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Efficacy of Everolimus Alone or in Combination With Pasireotide LAR in Advanced PNET (COOPERATE-2)

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ClinicalTrials.gov Identifier: NCT01374451
Recruitment Status : Terminated (The study was stopped for not meeting the primary endpoint for PFS.)
First Posted : June 16, 2011
Results First Posted : December 20, 2016
Last Update Posted : December 20, 2016
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Islet Cell Tumor
Interventions Drug: Everolimus
Drug: Pasireotide LAR
Enrollment 160
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im everolimus 10 mg once daily po alone
Period Title: Overall Study
Started 79 81
Completed 78 81
Not Completed 1 0
Reason Not Completed
Administrative problems             1             0
Arm/Group Title Paseriotide LAR + Everolimus Everolimus Total
Hide Arm/Group Description everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im everolimus 10 mg once daily po alone Total of all reporting groups
Overall Number of Baseline Participants 79 81 160
Hide Baseline Analysis Population Description
Full analysis set (FAS) was defined according to the intention to treat principle. The FAS consisted of all randomized patients. Following the intention to treat principle patients were analyzed according to the treatment (and stratum) they were assigned to at randomization.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 79 participants 81 participants 160 participants
56.52  (11.978) 58.22  (12.650) 57.38  (12.314)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 79 participants 81 participants 160 participants
Female
40
  50.6%
34
  42.0%
74
  46.3%
Male
39
  49.4%
47
  58.0%
86
  53.8%
1.Primary Outcome
Title Progression-free Survival (PFS) Per Local Radiological Review
Hide Description PFS per RECIST 1.0. (Response Evaluation Criteria in Solid Tumors). PFS was defined as the time from the date of randomization to the date of the first radiologically documented disease progression or death due to any cause.
Time Frame Once 80 PFS events had occurred aproximately after 24 months
Hide Outcome Measure Data
Hide Analysis Population Description

The FAS consisted of all randomized patients. Following the intention to treat principle patients were analyzed according to the treatment (and stratum) they were assigned to at randomization.

One patient in the everolimus + pasireotide LAR treatment arm was untreated due to administrative problems.

Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 79 81
Median (95% Confidence Interval)
Unit of Measure: months
16.82
(12.09 to 19.58)
16.59
(11.07 to 19.48)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Paseriotide LAR + Everolimus, Everolimus
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.488
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.991
Confidence Interval (2-Sided) 95%
0.636 to 1.543
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Safety and Tolerability Profile of Everolimus Alone or in Combination With Pasireotide LAR
Hide Description Consisted of monitoring and recording the rate, type, severity, and causal relationship of adverse events (AEs) and serious AEs (SAEs) to treatment. The safety analysis was based mainly on the frequency of AEs or SAEs and on the number of laboratory values that fell outside of pre-determined range.
Time Frame Once 80 PFS events had occurred
Hide Outcome Measure Data
Hide Analysis Population Description

Safety analysis population included all patients who received any study medication (i.e. at least 1 dose of the study drug in case of monotherapy or at least 1 dose of any 1 compound of the study treatment in case of a combination therapy) with a post-Baseline safety assessment.

See Adverse Events (AE) section for all AEs collected.

Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 78 81
Measure Type: Number
Unit of Measure: Participants
Deaths 7 10
Serious Adverse Events 41 49
Adverse Events 78 81
3.Secondary Outcome
Title Objective Response Rate (ORR) as Per Radiology Review
Hide Description

Objective response was determined by the local radiologist according to the RECIST Version 1.0. ORR is the percentage of patients with a best overall response of complete response (CR) or partial response (PR). This is also referred to as Overall response rate.

CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline.

Time Frame Once 80 PFS events had occurred
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized patients.1 patient in the everolimus + pasireotide LAR treatment arm was untreated due to administrative problems. The study was terminated because the study did not meet its primary objective so minimal efficacy data was obtained.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 79 81
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
20.3
(12.0 to 30.8)
6.2
(2.0 to 13.8)
4.Secondary Outcome
Title Duration of Response (DoR)
Hide Description 80 PFS are expected after approximately 24 months. Kaplan Meier was initially planned to be used to depict duration of response by treatment group and by stratum. Later based on the mode of action of everolimus and pasireotide and based on study experience, only a low number of objective responses per RECIST were expected. Therefore, protocol was amended to only list duration of response, and confirmed responses were flagged in the listing. Hence, statistical analyses were not planned and such data are not available for the following table.
