcomes & Findings for Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors (NCT NCT01628913)
NCT ID: NCT01628913
Last Updated: 2016-04-07
Results Overview
PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 12 weeks after randomization. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of all target lesions, or unequivocal progression of non-target lesions, or the appearance of new lesions.
TERMINATED
PHASE2
62 participants
up to approx. 18 months
2016-04-07
Participant Flow
Patients were assigned to one of the following 2 treatment arms in a ratio of 1:1: BEZ235 (investigational arm) or everolimus (control arm)
Participant milestones
| Measure |
BEZ235
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
|
Everolimus
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
|
|---|---|---|
|
Overall Study
STARTED
|
31
|
31
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
31
|
31
|
Reasons for withdrawal
| Measure |
BEZ235
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
|
Everolimus
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
|
|---|---|---|
|
Overall Study
Adverse Event
|
12
|
5
|
|
Overall Study
Disease Progression
|
11
|
14
|
|
Overall Study
Protocol Violation
|
1
|
0
|
|
Overall Study
Death
|
1
|
0
|
|
Overall Study
study terminated by Sponsor
|
4
|
9
|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Physician Decision
|
1
|
3
|
Baseline Characteristics
Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors
Baseline characteristics by cohort
| Measure |
BEZ235
n=31 Participants
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
|
Everolimus
n=31 Participants
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
|
Total
n=62 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.3 Years
STANDARD_DEVIATION 12.43 • n=5 Participants
|
57.8 Years
STANDARD_DEVIATION 11.85 • n=7 Participants
|
57.1 Years
STANDARD_DEVIATION 12.07 • n=5 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: up to approx. 18 monthsPopulation: Full analysis set: The Full analysis set (FAS) comprised all patients who were randomized to study treatment. According to the intent to treat principle, patient was analyzed according to the treatment and strata they had been assigned to during the randomization procedure.
PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 12 weeks after randomization. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of all target lesions, or unequivocal progression of non-target lesions, or the appearance of new lesions.
Outcome measures
| Measure |
BEZ235
n=31 Participants
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
|
Everolimus
n=31 Participants
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
|
|---|---|---|
|
Progression Free Survival (PFS)
|
8.2 Months
Interval 5.3 to
Upper Limit could not be calculated due to insufficient number of events.
|
10.8 Months
Interval 8.1 to
Upper Limit could not be calculated due to insufficient number of events.
|
SECONDARY outcome
Timeframe: up to approx. 18 monthsPopulation: Trial terminated based on the results of an interim analysis of the primary OM ( which demonstrated BEX235 not having improved PFS (progression free survival) vs everolimus).The secondary OM analyses were not conducted.
Proportion of patients with a best overall response during the study of complete response (CR) or partial response (PR), based on the investigator assessment. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for all target and non-target lesions, as well as new lesions as assessed by CT or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of all target lesions; Overall Response (OR) = CR + PR.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to approx. 30 monthsPopulation: Trial terminated based on the results of an interim analysis of the primary OM ( which demonstrated BEX235 not having improved PFS (progression free survival) vs everolimus).The secondary OM analyses were not conducted.
Time from randomization to the date of death due to any cause
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: up to approx. 18 monthsPopulation: Trial terminated based on the results of an interim analysis of the primary OM ( which demonstrated BEX235 not having improved PFS (progression free survival) vs everolimus).The secondary OM analyses were not conducted.
