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Trial record 15 of 128 for:    "Pancreatic Neuroendocrine Tumor"

Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors

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ClinicalTrials.gov Identifier: NCT01628913
Recruitment Status : Terminated (This trial was terminated based on an interim analysis as BEZ235 did not demonstrate a progression free survival advantage to everolimus treatment.)
First Posted : June 27, 2012
Results First Posted : April 7, 2016
Last Update Posted : April 7, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pancreatic Neuroendocrine Tumors (pNET)
Interventions Drug: BEZ235
Drug: Everolimus
Enrollment 62
Recruitment Details  
Pre-assignment Details Patients were assigned to one of the following 2 treatment arms in a ratio of 1:1: BEZ235 (investigational arm) or everolimus (control arm)
Arm/Group Title BEZ235 Everolimus
Hide Arm/Group Description Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily) Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
Period Title: Overall Study
Started 31 31
Completed 0 0
Not Completed 31 31
Reason Not Completed
Adverse Event             12             5
Disease Progression             11             14
Protocol Violation             1             0
Death             1             0
study terminated by Sponsor             4             9
Withdrawal by Subject             1             0
Physician Decision             1             3
Arm/Group Title BEZ235 Everolimus Total
Hide Arm/Group Description Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily) Patients received Everolimus 10 mg qd p.o. (by mouth, daily) Total of all reporting groups
Overall Number of Baseline Participants 31 31 62
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 31 participants 62 participants
56.3  (12.43) 57.8  (11.85) 57.1  (12.07)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 31 participants 62 participants
Female
14
  45.2%
16
  51.6%
30
  48.4%
Male
17
  54.8%
15
  48.4%
32
  51.6%
1.Primary Outcome
Title Progression Free Survival (PFS)
Hide Description 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.
Time Frame up to approx. 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title BEZ235 Everolimus
Hide Arm/Group Description:
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
Overall Number of Participants Analyzed 31 31
Median (95% Confidence Interval)
Unit of Measure: Months
8.2 [1] 
(5.3 to NA)
10.8 [1] 
(8.1 to NA)
[1]
Upper Limit could not be calculated due to insufficient number of events.
2.Secondary Outcome
Title Objective Response Rate
Hide Description 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.
Time Frame up to approx. 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title BEZ235 Everolimus
Hide Arm/Group Description:
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
3.Secondary Outcome
Title Overall Survival (OS)
Hide Description Time from randomization to the date of death due to any cause
Time Frame up to approx. 30 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title BEZ235 Everolimus
Hide Arm/Group Description:
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
4.Secondary Outcome
Title Time to Treatment Failure (TTF)
Hide Description 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
Time Frame up to approx. 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title BEZ235 Everolimus
Hide Arm/Group Description:
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title BEZ235 Everolimus
Hide Arm/Group Description Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily) Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
All-Cause Mortality
BEZ235 Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
BEZ235 Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   11/31 (35.48%)   9/31 (29.03%) 