Time Frame Once 80 PFS events had occurred
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized patients. Only a low number of objective responses per RECIST was expected. Therefore, protocol was amended to only list duration of response, and confirmed responses were flagged in the listing. Hence, statistical analyses were not planned and such data are not available for the following table.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
5.Secondary Outcome
Title Overall Survival (OS) Using Kaplan Meier Method
Hide Description Overall survival was defined as the time from date of randomization/start of treatment to date of death due to any cause. If a patient is not known to have died, survival was to be censored at the date of last contact.
Time Frame Once 80 PFS events had occurred
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized patients.1 patient in the everolimus + pasireotide LAR treatment arm was untreated due to administrative problems. The study was terminated because the study did not meet its primary objective so minimal efficacy data was obtained.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 79 81
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
6 months
93.5
(85.0 to 97.2)
93.7
(85.5 to 97.3)
12 months
85.5
(75.4 to 91.7)
86.1
(76.2 to 92.0)
18 months
81.4
(70.6 to 88.5)
75.5
(64.3 to 83.6)
24 months
77.0
(65.6 to 85.1)
71.0
(59.3 to 79.9)
6.Secondary Outcome
Title PFS and the Predictive Probability of Success in Phase III
Hide Description 105 PFS events expected after approximately 36 months
Time Frame Once 105 PFS events had occurred occurred
Hide Outcome Measure Data
Hide Analysis Population Description
Since the study was terminated because the study did not meet its primary objective which was based on PFS as per local radiology assessment, minimal efficacy data was obtained. Only 80 PFS events occurred before study was terminated so 105 PFS events was not reached to analyze this data.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Disease Control Rate (DCR) as Per Radiology Review
Hide Description Disease control rate is the percentage of patients with a best overall response of CR or PR or stable disease (SD) determined by the local radiologist according to the Response Evaluation Criteria In Solid Tumors Criteria (RECIST) Version 1.0. CR: Disappearance of all nontarget lesions. PR: At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the smallest sum of the longest diameter of all target lesions recorded at or after baseline. SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease (PD). PD: Any progression ≤ 18 weeks after randomization (and not qualifying for CR, PR or stable disease SD.
Time Frame Once 80 PFS events had occurred
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS consisted of all randomized patients.1 patient in the everolimus + pasireotide LAR treatment arm was untreated due to administrative problems. The study was terminated because the study did not meet its primary objective so minimal efficacy data was obtained.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 79 81
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
77.2
(66.4 to 85.9)
82.7
(72.7 to 90.2)
8.Secondary Outcome
Title Summary of Pharmacokinetics (PK) for Everolimus for AUClast
Hide Description [Not Specified]
Time Frame Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set consisted of all patients who had at least 1 pasireotide LAR injection or 1 everolimus administration and 1 evaluable concentration data.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 5 8
Mean (Standard Deviation)
Unit of Measure: ng*hr/mL
511  (91.8) 378  (123)
9.Secondary Outcome
Title Summary of Pharmacokinetics (PK) for Everolimus for CL/F
Hide Description [Not Specified]
Time Frame Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set consisted of all patients who had at least 1 pasireotide LAR injection or 1 everolimus administration and 1 evaluable concentration data.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 5 8
Mean (Standard Deviation)
Unit of Measure: L/hr
20.0  (3.21) 29.0  (9.51)
10.Secondary Outcome
Title Summary of Pharmacokinetics (PK) for Everolimus for Cmax and Cmin
Hide Description [Not Specified]
Time Frame Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set consisted of all patients who had at least 1 pasireotide LAR injection or 1 everolimus administration and 1 evaluable concentration data.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 6 9
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cmax 58.7  (25.9) 60.2  (30.6)
Cmin 14.7  (4.81) 7.67  (4.41)
11.Secondary Outcome
Title Summary of Pharmacokinetics (PK) for Everolimus for Tmax
Hide Description [Not Specified]
Time Frame Cycle 2 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set consisted of all patients who had at least 1 pasireotide LAR injection or 1 everolimus administration and 1 evaluable concentration data.