Time from randomization to the date of the first of the following events:death due to any cause or progressive disease, treatment discontinuation due to toxicity or treatment discontinuation due to patient preference
Outcome measures
Outcome data not reported
Adverse Events
BEZ235
Everolimus
Serious adverse events
| Measure |
BEZ235
n=31 participants at risk
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
|
Everolimus
n=31 participants at risk
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/31
|
3.2%
1/31
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/31
|
3.2%
1/31
|
|
Endocrine disorders
Adrenal insufficiency
|
3.2%
1/31
|
0.00%
0/31
|
|
Endocrine disorders
Cushing's syndrome
|
0.00%
0/31
|
3.2%
1/31
|
|
Gastrointestinal disorders
Abdominal pain
|
3.2%
1/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Abdominal wall haematoma
|
3.2%
1/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Ascites
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Diarrhoea
|
9.7%
3/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Intestinal obstruction
|
3.2%
1/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Large intestinal obstruction
|
0.00%
0/31
|
3.2%
1/31
|
|
Gastrointestinal disorders
Vomiting
|
6.5%
2/31
|
0.00%
0/31
|
|
General disorders
General physical health deterioration
|
3.2%
1/31
|
0.00%
0/31
|
|
General disorders
Oedema peripheral
|
0.00%
0/31
|
3.2%
1/31
|
|
General disorders
Pain
|
3.2%
1/31
|
0.00%
0/31
|
|
General disorders
Pyrexia
|
3.2%
1/31
|
0.00%
0/31
|
|
Hepatobiliary disorders
Cholecystitis
|
3.2%
1/31
|
0.00%
0/31
|
|
Infections and infestations
Escherichia sepsis
|
0.00%
0/31
|
3.2%
1/31
|
|
Infections and infestations
Febrile infection
|
3.2%
1/31
|
0.00%
0/31
|
|
Infections and infestations
Gastroenteritis
|
3.2%
1/31
|
0.00%
0/31
|
|
Infections and infestations
Pneumonia
|
0.00%
0/31
|
3.2%
1/31
|
|
Infections and infestations
Sepsis
|
0.00%
0/31
|
6.5%
2/31
|
|
Infections and infestations
Viral infection
|
3.2%
1/31
|
0.00%
0/31
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/31
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Hypercalcaemia
|
0.00%
0/31
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.2%
1/31
|
0.00%
0/31
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/31
|
3.2%
1/31
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
B-cell lymphoma stage III
|
3.2%
1/31
|
0.00%
0/31
|
|
Psychiatric disorders
Confusional state
|
0.00%
0/31
|
3.2%
1/31
|
|
Renal and urinary disorders
Nephritis
|
3.2%
1/31
|
0.00%
0/31
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/31
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.2%
1/31
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
3.2%
1/31
|
0.00%
0/31
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/31
|
3.2%
1/31
|
|
Vascular disorders
Embolism
|
3.2%
1/31
|
0.00%
0/31
|
|
Vascular disorders
Hypertension
|
3.2%
1/31
|
0.00%
0/31
|
|
Vascular disorders
Peripheral artery aneurysm
|
3.2%
1/31
|
0.00%
0/31
|
Other adverse events
| Measure |
BEZ235
n=31 participants at risk
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
|
Everolimus
n=31 participants at risk
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
12.9%
4/31
|
16.1%
5/31
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
3.2%
1/31
|
16.1%
5/31
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
9.7%
3/31
|
25.8%
8/31
|
|
Blood and lymphatic system disorders
Anaemia
|
25.8%
8/31
|
35.5%
11/31
|
|
Blood and lymphatic system disorders
Leukocytosis
|
6.5%
2/31
|
0.00%
0/31
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.5%
2/31
|
6.5%
2/31
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
6.5%
2/31
|
12.9%
4/31
|
|
Cardiac disorders
Palpitations
|
6.5%
2/31
|
3.2%
1/31
|
|
Gastrointestinal disorders
Abdominal distension
|
3.2%
1/31
|
9.7%
3/31
|
|
Gastrointestinal disorders
Abdominal pain
|
38.7%
12/31
|
25.8%
8/31
|
|
Gastrointestinal disorders
Abdominal pain upper
|
16.1%
5/31
|
16.1%
5/31
|
|
Gastrointestinal disorders
Cheilitis
|
0.00%
0/31
|
6.5%
2/31
|
|
Gastrointestinal disorders
Constipation
|
12.9%
4/31
|
16.1%
5/31
|
|
Gastrointestinal disorders
Diarrhoea
|
90.3%
28/31
|
54.8%
17/31
|
|
Gastrointestinal disorders
Dry mouth
|
0.00%
0/31
|
12.9%
4/31
|
|
Gastrointestinal disorders
Dyspepsia
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Dysphagia
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Flatulence
|
12.9%
4/31
|
6.5%
2/31
|
|
Gastrointestinal disorders
Haemorrhoids
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Mouth ulceration
|
0.00%
0/31
|
6.5%
2/31
|
|
Gastrointestinal disorders
Nausea
|
54.8%
17/31
|
32.3%
10/31
|
|
Gastrointestinal disorders
Oesophagitis
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Proctalgia
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Proctitis
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Rectal haemorrhage