Blood and lymphatic system disorders     
Thrombocytopenia  1  0/31 (0.00%)  1/31 (3.23%) 
Cardiac disorders     
Cardiac failure congestive  1  0/31 (0.00%)  1/31 (3.23%) 
Endocrine disorders     
Adrenal insufficiency  1  1/31 (3.23%)  0/31 (0.00%) 
Cushing's syndrome  1  0/31 (0.00%)  1/31 (3.23%) 
Gastrointestinal disorders     
Abdominal pain  1  1/31 (3.23%)  0/31 (0.00%) 
Abdominal wall haematoma  1  1/31 (3.23%)  0/31 (0.00%) 
Ascites  1  2/31 (6.45%)  0/31 (0.00%) 
Diarrhoea  1  3/31 (9.68%)  0/31 (0.00%) 
Intestinal obstruction  1  1/31 (3.23%)  0/31 (0.00%) 
Large intestinal obstruction  1  0/31 (0.00%)  1/31 (3.23%) 
Vomiting  1  2/31 (6.45%)  0/31 (0.00%) 
General disorders     
General physical health deterioration  1  1/31 (3.23%)  0/31 (0.00%) 
Oedema peripheral  1  0/31 (0.00%)  1/31 (3.23%) 
Pain  1  1/31 (3.23%)  0/31 (0.00%) 
Pyrexia  1  1/31 (3.23%)  0/31 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  1/31 (3.23%)  0/31 (0.00%) 
Infections and infestations     
Escherichia sepsis  1  0/31 (0.00%)  1/31 (3.23%) 
Febrile infection  1  1/31 (3.23%)  0/31 (0.00%) 
Gastroenteritis  1  1/31 (3.23%)  0/31 (0.00%) 
Pneumonia  1  0/31 (0.00%)  1/31 (3.23%) 
Sepsis  1  0/31 (0.00%)  2/31 (6.45%) 
Viral infection  1  1/31 (3.23%)  0/31 (0.00%) 
Injury, poisoning and procedural complications     
Femur fracture  1  0/31 (0.00%)  1/31 (3.23%) 
Metabolism and nutrition disorders     
Hypercalcaemia  1  0/31 (0.00%)  1/31 (3.23%) 
Hyperglycaemia  1  1/31 (3.23%)  0/31 (0.00%) 
Hypokalaemia  1  0/31 (0.00%)  1/31 (3.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
B-cell lymphoma stage III  1  1/31 (3.23%)  0/31 (0.00%) 
Psychiatric disorders     
Confusional state  1  0/31 (0.00%)  1/31 (3.23%) 
Renal and urinary disorders     
Nephritis  1  1/31 (3.23%)  0/31 (0.00%) 
Renal failure  1  0/31 (0.00%)  1/31 (3.23%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  1/31 (3.23%)  1/31 (3.23%) 
Pleural effusion  1  1/31 (3.23%)  0/31 (0.00%) 
Pneumonitis  1  0/31 (0.00%)  1/31 (3.23%) 
Vascular disorders     
Embolism  1  1/31 (3.23%)  0/31 (0.00%) 
Hypertension  1  1/31 (3.23%)  0/31 (0.00%) 
Peripheral artery aneurysm  1  1/31 (3.23%)  0/31 (0.00%) 
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%
BEZ235 Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   31/31 (100.00%)   30/31 (96.77%) 
Blood and lymphatic system disorders     
Anaemia  1  8/31 (25.81%)  11/31 (35.48%) 
Leukocytosis  1  2/31 (6.45%)  0/31 (0.00%) 
Neutropenia  1  2/31 (6.45%)  2/31 (6.45%) 
Thrombocytopenia  1  2/31 (6.45%)  4/31 (12.90%) 
Cardiac disorders     
Palpitations  1  2/31 (6.45%)  1/31 (3.23%) 
Gastrointestinal disorders     
Abdominal distension  1  1/31 (3.23%)  3/31 (9.68%) 
Abdominal pain  1  12/31 (38.71%)  8/31 (25.81%) 
Abdominal pain upper  1  5/31 (16.13%)  5/31 (16.13%) 
Cheilitis  1  0/31 (0.00%)  2/31 (6.45%) 
Constipation  1  4/31 (12.90%)  5/31 (16.13%) 
Diarrhoea  1  28/31 (90.32%)  17/31 (54.84%) 
Dry mouth  1  0/31 (0.00%)  4/31 (12.90%) 
Dyspepsia  1  2/31 (6.45%)  0/31 (0.00%) 
Dysphagia  1  2/31 (6.45%)  0/31 (0.00%) 
Flatulence  1  4/31 (12.90%)  2/31 (6.45%) 
Haemorrhoids  1  2/31 (6.45%)  0/31 (0.00%) 
Mouth ulceration  1  0/31 (0.00%)  2/31 (6.45%) 
Nausea  1  17/31 (54.84%)  10/31 (32.26%) 
Oesophagitis  1  2/31 (6.45%)  0/31 (0.00%) 
Proctalgia  1  2/31 (6.45%)  0/31 (0.00%) 
Proctitis  1  2/31 (6.45%)  0/31 (0.00%) 
Rectal haemorrhage  1  2/31 (6.45%)  0/31 (0.00%) 
Stomatitis  1  23/31 (74.19%)  20/31 (64.52%) 
Toothache  1  0/31 (0.00%)  2/31 (6.45%) 
Vomiting  1  14/31 (45.16%)  7/31 (22.58%) 
General disorders     
Asthenia  1  13/31 (41.94%)  13/31 (41.94%) 
Face oedema  1  0/31 (0.00%)  2/31 (6.45%) 
Fatigue  1  7/31 (22.58%)  10/31 (32.26%) 
Influenza like illness  1  3/31 (9.68%)  2/31 (6.45%) 
Mucosal inflammation  1  1/31 (3.23%)  3/31 (9.68%) 