Arm/Group Title Paseriotide LAR + Everolimus Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
everolimus 10 mg once daily po alone
Overall Number of Participants Analyzed 6 9
Median (Inter-Quartile Range)
Unit of Measure: hr
1.00
(0.333 to 5.00)
0.500
(0.500 to 5.00)
12.Secondary Outcome
Title Summary of Pasireotide Concentrations Following Intramuscular Injection of Pasireotide LAR 60mg
Hide Description [Not Specified]
Time Frame Cycle 1 Day 21, Cycle 2 Day 29
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis set consisted of all patients who had at least 1 pasireotide LAR injection or 1 everolimus administration and 1 evaluable concentration data.
Arm/Group Title Paseriotide LAR + Everolimus
Hide Arm/Group Description:
everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im
Overall Number of Participants Analyzed 69
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1 Day 21 (n:69) 21.6  (13.1)
Cycle 2 Day 29 (n: 64) 19.9  (12.1)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Everolimus LAR + Pasireotide Everolimus
Hide Arm/Group Description everolimus 10 mg once daily po in combination with pasireotide LAR 60 mg every 28 days (q28d) im everolimus 10 mg once daily po alone
All-Cause Mortality
Everolimus LAR + Pasireotide Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Everolimus LAR + Pasireotide Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   41/78 (52.56%)   49/81 (60.49%) 
Blood and lymphatic system disorders     
Anaemia  1  0/78 (0.00%)  5/81 (6.17%) 
Leukopenia  1  0/78 (0.00%)  1/81 (1.23%) 
Neutropenia  1  0/78 (0.00%)  1/81 (1.23%) 
Cardiac disorders     
Atrial fibrillation  1  0/78 (0.00%)  1/81 (1.23%) 
Left ventricular dysfunction  1  1/78 (1.28%)  1/81 (1.23%) 
Palpitations  1  1/78 (1.28%)  0/81 (0.00%) 
Tachycardia  1  1/78 (1.28%)  0/81 (0.00%) 
Ventricular fibrillation  1  0/78 (0.00%)  1/81 (1.23%) 
Endocrine disorders     
Hyperparathyroidism  1  0/78 (0.00%)  1/81 (1.23%) 
Eye disorders     
Ocular icterus  1  0/78 (0.00%)  1/81 (1.23%) 
Retinal detachment  1  1/78 (1.28%)  0/81 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  1/78 (1.28%)  5/81 (6.17%) 
Abdominal pain upper  1  1/78 (1.28%)  1/81 (1.23%) 
Anal fistula  1  1/78 (1.28%)  0/81 (0.00%) 
Diarrhoea  1  0/78 (0.00%)  2/81 (2.47%) 
Duodenal stenosis  1  0/78 (0.00%)  1/81 (1.23%) 
Duodenal ulcer  1  0/78 (0.00%)  1/81 (1.23%) 
Gastritis  1  0/78 (0.00%)  1/81 (1.23%) 
Gastrointestinal haemorrhage  1  0/78 (0.00%)  1/81 (1.23%) 
Gastrointestinal oedema  1  0/78 (0.00%)  1/81 (1.23%) 
Haemorrhoids thrombosed  1  1/78 (1.28%)  0/81 (0.00%) 
Hernial eventration  1  1/78 (1.28%)  0/81 (0.00%) 
Ileus  1  1/78 (1.28%)  0/81 (0.00%) 
Intestinal obstruction  1  1/78 (1.28%)  0/81 (0.00%) 
Melaena  1  0/78 (0.00%)  2/81 (2.47%) 
