Trial Outcomes & Findings for Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy (NCT NCT00363051)

Last Updated: 2013-05-10

Results Overview

Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

160 participants

Primary outcome timeframe

from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months)

Results posted on

2013-05-10

Participant Flow

Participant milestones

Participant milestones
Measure	Stratum 1: Everolimus 10 mg Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Overall Study STARTED	115	45
Overall Study COMPLETED	77	23
Overall Study NOT COMPLETED	38	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Stratum 1: Everolimus 10 mg Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Overall Study Adminstrative problems	1	1
Overall Study Adverse Event	21	12
Overall Study New Cancer Therapy	2	1
Overall Study Withdrawal by Subject	11	3
Overall Study Lost to Follow-up	0	1
Overall Study Protocol Violation	0	2
Overall Study Death	3	2

Baseline Characteristics

Safety/Efficacy of Everolimus in Adults With Advanced Pancreatic Neuroendocrine Cancer Not Responsive to Chemotherapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stratum 1: Everolimus 10 mg n=115 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot n=45 Participants Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot.	Total n=160 Participants Total of all reporting groups
Age Continuous	55.1 years STANDARD_DEVIATION 11.8 • n=5 Participants	53.64 years STANDARD_DEVIATION 12.478 • n=7 Participants	54.33 years STANDARD_DEVIATION 11.98 • n=5 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	21 Participants n=7 Participants	70 Participants n=5 Participants
Sex: Female, Male Male	66 Participants n=5 Participants	24 Participants n=7 Participants	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: from date of randomization/start of treatment until first documented response confirmed 4 weeks later( at least 3 months)

Population: The full analysis set (FAS) consisted of all patients who received at least one dose of everolimus.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=115 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)	9.6 percentage of participants Interval 4.9 to 16.5	—

SECONDARY outcome

Timeframe: from date of first documented confirmed response to time to progression, at least 3 months

Population: Full Analysis Set (FAS) consisted of all patients who received at least one dose of everolimus. Only those patients whose best overall response was complete response (CR) or partial response (PR) were included in this analysis.

Duration of overall response applies only to patients whose best overall response was complete response (CR) or partial response (PR): * Complete Response (CR) = at least two determinations of CR at least 4 weeks apart before progression. * Partial response (PR) = at least two determinations of PR or better at least 4 weeks apart before progression. Progression = 20% increase in the sum of the longest diameter of all target lesions, from the smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=11 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Duration of Overall Response (Stratum 1) Based on Response Evaluation Criteria in Solid Tumors (RECIST)- Central Radiology Review	10.64 Months Interval 9.79 to The upper limit was not estimable in the study as it is longer than duration of study.	—

SECONDARY outcome

Timeframe: from date of first documented confirmed response to time to progression, at least 3 months

Population: Very low number of patients demonstrated a partial response, the median duration of response as per central review has not been calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from date of randomization/start of treatment until first documented response confirmed 4 weeks later (at least 3 months)

Population: Full Analysis Set (FAS) was consisted of all patients who received at least one dose of everolimus.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=45 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Objective Response Rate: Percentage of Participants With Best Over All Response of Complete Response or Partial Response by Central Radiology Review (Stratum 2) Based on Response Evaluation Criteria in Solid Tumors (RECIST)	4.4 percentage of participants Interval 0.5 to 15.1	—

SECONDARY outcome

Timeframe: on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

Population: The safety population consists of all patients who received at least one dose of everolimus and had at least one post-baseline safety assessment.