|
6.5%
2/31
|
0.00%
0/31
|
|
Gastrointestinal disorders
Stomatitis
|
74.2%
23/31
|
64.5%
20/31
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/31
|
6.5%
2/31
|
|
Gastrointestinal disorders
Vomiting
|
45.2%
14/31
|
22.6%
7/31
|
|
General disorders
Asthenia
|
41.9%
13/31
|
41.9%
13/31
|
|
General disorders
Face oedema
|
0.00%
0/31
|
6.5%
2/31
|
|
General disorders
Fatigue
|
22.6%
7/31
|
32.3%
10/31
|
|
General disorders
Influenza like illness
|
9.7%
3/31
|
6.5%
2/31
|
|
General disorders
Mucosal inflammation
|
3.2%
1/31
|
9.7%
3/31
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/31
|
6.5%
2/31
|
|
General disorders
Oedema peripheral
|
19.4%
6/31
|
35.5%
11/31
|
|
General disorders
Pyrexia
|
29.0%
9/31
|
12.9%
4/31
|
|
General disorders
Xerosis
|
0.00%
0/31
|
9.7%
3/31
|
|
Infections and infestations
Conjunctivitis
|
3.2%
1/31
|
6.5%
2/31
|
|
Infections and infestations
Nasopharyngitis
|
6.5%
2/31
|
16.1%
5/31
|
|
Infections and infestations
Oral herpes
|
0.00%
0/31
|
6.5%
2/31
|
|
Infections and infestations
Tooth infection
|
0.00%
0/31
|
12.9%
4/31
|
|
Infections and infestations
Upper respiratory tract infection
|
9.7%
3/31
|
9.7%
3/31
|
|
Infections and infestations
Urinary tract infection
|
9.7%
3/31
|
0.00%
0/31
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/31
|
6.5%
2/31
|
|
Investigations
Alanine aminotransferase increased
|
16.1%
5/31
|
9.7%
3/31
|
|
Investigations
Aspartate aminotransferase increased
|
12.9%
4/31
|
6.5%
2/31
|
|
Investigations
Blood cholesterol increased
|
3.2%
1/31
|
12.9%
4/31
|
|
Investigations
Blood creatinine increased
|
19.4%
6/31
|
6.5%
2/31
|
|
Investigations
Cardiac murmur
|
0.00%
0/31
|
6.5%
2/31
|
|
Investigations
Gamma-glutamyltransferase increased
|
9.7%
3/31
|
0.00%
0/31
|
|
Investigations
Pancreatic enzymes decreased
|
6.5%
2/31
|
0.00%
0/31
|
|
Investigations
Platelet count decreased
|
0.00%
0/31
|
22.6%
7/31
|
|
Investigations
Weight decreased
|
12.9%
4/31
|
19.4%
6/31
|
|
Metabolism and nutrition disorders
Decreased appetite
|
29.0%
9/31
|
41.9%
13/31
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
0.00%
0/31
|
12.9%
4/31
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
29.0%
9/31
|
35.5%
11/31
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
0.00%
0/31
|
16.1%
5/31
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
3.2%
1/31
|
6.5%
2/31
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
6.5%
2/31
|
3.2%
1/31
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
3.2%
1/31
|
6.5%
2/31
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
9.7%
3/31
|
12.9%
4/31
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.9%
4/31
|
6.5%
2/31
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
6.5%
2/31
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
9.7%
3/31
|
3.2%
1/31
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.7%
3/31
|
9.7%
3/31
|
|
Musculoskeletal and connective tissue disorders
Pain in jaw
|
3.2%
1/31
|
6.5%
2/31
|
|
Nervous system disorders
Dizziness
|
0.00%
0/31
|
6.5%
2/31
|
|
Nervous system disorders
Dysgeusia
|
16.1%
5/31
|
9.7%
3/31
|
|
Nervous system disorders
Headache
|
19.4%
6/31
|
22.6%
7/31
|
|
Nervous system disorders
Lethargy
|
6.5%
2/31
|
3.2%
1/31
|
|
Nervous system disorders
Tremor
|
6.5%
2/31
|
3.2%
1/31
|
|
Psychiatric disorders
Depression
|
9.7%
3/31
|
6.5%
2/31
|
|
Psychiatric disorders
Insomnia
|
3.2%
1/31
|
9.7%
3/31
|
|
Renal and urinary disorders
Proteinuria
|
6.5%
2/31
|
0.00%
0/31
|
|
Renal and urinary disorders
Renal failure
|
6.5%
2/31
|
3.2%
1/31
|
|
Respiratory, thoracic and mediastinal disorders
Nasal inflammation
|
6.5%
2/31
|
0.00%
0/31
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/31
|
12.9%
4/31
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Acne
|
3.2%
1/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
6.5%
2/31
|
3.2%
1/31
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
0.00%
0/31
|
25.8%
8/31
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.00%
0/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Erythema
|
6.5%
2/31
|
12.9%
4/31
|
|
Skin and subcutaneous tissue disorders
Onychoclasis
|
0.00%
0/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
19.4%
6/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Rash
|
35.5%
11/31
|
41.9%
13/31
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
3.2%
1/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Rash pruritic
|
6.5%
2/31
|
0.00%
0/31
|
|
Skin and subcutaneous tissue disorders
Skin exfoliation
|
0.00%
0/31
|
6.5%
2/31
|
|
Skin and subcutaneous tissue disorders
Skin lesion
|
0.00%
0/31
|
6.5%
2/31
|
|
Vascular disorders
Hypertension
|
6.5%
2/31
|
6.5%
2/31
|
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 (ie, data from all sites) in the clinical trial.
- Publication restrictions are in place
Restriction type: OTHER