Nausea  1  1/78 (1.28%)  3/81 (3.70%) 
Obstruction gastric  1  1/78 (1.28%)  0/81 (0.00%) 
Oesophagitis  1  0/78 (0.00%)  1/81 (1.23%) 
Pancreatitis acute  1  1/78 (1.28%)  0/81 (0.00%) 
Small intestinal obstruction  1  0/78 (0.00%)  1/81 (1.23%) 
Stomatitis  1  1/78 (1.28%)  0/81 (0.00%) 
Subileus  1  1/78 (1.28%)  0/81 (0.00%) 
Vomiting  1  2/78 (2.56%)  3/81 (3.70%) 
General disorders     
Asthenia  1  0/78 (0.00%)  2/81 (2.47%) 
Device occlusion  1  0/78 (0.00%)  1/81 (1.23%) 
Face oedema  1  0/78 (0.00%)  1/81 (1.23%) 
Fatigue  1  2/78 (2.56%)  1/81 (1.23%) 
General physical health deterioration  1  1/78 (1.28%)  1/81 (1.23%) 
Localised oedema  1  0/78 (0.00%)  1/81 (1.23%) 
Oedema peripheral  1  0/78 (0.00%)  1/81 (1.23%) 
Performance status decreased  1  0/78 (0.00%)  2/81 (2.47%) 
Pyrexia  1  5/78 (6.41%)  6/81 (7.41%) 
Hepatobiliary disorders     
Cholangitis  1  2/78 (2.56%)  3/81 (3.70%) 
Cholangitis acute  1  1/78 (1.28%)  0/81 (0.00%) 
Cholestasis  1  0/78 (0.00%)  2/81 (2.47%) 
Hepatic failure  1  1/78 (1.28%)  0/81 (0.00%) 
Hepatocellular injury  1  1/78 (1.28%)  0/81 (0.00%) 
Hyperbilirubinaemia  1  0/78 (0.00%)  1/81 (1.23%) 
Jaundice  1  1/78 (1.28%)  1/81 (1.23%) 
Jaundice cholestatic  1  1/78 (1.28%)  0/81 (0.00%) 
Infections and infestations     
Appendicitis  1  0/78 (0.00%)  1/81 (1.23%) 
Bacteraemia  1  1/78 (1.28%)  0/81 (0.00%) 
Biliary sepsis  1  0/78 (0.00%)  1/81 (1.23%) 
Biliary tract infection  1  0/78 (0.00%)  1/81 (1.23%) 
Bronchitis  1  0/78 (0.00%)  1/81 (1.23%) 
Device related infection  1  1/78 (1.28%)  0/81 (0.00%) 
Escherichia infection  1  0/78 (0.00%)  1/81 (1.23%) 
Gastroenteritis  1  1/78 (1.28%)  0/81 (0.00%) 
Gastroenteritis aeromonas  1  0/78 (0.00%)  1/81 (1.23%) 
Gastroenteritis norovirus  1  0/78 (0.00%)  1/81 (1.23%) 
Gastroenteritis viral  1  0/78 (0.00%)  1/81 (1.23%) 
Herpes simplex meningoencephalitis  1  0/78 (0.00%)  1/81 (1.23%) 
Infection  1  0/78 (0.00%)  1/81 (1.23%) 
Klebsiella sepsis  1  0/78 (0.00%)  1/81 (1.23%) 
Liver abscess  1  1/78 (1.28%)  0/81 (0.00%) 
Lower respiratory tract infection  1  1/78 (1.28%)  0/81 (0.00%) 
Lower respiratory tract infection bacterial  1  0/78 (0.00%)  1/81 (1.23%) 
Lung infection  1  1/78 (1.28%)  0/81 (0.00%) 
Pneumonia  1  2/78 (2.56%)  2/81 (2.47%) 
Respiratory tract infection  1  0/78 (0.00%)  1/81 (1.23%) 
Sepsis  1  2/78 (2.56%)  4/81 (4.94%) 
Sinusitis  1  0/78 (0.00%)  1/81 (1.23%) 
Tooth abscess  1  1/78 (1.28%)  0/81 (0.00%) 
Urinary tract infection  1  1/78 (1.28%)  1/81 (1.23%) 
Injury, poisoning and procedural complications     
Foreign body aspiration  1  1/78 (1.28%)  0/81 (0.00%) 
Skeletal injury  1  1/78 (1.28%)  0/81 (0.00%) 
Upper limb fracture  1  0/78 (0.00%)  1/81 (1.23%) 
Investigations     
Blood albumin decreased  1  0/78 (0.00%)  1/81 (1.23%) 