Non-cardiac chest pain  1  0/31 (0.00%)  2/31 (6.45%) 
Oedema peripheral  1  6/31 (19.35%)  11/31 (35.48%) 
Pyrexia  1  9/31 (29.03%)  4/31 (12.90%) 
Xerosis  1  0/31 (0.00%)  3/31 (9.68%) 
Infections and infestations     
Conjunctivitis  1  1/31 (3.23%)  2/31 (6.45%) 
Nasopharyngitis  1  2/31 (6.45%)  5/31 (16.13%) 
Oral herpes  1  0/31 (0.00%)  2/31 (6.45%) 
Tooth infection  1  0/31 (0.00%)  4/31 (12.90%) 
Upper respiratory tract infection  1  3/31 (9.68%)  3/31 (9.68%) 
Urinary tract infection  1  3/31 (9.68%)  0/31 (0.00%) 
Injury, poisoning and procedural complications     
Contusion  1  0/31 (0.00%)  2/31 (6.45%) 
Investigations     
Alanine aminotransferase increased  1  5/31 (16.13%)  3/31 (9.68%) 
Aspartate aminotransferase increased  1  4/31 (12.90%)  2/31 (6.45%) 
Blood cholesterol increased  1  1/31 (3.23%)  4/31 (12.90%) 
Blood creatinine increased  1  6/31 (19.35%)  2/31 (6.45%) 
Cardiac murmur  1  0/31 (0.00%)  2/31 (6.45%) 
Gamma-glutamyltransferase increased  1  3/31 (9.68%)  0/31 (0.00%) 
Pancreatic enzymes decreased  1  2/31 (6.45%)  0/31 (0.00%) 
Platelet count decreased  1  0/31 (0.00%)  7/31 (22.58%) 
Weight decreased  1  4/31 (12.90%)  6/31 (19.35%) 
Metabolism and nutrition disorders     
Decreased appetite  1  9/31 (29.03%)  13/31 (41.94%) 
Hypercholesterolaemia  1  0/31 (0.00%)  4/31 (12.90%) 
Hyperglycaemia  1  9/31 (29.03%)  11/31 (35.48%) 
Hypertriglyceridaemia  1  0/31 (0.00%)  5/31 (16.13%) 
Hypokalaemia  1  1/31 (3.23%)  2/31 (6.45%) 
Hyponatraemia  1  2/31 (6.45%)  1/31 (3.23%) 
Hypophosphataemia  1  1/31 (3.23%)  2/31 (6.45%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  3/31 (9.68%)  4/31 (12.90%) 
Back pain  1  4/31 (12.90%)  2/31 (6.45%) 
Musculoskeletal pain  1  2/31 (6.45%)  1/31 (3.23%) 
Myalgia  1  3/31 (9.68%)  1/31 (3.23%) 
Pain in extremity  1  3/31 (9.68%)  3/31 (9.68%) 
Pain in jaw  1  1/31 (3.23%)  2/31 (6.45%) 
Nervous system disorders     
Dizziness  1  0/31 (0.00%)  2/31 (6.45%) 
Dysgeusia  1  5/31 (16.13%)  3/31 (9.68%) 
Headache  1  6/31 (19.35%)  7/31 (22.58%) 
Lethargy  1  2/31 (6.45%)  1/31 (3.23%) 
Tremor  1  2/31 (6.45%)  1/31 (3.23%) 
Psychiatric disorders     
Depression  1  3/31 (9.68%)  2/31 (6.45%) 
Insomnia  1  1/31 (3.23%)  3/31 (9.68%) 
Renal and urinary disorders     
Proteinuria  1  2/31 (6.45%)  0/31 (0.00%) 
Renal failure  1  2/31 (6.45%)  1/31 (3.23%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  3/31 (9.68%)  8/31 (25.81%) 
Dyspnoea  1  1/31 (3.23%)  5/31 (16.13%) 
Epistaxis  1  4/31 (12.90%)  5/31 (16.13%) 
Nasal inflammation  1  2/31 (6.45%)  0/31 (0.00%) 
Pneumonitis  1  0/31 (0.00%)  4/31 (12.90%) 
Productive cough  1  0/31 (0.00%)  2/31 (6.45%) 
Skin and subcutaneous tissue disorders     
Acne  1  1/31 (3.23%)  2/31 (6.45%) 
Alopecia  1  2/31 (6.45%)  1/31 (3.23%) 
Dry skin  1  0/31 (0.00%)  8/31 (25.81%) 
Eczema  1  0/31 (0.00%)  2/31 (6.45%) 
Erythema  1  2/31 (6.45%)  4/31 (12.90%) 
Onychoclasis  1  0/31 (0.00%)  2/31 (6.45%) 
Pruritus  1  6/31 (19.35%)  2/31 (6.45%) 
Rash  1  11/31 (35.48%)  13/31 (41.94%) 
Rash maculo-papular  1  1/31 (3.23%)  2/31 (6.45%) 
Rash pruritic  1  2/31 (6.45%)  0/31 (0.00%) 
Skin exfoliation  1  0/31 (0.00%)  2/31 (6.45%) 
Skin lesion  1  0/31 (0.00%)  2/31 (6.45%) 
Vascular disorders     
Hypertension  1  2/31 (6.45%)  2/31 (6.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Trial terminated based on the results of a pre-planned 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
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 (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01628913     History of Changes
Other Study ID Numbers: CBEZ235Z2401
CBEZ235Z2401 ( Other Identifier: Novartis )
2012-000769-19
First Submitted: June 25, 2012
First Posted: June 27, 2012
Results First Submitted: August 19, 2015
Results First Posted: April 7, 2016
Last Update Posted: April 7, 2016