Adverse events are defined as any unfavorable and unintended diagnosis, symptom, sign (including an abnormal laboratory finding), syndrome or disease which either occurs during study, having been absent at baseline, or, if present at baseline, appears to worsen. Serious adverse events are any untoward medical occurrences that result in death, are life threatening, require (or prolong) hospitalization, cause persistent or significant disability/incapacity, result in congenital anomalies or birth defects, or are other conditions which in judgment of investigators represent significant hazards.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=115 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1] Adverse Events	115 Participants	—
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1] Death	10 Participants	—
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs)[Stratum 1] Serious Adverse Events	63 Participants	—

SECONDARY outcome

Timeframe: on or after the day of the first intake of study treatment to starting no later than 28 days after study treatment discontinuation, at least every month

Population: The safety population consists of all patients who received at least one dose of everolimus and had at least one post-baseline safety assessment.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=45 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2] Adverse Events	45 Participants	—
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2] Death	2 Participants	—
Number of Participants With Adverse Events (AEs), Death, Serious Adverse Events (SAEs) [Stratum 2] Serious Adverse Events	27 Participants	—

SECONDARY outcome

Timeframe: from randomisation to dates of disease progression, death from any cause or last tumor assessment, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 September 2010

Population: The full analysis set (FAS) consisted of all patients who received at least one dose of everolimus.

Progression free survival (PFS) is defined as the time from randomization to the date of first documented disease progression or death from any cause. The Kaplan-Meier estimate of the PFS survival function was constructed. Median PFS was obtained and displayed along with 95% confidence intervals.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=115 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 1)	9.69 Months Interval 8.25 to 13.31	—

SECONDARY outcome

Population: The full analysis set (FAS) consisted of all patients who received at least one dose of everolimus.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=45 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Time to Progression Free Survival (PFS) Per Central Radiology Review (Stratum 2)	16.69 Months Interval 11.07 to The upper limit was not estimable in the study as it is longer than duration of study.	—

SECONDARY outcome

Timeframe: from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012

Population: The full analysis set consisted of all patients who received at least one dose of everolimus.

Overall survival measures the time of survival , with any response or disease progression, until death. The OS is defined as the time from date of start of treatment to date of death due to any cause. If a patient is not known to have died, survival was censored at the date of last contact. In each treatment stratum, the Kaplan-Meier estimate of the overall survival function was constructed.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=115 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Time to Overall Survival (OS)(Stratum 1)	28.78 months Interval 20.24 to 36.37	—

SECONDARY outcome

Timeframe: from randomisation to dates of disease progression, death from any cause, reported between day of first patient randomised, 26 June 2006, until cut-off date 13 April 2012

Population: The full analysis set consisted of all patients who received at least one dose of everolimus.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=45 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Time to Overall Survival (OS) (Stratum 2)	38.77 months Interval 29.08 to The upper limit was not estimable in the study as it is longer than duration of study.	—

SECONDARY outcome

Timeframe: Cycle 1 Day 15

Population: Full Analysis Set (FAS) is consisted of all patients who received at least one dose of everolimus. Patients with everolimus pharmacokinteic samples, with nonzero concentration, at Cycle 1 Day 15 were included

For all patients in both strata, a blood sample for everolimus trough level determination will be collected immediately prior to the everolimus administration on Cycle 1 Day 15, Cycle 2 Day 1, and every month thereafter. A treatment cycle was defined as 28 days of consecutive daily treatment with everolimus and treatment continued until tumor progression. It is critical that patients not take their daily everolimus dose before the sample is drawn.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=92 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot n=30 Participants Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Everolimus Trough Level Determination by Pharmacokinetics Parameter in Both Strata (Stratum 1 and 2)	15.7 ng/ml Standard Deviation 15.82	17.3 ng/ml Standard Deviation 18.08

SECONDARY outcome

Timeframe: Cycle 1 Day 1, Cycle 2 Day 1

Population: Full Analysis Set (FAS) is consisted of all patients who received at least one dose of everolimus. Patients with Octreotide Depot pharmacokinetic samples, with nonzero concentration, at Cycle 1 Day 1 or Cycle 2 Day 1 were included.

The effect of Octreotide Depot on the trough concentrations of everolimus was assessed at Cycle 1 Day 15.