Blood bilirubin increased  1  1/78 (1.28%)  0/81 (0.00%) 
Blood creatinine increased  1  2/78 (2.56%)  2/81 (2.47%) 
Blood glucose decreased  1  1/78 (1.28%)  0/81 (0.00%) 
Blood glucose fluctuation  1  1/78 (1.28%)  0/81 (0.00%) 
Blood glucose increased  1  1/78 (1.28%)  0/81 (0.00%) 
Blood lactate dehydrogenase increased  1  0/78 (0.00%)  1/81 (1.23%) 
Blood urea increased  1  1/78 (1.28%)  1/81 (1.23%) 
C-reactive protein increased  1  0/78 (0.00%)  1/81 (1.23%) 
Gamma-glutamyltransferase increased  1  0/78 (0.00%)  1/81 (1.23%) 
Haemoglobin decreased  1  0/78 (0.00%)  1/81 (1.23%) 
Platelet count decreased  1  1/78 (1.28%)  0/81 (0.00%) 
Weight decreased  1  0/78 (0.00%)  2/81 (2.47%) 
Metabolism and nutrition disorders     
Decreased appetite  1  0/78 (0.00%)  1/81 (1.23%) 
Dehydration  1  1/78 (1.28%)  2/81 (2.47%) 
Diabetes mellitus  1  1/78 (1.28%)  1/81 (1.23%) 
Diabetes mellitus inadequate control  1  0/78 (0.00%)  2/81 (2.47%) 
Diabetic ketoacidosis  1  1/78 (1.28%)  0/81 (0.00%) 
Hypercalcaemia  1  0/78 (0.00%)  1/81 (1.23%) 
Hyperglycaemia  1  5/78 (6.41%)  1/81 (1.23%) 
Hypoglycaemia  1  2/78 (2.56%)  1/81 (1.23%) 
Hypokalaemia  1  2/78 (2.56%)  1/81 (1.23%) 
Hypophosphataemia  1  1/78 (1.28%)  0/81 (0.00%) 
Ketoacidosis  1  1/78 (1.28%)  0/81 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/78 (0.00%)  1/81 (1.23%) 
Flank pain  1  1/78 (1.28%)  0/81 (0.00%) 
Musculoskeletal pain  1  1/78 (1.28%)  0/81 (0.00%) 
Osteoarthritis  1  1/78 (1.28%)  0/81 (0.00%) 
Spinal pain  1  1/78 (1.28%)  0/81 (0.00%) 
Synovial cyst  1  0/78 (0.00%)  1/81 (1.23%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cervix carcinoma  1  0/78 (0.00%)  1/81 (1.23%) 
Gastrinoma  1  0/78 (0.00%)  1/81 (1.23%) 
Lipoma  1  0/78 (0.00%)  1/81 (1.23%) 
Tumour pain  1  0/78 (0.00%)  1/81 (1.23%) 
Nervous system disorders     
Cerebral haemorrhage  1  0/78 (0.00%)  1/81 (1.23%) 
Epilepsy  1  1/78 (1.28%)  1/81 (1.23%) 
Headache  1  1/78 (1.28%)  1/81 (1.23%) 
Loss of consciousness  1  1/78 (1.28%)  0/81 (0.00%) 
Nerve compression  1  0/78 (0.00%)  1/81 (1.23%) 
Parkinson's disease  1  1/78 (1.28%)  0/81 (0.00%) 
Sciatica  1  0/78 (0.00%)  1/81 (1.23%) 
Somnolence  1  1/78 (1.28%)  0/81 (0.00%) 
Psychiatric disorders     
Confusional state  1  1/78 (1.28%)  1/81 (1.23%) 
Delirium  1  0/78 (0.00%)  1/81 (1.23%) 
Hallucination  1  1/78 (1.28%)  0/81 (0.00%) 
Psychotic disorder  1  0/78 (0.00%)  1/81 (1.23%) 
Renal and urinary disorders     
Renal failure  1  1/78 (1.28%)  3/81 (3.70%) 
Renal failure acute  1  1/78 (1.28%)  0/81 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea  1  0/78 (0.00%)  3/81 (3.70%) 
Epistaxis  1  0/78 (0.00%)  1/81 (1.23%) 
Lung disorder  1  1/78 (1.28%)  1/81 (1.23%) 
Pharyngeal oedema  1  1/78 (1.28%)  0/81 (0.00%) 
Pleurisy  1  1/78 (1.28%)  0/81 (0.00%) 