Outcome measures

Outcome measures
Measure	Stratum 1: Everolimus 10 mg n=38 Participants Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.
Effect of Octreotide Depot on the Trough Concentrations of Everolimus Cycle 1 Day 1 (pre-treatment baseline) (n=37)	3.2 ng/ml Standard Deviation 2.81	—
Effect of Octreotide Depot on the Trough Concentrations of Everolimus Cycle 2 Day 1 (n= 38)	3.7 ng/ml Standard Deviation 3.47	—

Adverse Events

Stratum 1: Everolimus 10 mg

Serious events: 63 serious events

Other events: 115 other events

Deaths: 0 deaths

Stratum 2: Everolimus 10 mg + Octreotide Depot

Serious events: 27 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Stratum 1: Everolimus 10 mg n=115 participants at risk Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot n=45 participants at risk Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot.
Blood and lymphatic system disorders Anaemia	2.6% 3/115	0.00% 0/45
Blood and lymphatic system disorders Lymphopenia	0.87% 1/115	0.00% 0/45
Blood and lymphatic system disorders Neutropenia	0.00% 0/115	2.2% 1/45
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/115	6.7% 3/45
Cardiac disorders Acute myocardial infarction	0.00% 0/115	2.2% 1/45
Cardiac disorders Cardiac failure	0.87% 1/115	6.7% 3/45
Cardiac disorders Cardiac failure congestive	0.00% 0/115	4.4% 2/45
Cardiac disorders Cardio-respiratory arrest	0.87% 1/115	0.00% 0/45
Cardiac disorders Myocardial infarction	0.00% 0/115	2.2% 1/45
Cardiac disorders Tachycardia	0.00% 0/115	2.2% 1/45
Congenital, familial and genetic disorders Gastrointestinal angiodysplasia	0.87% 1/115	0.00% 0/45
Eye disorders Optic ischaemic neuropathy	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Abdominal distension	0.00% 0/115	2.2% 1/45
Gastrointestinal disorders Abdominal pain	8.7% 10/115	8.9% 4/45
Gastrointestinal disorders Abdominal pain upper	1.7% 2/115	0.00% 0/45
Gastrointestinal disorders Ascites	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Colitis	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Diarrhoea	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Gastritis	0.87% 1/115	2.2% 1/45
Gastrointestinal disorders Gastrointestinal haemorrhage	1.7% 2/115	0.00% 0/45
Gastrointestinal disorders Inguinal hernia	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Intestinal ischaemia	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Intestinal obstruction	0.00% 0/115	2.2% 1/45
Gastrointestinal disorders Nausea	2.6% 3/115	4.4% 2/45
Gastrointestinal disorders Small intestinal obstruction	1.7% 2/115	0.00% 0/45
Gastrointestinal disorders Subileus	1.7% 2/115	0.00% 0/45
Gastrointestinal disorders Swollen tongue	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.87% 1/115	0.00% 0/45
Gastrointestinal disorders Vomiting	3.5% 4/115	6.7% 3/45
General disorders Asthenia	5.2% 6/115	0.00% 0/45
General disorders Device dislocation	0.87% 1/115	0.00% 0/45
General disorders Device occlusion	0.87% 1/115	0.00% 0/45
General disorders Fatigue	3.5% 4/115	0.00% 0/45
General disorders General physical health deterioration	1.7% 2/115	0.00% 0/45
General disorders Hyperthermia	0.87% 1/115	2.2% 1/45
General disorders Hypothermia	0.87% 1/115	0.00% 0/45
General disorders Local swelling	0.87% 1/115	0.00% 0/45
General disorders Multi-organ failure	0.87% 1/115	2.2% 1/45
General disorders Non-cardiac chest pain	0.87% 1/115	2.2% 1/45
General disorders Oedema peripheral	0.00% 0/115	4.4% 2/45
General disorders Performance status decreased	1.7% 2/115	0.00% 0/45
General disorders Pyrexia	5.2% 6/115	4.4% 2/45
General disorders Systemic inflammatory response syndrome	0.87% 1/115	0.00% 0/45
Hepatobiliary disorders Bile duct obstruction	0.87% 1/115	2.2% 1/45
Hepatobiliary disorders Cholangitis	3.5% 4/115	0.00% 0/45
Hepatobiliary disorders Cholelithiasis	0.87% 1/115	0.00% 0/45
Hepatobiliary disorders Hepatic failure	0.87% 1/115	0.00% 0/45
Hepatobiliary disorders Jaundice	0.87% 1/115	0.00% 0/45
Hepatobiliary disorders Jaundice cholestatic	0.87% 1/115	0.00% 0/45
Hepatobiliary disorders Portal vein thrombosis	1.7% 2/115	0.00% 0/45
Immune system disorders Anaphylactic reaction	0.00% 0/115	2.2% 1/45
Infections and infestations Abscess soft tissue	0.87% 1/115	0.00% 0/45
Infections and infestations Bacteraemia	0.87% 1/115	0.00% 0/45
Infections and infestations Bacterial infection	0.87% 1/115	0.00% 0/45
Infections and infestations Biliary tract infection	0.00% 0/115	2.2% 1/45
Infections and infestations Bronchitis	0.87% 1/115	2.2% 1/45
Infections and infestations Cellulitis	0.00% 0/115	2.2% 1/45
Infections and infestations Device related infection	0.87% 1/115	2.2% 1/45
Infections and infestations Diverticulitis	0.87% 1/115	0.00% 0/45
Infections and infestations Escherichia infection	0.00% 0/115	2.2% 1/45
Infections and infestations Folliculitis	0.87% 1/115	0.00% 0/45
Infections and infestations Gastroenteritis	0.87% 1/115	0.00% 0/45
Infections and infestations Gastroenteritis viral	0.87% 1/115	0.00% 0/45
Infections and infestations Infection	0.87% 1/115	0.00% 0/45
Infections and infestations Influenza	0.87% 1/115	0.00% 0/45
Infections and infestations Liver abscess	0.87% 1/115	0.00% 0/45
Infections and infestations Lobar pneumonia	1.7% 2/115	0.00% 0/45
Infections and infestations Lung infection	0.87% 1/115	0.00% 0/45
Infections and infestations Peritonitis bacterial	0.87% 1/115	0.00% 0/45
Infections and infestations Pharyngitis streptococcal	0.87% 1/115	0.00% 0/45
Infections and infestations Pneumocystis jiroveci pneumonia	0.87% 1/115	0.00% 0/45
Infections and infestations Pneumonia	4.3% 5/115	2.2% 1/45
Infections and infestations Post procedural infection	0.00% 0/115	2.2% 1/45
Infections and infestations Pyelonephritis	0.87% 1/115	0.00% 0/45
Infections and infestations Sepsis	2.6% 3/115	2.2% 1/45
Infections and infestations Sepsis syndrome	0.87% 1/115	0.00% 0/45
Infections and infestations Serratia infection	0.00% 0/115	2.2% 1/45
Infections and infestations Sinusitis	0.87% 1/115	0.00% 0/45
Infections and infestations Soft tissue infection	0.87% 1/115	0.00% 0/45
Infections and infestations Staphylococcal infection	0.87% 1/115	0.00% 0/45
Infections and infestations Subcutaneous abscess	0.00% 0/115	2.2% 1/45
Injury, poisoning and procedural complications Accidental overdose	0.87% 1/115	0.00% 0/45
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.87% 1/115	0.00% 0/45
Injury, poisoning and procedural complications Radiation oesophagitis	0.00% 0/115	2.2% 1/45
Investigations Ammonia increased	0.87% 1/115	0.00% 0/45
Investigations Blood creatinine increased	0.00% 0/115	2.2% 1/45
Investigations Haematocrit decreased	0.00% 0/115	2.2% 1/45
Metabolism and nutrition disorders Cachexia	0.87% 1/115	0.00% 0/45
Metabolism and nutrition disorders Decreased appetite	3.5% 4/115	0.00% 0/45
Metabolism and nutrition disorders Dehydration	2.6% 3/115	4.4% 2/45
Metabolism and nutrition disorders Diabetes mellitus	0.87% 1/115	0.00% 0/45
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/115	2.2% 1/45
Metabolism and nutrition disorders Hypoglycaemia	0.87% 1/115	2.2% 1/45