Pneumonitis  1  1/78 (1.28%)  1/81 (1.23%) 
Pulmonary embolism  1  1/78 (1.28%)  1/81 (1.23%) 
Skin and subcutaneous tissue disorders     
Dermatitis acneiform  1  1/78 (1.28%)  0/81 (0.00%) 
Vascular disorders     
Hyperaemia  1  0/78 (0.00%)  1/81 (1.23%) 
Hypertension  1  0/78 (0.00%)  1/81 (1.23%) 
Hypotension  1  0/78 (0.00%)  1/81 (1.23%) 
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%
Everolimus LAR + Pasireotide Everolimus
Affected / at Risk (%) Affected / at Risk (%)
Total   77/78 (98.72%)   80/81 (98.77%) 
Blood and lymphatic system disorders     
Anaemia  1  21/78 (26.92%)  20/81 (24.69%) 
Leukopenia  1  3/78 (3.85%)  7/81 (8.64%) 
Lymphopenia  1  4/78 (5.13%)  4/81 (4.94%) 
Thrombocytopenia  1  8/78 (10.26%)  9/81 (11.11%) 
Gastrointestinal disorders     
Abdominal distension  1  7/78 (8.97%)  8/81 (9.88%) 
Abdominal pain  1  22/78 (28.21%)  29/81 (35.80%) 
Abdominal pain upper  1  10/78 (12.82%)  15/81 (18.52%) 
Aphthous stomatitis  1  5/78 (6.41%)  9/81 (11.11%) 
Constipation  1  11/78 (14.10%)  18/81 (22.22%) 
Diarrhoea  1  49/78 (62.82%)  43/81 (53.09%) 
Dysphagia  1  0/78 (0.00%)  5/81 (6.17%) 
Flatulence  1  8/78 (10.26%)  0/81 (0.00%) 
Gastrooesophageal reflux disease  1  3/78 (3.85%)  5/81 (6.17%) 
Mouth ulceration  1  4/78 (5.13%)  6/81 (7.41%) 
Nausea  1  27/78 (34.62%)  24/81 (29.63%) 
Steatorrhoea  1  9/78 (11.54%)  2/81 (2.47%) 
Stomatitis  1  46/78 (58.97%)  51/81 (62.96%) 
Toothache  1  3/78 (3.85%)  5/81 (6.17%) 
Vomiting  1  22/78 (28.21%)  15/81 (18.52%) 
General disorders     
Asthenia  1  17/78 (21.79%)  16/81 (19.75%) 
Fatigue  1  21/78 (26.92%)  27/81 (33.33%) 
Influenza like illness  1  1/78 (1.28%)  7/81 (8.64%) 
Non-cardiac chest pain  1  1/78 (1.28%)  6/81 (7.41%) 
Oedema peripheral  1  26/78 (33.33%)  31/81 (38.27%) 
Peripheral swelling  1  4/78 (5.13%)  4/81 (4.94%) 
Pyrexia  1  15/78 (19.23%)  21/81 (25.93%) 
Infections and infestations     
Cystitis  1  7/78 (8.97%)  3/81 (3.70%) 
Gastroenteritis  1  4/78 (5.13%)  3/81 (3.70%) 
Influenza  1  5/78 (6.41%)  6/81 (7.41%) 
Nasopharyngitis  1  12/78 (15.38%)  10/81 (12.35%) 
Oral herpes  1  3/78 (3.85%)  6/81 (7.41%) 
Pharyngitis  1  5/78 (6.41%)  2/81 (2.47%) 
Pneumonia  1  1/78 (1.28%)  5/81 (6.17%) 
Rhinitis  1  1/78 (1.28%)  5/81 (6.17%) 
Upper respiratory tract infection  1  5/78 (6.41%)  6/81 (7.41%) 
Urinary tract infection  1  4/78 (5.13%)  5/81 (6.17%) 
Investigations     
Alanine aminotransferase increased  1  5/78 (6.41%)  4/81 (4.94%) 
Aspartate aminotransferase increased  1  6/78 (7.69%)  2/81 (2.47%) 
Blood alkaline phosphatase increased  1  5/78 (6.41%)  4/81 (4.94%) 
Blood lactate dehydrogenase increased  1  4/78 (5.13%)  1/81 (1.23%) 
Gamma-glutamyltransferase increased  1  9/78 (11.54%)  11/81 (13.58%) 
Glycosylated haemoglobin increased  1  4/78 (5.13%)  1/81 (1.23%) 
Haemoglobin decreased  1  2/78 (2.56%)  7/81 (8.64%) 
Weight decreased  1  24/78 (30.77%)  25/81 (30.86%) 
Metabolism and nutrition disorders     
Decreased appetite  1  14/78 (17.95%)  22/81 (27.16%) 
Diabetes mellitus  1  20/78 (25.64%)  6/81 (7.41%) 
Hypercholesterolaemia  1  16/78 (20.51%)  15/81 (18.52%) 
Hyperglycaemia  1  56/78 (71.79%)  23/81 (28.40%) 
Hypertriglyceridaemia  1  10/78 (12.82%)  7/81 (8.64%) 
Hypoglycaemia  1  16/78 (20.51%)  3/81 (3.70%) 
Hypokalaemia  1  5/78 (6.41%)  11/81 (13.58%) 
Hyponatraemia  1  4/78 (5.13%)  2/81 (2.47%) 
Hypophosphataemia  1  9/78 (11.54%)  3/81 (3.70%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  11/78 (14.10%)  13/81 (16.05%) 
Back pain  1  11/78 (14.10%)  14/81 (17.28%) 
Muscle spasms  1  6/78 (7.69%)  4/81 (4.94%) 
Musculoskeletal pain  1  4/78 (5.13%)  5/81 (6.17%) 
Myalgia  1  6/78 (7.69%)  7/81 (8.64%) 
Neck pain  1  2/78 (2.56%)  5/81 (6.17%) 
Pain in extremity  1  11/78 (14.10%)  8/81 (9.88%) 
Nervous system disorders     
Dizziness  1  4/78 (5.13%)  5/81 (6.17%) 
Dysgeusia  1  10/78 (12.82%)  17/81 (20.99%) 
Headache  1  17/78 (21.79%)  26/81 (32.10%) 
Paraesthesia  1  3/78 (3.85%)  5/81 (6.17%) 
Psychiatric disorders     
Anxiety  1  4/78 (5.13%)  4/81 (4.94%) 
Insomnia  1  7/78 (8.97%)  8/81 (9.88%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  21/78 (26.92%)  28/81 (34.57%) 
Dyspnoea  1  5/78 (6.41%)  12/81 (14.81%) 
Epistaxis  1  5/78 (6.41%)  20/81 (24.69%) 
Oropharyngeal pain  1  4/78 (5.13%)  6/81 (7.41%) 
Pneumonitis  1  5/78 (6.41%)  11/81 (13.58%) 
Skin and subcutaneous tissue disorders     
Acne  1  1/78 (1.28%)  7/81 (8.64%) 
Dermatitis  1  4/78 (5.13%)  3/81 (3.70%) 
Dermatitis acneiform  1  6/78 (7.69%)  7/81 (8.64%) 
Dry skin  1  12/78 (15.38%)  19/81 (23.46%) 
Nail disorder  1  4/78 (5.13%)  5/81 (6.17%) 
Onychoclasis  1  5/78 (6.41%)  8/81 (9.88%) 
Pruritus  1  12/78 (15.38%)  18/81 (22.22%) 
Rash  1  20/78 (25.64%)  25/81 (30.86%) 
Vascular disorders     
Hypertension  1  15/78 (19.23%)  14/81 (17.28%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
A planned primary analysis was completed with data cut of 02-Apr-2014. The study did not meet its primary objective, which was based on progression-free survival as per local radiology assessment and was prematurely terminated.
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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: trialandresults.registries@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01374451     History of Changes
Other Study ID Numbers: CSOM230I2201
2010-023183-40 ( EudraCT Number )
First Submitted: June 14, 2011
First Posted: June 16, 2011
Results First Submitted: February 16, 2016
Results First Posted: December 20, 2016
Last Update Posted: December 20, 2016