Metabolism and nutrition disorders Hyponatraemia	0.87% 1/115	2.2% 1/45
Metabolism and nutrition disorders Malnutrition	2.6% 3/115	0.00% 0/45
Musculoskeletal and connective tissue disorders Arthralgia	0.87% 1/115	0.00% 0/45
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/115	2.2% 1/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder transitional cell carcinoma	0.00% 0/115	2.2% 1/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/115	2.2% 1/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.87% 1/115	0.00% 0/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon cancer	0.87% 1/115	0.00% 0/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.87% 1/115	0.00% 0/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to small intestine	0.87% 1/115	0.00% 0/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to spine	0.87% 1/115	0.00% 0/45
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour necrosis	0.87% 1/115	0.00% 0/45
Nervous system disorders Altered state of consciousness	0.87% 1/115	0.00% 0/45
Nervous system disorders Cerebral haemorrhage	0.87% 1/115	0.00% 0/45
Nervous system disorders Cerebrovascular accident	1.7% 2/115	0.00% 0/45
Nervous system disorders Coma hepatic	0.87% 1/115	0.00% 0/45
Nervous system disorders Hepatic encephalopathy	0.00% 0/115	2.2% 1/45
Nervous system disorders Hyperaesthesia	0.87% 1/115	0.00% 0/45
Nervous system disorders Loss of consciousness	0.00% 0/115	2.2% 1/45
Nervous system disorders Metabolic encephalopathy	0.87% 1/115	0.00% 0/45
Nervous system disorders Unresponsive to stimuli	0.00% 0/115	2.2% 1/45
Nervous system disorders Visual field defect	0.87% 1/115	0.00% 0/45
Psychiatric disorders Confusional state	1.7% 2/115	2.2% 1/45
Psychiatric disorders Depression	0.87% 1/115	0.00% 0/45
Psychiatric disorders Insomnia	0.87% 1/115	0.00% 0/45
Psychiatric disorders Mental status changes	0.87% 1/115	0.00% 0/45
Renal and urinary disorders Dysuria	0.00% 0/115	2.2% 1/45
Renal and urinary disorders Pollakiuria	0.00% 0/115	2.2% 1/45
Renal and urinary disorders Renal failure	1.7% 2/115	6.7% 3/45
Renal and urinary disorders Renal failure acute	0.00% 0/115	2.2% 1/45
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.87% 1/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Aspiration	0.87% 1/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Cough	0.87% 1/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.5% 4/115	6.7% 3/45
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.87% 1/115	2.2% 1/45
Respiratory, thoracic and mediastinal disorders Hydropneumothorax	0.87% 1/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.87% 1/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Lung consolidation	0.00% 0/115	2.2% 1/45
Respiratory, thoracic and mediastinal disorders Lung disorder	0.87% 1/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/115	4.4% 2/45
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.87% 1/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Pneumonitis	1.7% 2/115	0.00% 0/45
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.87% 1/115	4.4% 2/45
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/115	2.2% 1/45
Respiratory, thoracic and mediastinal disorders Pulmonary infarction	0.00% 0/115	2.2% 1/45
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.87% 1/115	2.2% 1/45
Skin and subcutaneous tissue disorders Rash	0.87% 1/115	0.00% 0/45
Skin and subcutaneous tissue disorders Swelling face	0.00% 0/115	2.2% 1/45
Vascular disorders Deep vein thrombosis	0.00% 0/115	2.2% 1/45
Vascular disorders Hypotension	0.87% 1/115	0.00% 0/45

Other adverse events

Other adverse events
Measure	Stratum 1: Everolimus 10 mg n=115 participants at risk Stratum 1 patients who were not receiving regular Octreotide Depot therapy. These patients were to receive everolimus monotherapy at 10 mg/day. Patients were instructed to take two 5 mg tablets of everolimus orally with a glass of water, once daily (preferably in the morning). Dosing was strongly recommended to occur at the same time every day.	Stratum 2: Everolimus 10 mg + Octreotide Depot n=45 participants at risk Stratum 2 participants who had received at least three consecutive months of Octreotide Long Acting Depot therapy prior to enrollment. These patients also received Everolimus 10 mg/day in addition to continuing their entry dose of Octreotide Depot.
Blood and lymphatic system disorders Anaemia	19.1% 22/115	24.4% 11/45
Blood and lymphatic system disorders Leukopenia	8.7% 10/115	4.4% 2/45
Blood and lymphatic system disorders Lymphopenia	8.7% 10/115	0.00% 0/45
Blood and lymphatic system disorders Neutropenia	8.7% 10/115	11.1% 5/45
Blood and lymphatic system disorders Thrombocytopenia	9.6% 11/115	13.3% 6/45
Eye disorders Conjunctivitis	3.5% 4/115	8.9% 4/45
Eye disorders Vision blurred	0.00% 0/115	8.9% 4/45
Gastrointestinal disorders Abdominal distension	7.8% 9/115	11.1% 5/45
Gastrointestinal disorders Abdominal pain	33.0% 38/115	20.0% 9/45
Gastrointestinal disorders Abdominal pain upper	21.7% 25/115	15.6% 7/45
Gastrointestinal disorders Aphthous stomatitis	20.9% 24/115	13.3% 6/45
Gastrointestinal disorders Ascites	7.8% 9/115	0.00% 0/45
Gastrointestinal disorders Constipation	26.1% 30/115	17.8% 8/45
Gastrointestinal disorders Diarrhoea	54.8% 63/115	55.6% 25/45
Gastrointestinal disorders Dry mouth	6.1% 7/115	4.4% 2/45
Gastrointestinal disorders Dyspepsia	5.2% 6/115	2.2% 1/45
Gastrointestinal disorders Flatulence	5.2% 6/115	8.9% 4/45
Gastrointestinal disorders Haemorrhoids	1.7% 2/115	6.7% 3/45
Gastrointestinal disorders Mouth ulceration	6.1% 7/115	4.4% 2/45
Gastrointestinal disorders Nausea	47.0% 54/115	48.9% 22/45
Gastrointestinal disorders Steatorrhoea	0.87% 1/115	6.7% 3/45
Gastrointestinal disorders Stomatitis	49.6% 57/115	53.3% 24/45
Gastrointestinal disorders Toothache	6.1% 7/115	4.4% 2/45
Gastrointestinal disorders Vomiting	34.8% 40/115	26.7% 12/45
General disorders Asthenia	33.0% 38/115	20.0% 9/45
General disorders Chills	8.7% 10/115	8.9% 4/45
General disorders Fatigue	46.1% 53/115	44.4% 20/45
General disorders Non-cardiac chest pain	5.2% 6/115	2.2% 1/45
General disorders Oedema peripheral	29.6% 34/115	31.1% 14/45
General disorders Pain	6.1% 7/115	6.7% 3/45
General disorders Pyrexia	35.7% 41/115	31.1% 14/45
Infections and infestations Bronchitis	3.5% 4/115	8.9% 4/45
Infections and infestations Influenza	6.1% 7/115	8.9% 4/45
Infections and infestations Nasopharyngitis	15.7% 18/115	11.1% 5/45
Infections and infestations Pneumonia	3.5% 4/115	6.7% 3/45
Infections and infestations Rhinitis	6.1% 7/115	4.4% 2/45
Infections and infestations Sinusitis	10.4% 12/115	8.9% 4/45
Infections and infestations Upper respiratory tract infection	9.6% 11/115	8.9% 4/45
Infections and infestations Urinary tract infection	9.6% 11/115	11.1% 5/45
Injury, poisoning and procedural complications Fall	0.00% 0/115	8.9% 4/45
Investigations Alanine aminotransferase increased	6.1% 7/115	2.2% 1/45
Investigations Aspartate aminotransferase increased	6.1% 7/115	0.00% 0/45
Investigations Blood alkaline phosphatase increased	7.8% 9/115	2.2% 1/45
Investigations Blood creatinine increased	0.87% 1/115	13.3% 6/45
Investigations Haemoglobin decreased	3.5% 4/115	6.7% 3/45
Investigations International normalised ratio increased	0.87% 1/115	6.7% 3/45
Investigations Weight decreased	27.8% 32/115	26.7% 12/45
Metabolism and nutrition disorders Decreased appetite	23.5% 27/115	22.2% 10/45
Metabolism and nutrition disorders Dehydration	4.3% 5/115	13.3% 6/45
Metabolism and nutrition disorders Diabetes mellitus	9.6% 11/115	2.2% 1/45
Metabolism and nutrition disorders Hypercholesterolaemia	12.2% 14/115	4.4% 2/45
Metabolism and nutrition disorders Hyperglycaemia	18.3% 21/115	20.0% 9/45
Metabolism and nutrition disorders Hypoglycaemia	7.8% 9/115	6.7% 3/45
Metabolism and nutrition disorders Hypokalaemia	13.0% 15/115	11.1% 5/45
Metabolism and nutrition disorders Hyponatraemia	6.1% 7/115	2.2% 1/45
Metabolism and nutrition disorders Hypophosphataemia	9.6% 11/115	8.9% 4/45
Musculoskeletal and connective tissue disorders Arthralgia	13.0% 15/115	26.7% 12/45
Musculoskeletal and connective tissue disorders Back pain	24.3% 28/115	20.0% 9/45
Musculoskeletal and connective tissue disorders Muscle spasms	5.2% 6/115	4.4% 2/45
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.0% 8/115	4.4% 2/45
Musculoskeletal and connective tissue disorders Myalgia	10.4% 12/115	8.9% 4/45
Musculoskeletal and connective tissue disorders Neck pain	7.0% 8/115	6.7% 3/45
Musculoskeletal and connective tissue disorders Pain in extremity	4.3% 5/115	13.3% 6/45
Nervous system disorders Dizziness	4.3% 5/115	15.6% 7/45
Nervous system disorders Dysgeusia	12.2% 14/115	15.6% 7/45
Nervous system disorders Headache	34.8% 40/115	20.0% 9/45
Psychiatric disorders Anxiety	7.0% 8/115	6.7% 3/45
Psychiatric disorders Confusional state	5.2% 6/115	4.4% 2/45
Psychiatric disorders Depression	8.7% 10/115	4.4% 2/45
Psychiatric disorders Insomnia	13.0% 15/115	11.1% 5/45
Renal and urinary disorders Nocturia	1.7% 2/115	8.9% 4/45
Respiratory, thoracic and mediastinal disorders Cough	27.0% 31/115	17.8% 8/45
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.7% 18/115	24.4% 11/45
Respiratory, thoracic and mediastinal disorders Epistaxis	14.8% 17/115	11.1% 5/45
Respiratory, thoracic and mediastinal disorders Lung disorder	3.5% 4/115	6.7% 3/45
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	7.0% 8/115	20.0% 9/45
Respiratory, thoracic and mediastinal disorders Pleural effusion	3.5% 4/115	6.7% 3/45
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.3% 5/115	8.9% 4/45
Skin and subcutaneous tissue disorders Acne	6.1% 7/115	4.4% 2/45
Skin and subcutaneous tissue disorders Dermatitis acneiform	1.7% 2/115	11.1% 5/45
Skin and subcutaneous tissue disorders Dry skin	13.0% 15/115	15.6% 7/45
Skin and subcutaneous tissue disorders Erythema	4.3% 5/115	11.1% 5/45
Skin and subcutaneous tissue disorders Hyperhidrosis	5.2% 6/115	2.2% 1/45
Skin and subcutaneous tissue disorders Nail disorder	7.8% 9/115	4.4% 2/45
Skin and subcutaneous tissue disorders Pruritus	15.7% 18/115	15.6% 7/45
Skin and subcutaneous tissue disorders Rash	47.0% 54/115	46.7% 21/45
Vascular disorders Hypertension	11.3% 13/115	8.9% 4/45

Additional Information

Novartis Study Director

Novartis Pharmaceuticals

Phone: (862 778-8300

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis's agreements with it's investigators vary. However, Novartis does not prohibit any investigator from publishing. Any publication from a single-center site is postponed until the publication of the pooled data ( i.e. data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER