Clinical Trial Results:
Phase II, open, single group, multicentre study to evaluate the efficacy and safety of Lanreotide Autogel® (120 mg) administered every 4 weeks by deep subcutaneous injection in the tumour´s growth stabilization of patients with progressive neuroendocrine tumours who are not eligible to be treated with either surgery or chemotherapy

Summary
EudraCT number
2004-002871-18
Trial protocol
ES  
Global end of trial date
06 Nov 2009

Results information
Results version number
v1(current)
This version publication date
14 May 2016
First version publication date
14 May 2016
Other versions

Trial information

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Trial identification
Sponsor protocol code
A-92-52030-166
Additional study identifiers
ISRCTN number
-
US NCT number
-
WHO universal trial number (UTN)
-
Sponsors
Sponsor organisation name
Ipsen Pharma
Sponsor organisation address
65, Quai Georges Gorse, Boulogne-Billancourt Cedex, France, 92650
Public contact
Medical Director, Neurosurgery., Ipsen Pharma, [email protected]
Scientific contact
Medical Director, Neurosurgery., Ipsen Pharma, [email protected]
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)
No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
No
Results analysis stage
Analysis stage
Final
Date of interim/final analysis
23 Dec 2010
Is this the analysis of the primary completion data?
Yes
Primary completion date
06 Nov 2009
Global end of trial reached?
Yes
Global end of trial date
06 Nov 2009
Was the trial ended prematurely?
No
General information about the trial
Main objective of the trial
To evaluate the efficacy of Somatulina Autogel® in tumour growth stabilisation, in patients with progressive neuroendocrine tumours who are not eligible to be treated with either surgery or chemotherapy at the time of their inclusion in the study.
Protection of trial subjects
This clinical study was designed and implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 21 and with the ethical principles laid down in the Declaration of Helsinki.
Background therapy
-
Evidence for comparator
-
Actual start date of recruitment
05 May 2006
Long term follow-up planned
Yes
Long term follow-up rationale
Safety, Efficacy
Long term follow-up duration
22 Months
Independent data monitoring committee (IDMC) involvement?
No
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled
Spain: 30
Worldwide total number of subjects
30
EEA total number of subjects
30
Number of subjects enrolled per age group
In utero
0
Preterm newborn - gestational age
0
Newborns (0-27 days)
0
Infants and toddlers (28 days-23 months)
0
Children (2-11 years)
0
Adolescents (12-17 years)
0
Adults (18-64 years)
17
From 65 to 84 years
13
85 years and over
0

Subject disposition

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Recruitment
Recruitment details
Thirty patients from 17 Spanish investigational centres were included in this study, with a maximum of four patients recruited by each of three centres.

Pre-assignment
Screening details
Thirty patients were screened and all thirty were included in the study.

Period 1
Period 1 title
Overall Trial (overall period)
Is this the baseline period?
Yes
Allocation method
Non-randomised - controlled
Blinding used
Not blinded

Arms
Arm title
All Subjects
Arm description
Lanreotide Autogel 120mg
Arm type
Experimental

Investigational medicinal product name
Lanreotide Autogel
Investigational medicinal product code
Other name
Pharmaceutical forms
Solution for injection
Routes of administration
Subcutaneous use
Dosage and administration details
Lanreotide Autogel 120 mg single deep subcutaneous (s.c.) injection every 4 week (28±5 days) intervals up to 23 doses

Number of subjects in period 1
All Subjects
Started
30
Completed
3
Not completed
27
     Death
1
     Protocol deviation
1
     Disease progression
21
     Patient decision
1
     Adverse Event
2
     Not Specified
1

Baseline characteristics

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Baseline characteristics reporting groups
Reporting group title
Overall Trial
Reporting group description
Lanreotide Autogel 120 mg single deep subcutaneous (s.c.) injection every 4 week (28±5 days) intervals up to 23 doses

Reporting group values
Overall Trial Total
Number of subjects
30 30
Age categorical
Units: Subjects
Age continuous
Intent-To-Treat (ITT) population are patients who have received at least one dose of lanreotide Autogel®.
Units: years
    arithmetic mean (standard deviation)
62.4 ± 10.3 -
Gender categorical
ITT population
Units: Subjects
    Female
15 15
    Male
15 15
Race
ITT population
Units: Subjects
    Caucasian
30 30
Body Mass Index (BMI)
ITT population
Units: kg/m2
    arithmetic mean (standard deviation)
25.51 ± 5.64 -
Longest diameter of the Target Lesions at baseline
Units: cm
    arithmetic mean (standard deviation)
11.46 ± 10.05 -
Urinary 5-HIAA
5-HIAA (5-hydroxyindole acetic acid) N=19
Units: NA
    arithmetic mean (standard deviation)
291.99 ± 462.52 -

End points

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End points reporting groups
Reporting group title
All Subjects
Reporting group description
Lanreotide Autogel 120mg

Primary: Median time to disease progression

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End point title
Median time to disease progression [1]
End point description
Time until disease progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Disease progression was defined as the occurrence, while on treatment with lanreotide Autogel, of one or more new lesions; a ≥20% increase in the sum of the maximum diameters of the “target lesions”, taking as reference the lowest sum of maximum diameters recorded since the start of the study; or unequivocal progression of “nontarget lesions” ITT population
End point type
Primary
End point timeframe
Time between study inclusion until disease progression (Up to Visit 24)
Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Data reported for single arm, due to system limitation, statistical analysis details cannot be reported
End point values
All Subjects
Number of subjects analysed
27
Units: Months
median (confidence interval 95%)
    Progressive Disease
12.9 (7.9 to 16.5)
No statistical analyses for this end point

Secondary: Percentage of reduction of the Serum Chromogranin A as compared to the baseline

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End point title
Percentage of reduction of the Serum Chromogranin A as compared to the baseline
End point description
Patients with Normalised and/or Decrease ≥30% in Serum Chromogranin A (CgA) Concentration at Each Visit ITT population Mc Nemar's Test p values: week 8 (Visit 3) = 0.0002, week 20 (Visit 6) = 0.0027, week 32 (Visit 9) = 0.0082, week 44 (Visit 12) = 0.0253, week 56 (Visit 15) = 0.0253, week 68 (Visit 18) = 0.0455, week 80 (Visit 21) =0.0833 and week 92 (Visit 24) = 0.1573
End point type
Secondary
End point timeframe
At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92
End point values
All Subjects
Number of subjects analysed
30
Units: Percentage of subjects
number (confidence interval 95%)
    At Visit 3
70.4 (53.1 to 87.6)
    At Visit 6
60.9 (40.9 to 80.8)
    At Visit 9
63.2 (41.5 to 84.8)
    At Visit 12
53.3 (28.1 to 78.6)
    At Visit 15
61.5 (35.1 to 88)
    At Visit 18
60 (29.6 to 90.4)
    At Visit 21
57.1 (20.5 to 93.8)
    At Visit 24
66.7 (13.3 to 100)
No statistical analyses for this end point

Secondary: Factors Predictive of Tumour Growth Control for Cox regression

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End point title
Factors Predictive of Tumour Growth Control for Cox regression
End point description
To identify the factors predictive of tumour growth control on treatment with lanreotide Autogel ® ITT population The values reported are Hazard ratio (95% confidence interval) func (functionality) Cox regression p values: Age = 0.8267, Sex = 0.7232, Presence or absence of tumour functionality = 0.0354, ECOG scale = 0.9453, Tumour origin - FOREGUT (REF:UNKNOWN) = 0.0809, Tumour origin - MIDGUT (REF:UNKNOWN) = 0.0323, Tumour origin - MIDGUT (REF:FOREGUT) = 0.4457, Time between tumour diagnosis and study inclusion = 0.2562, Ki-67 index rank = 0.0890, Initial tumour mass = 0.3639, Previous treatment of the tumour: Chemotherapy = 0.9019, Previous treatment of the tumour: Interferon = 0.8273, Previous treatment of the tumour: Radiotherapy = 0.7576, Previous treatment of the tumour: Somatostatin = 0.8946, Previous treatment of the tumour: Surgery = 0.9727, Lanreotide serum levels = 0.7470, CgA response (ref: Yes) = 0.5869
End point type
Secondary
End point timeframe
Duration between study inclusion and the date of the last assessment with a response at “stable disease” (Up to Visit 24)
End point values
All Subjects
Number of subjects analysed
30
Units: Hazard ratio
number (confidence interval 95%)
    Age
0.995 (0.95 to 1.04)
    Sex (ref: MALE)
1.156 (0.52 to 2.59)
    Presence/absence-tumour func (ref: Functional)
2.529 (1.07 to 6)
    ECOG scale
1.03 (0.45 to 2.36)
    Tumour origin - FOREGUT (REF:UNKNOWN)
0.277 (0.07 to 1.17)
    Tumour origin - MIDGUT (REF:UNKNOWN)
0.198 (0.04 to 0.87)
    Tumour origin - MIDGUT (REF:FOREGUT)
0.713 (0.3 to 1.7)
    Time between tumour diagnosis and study inclusion
1 (1 to 1)
    Ki-67 index rank
1.096 (0.99 to 1.22)
    Initial tumour mass
1.019 (0.98 to 1.06)
    Previous treatment of tumour:Chemotherapy(ref:Yes)
1.054 (0.46 to 2.42)
    Previous treatment of tumour: Interferon(ref:Yes)
0.886 (0.3 to 2.64)
    Previous treatment of tumour:Radiotherapy(ref:Yes)
1.375 (0.18 to 10.4)
    Previous treatment of tumour:Somatostatin(ref:Yes)
0.934 (0.34 to 2.55)
    Previous treatment of tumour: Surgery(ref:Yes)
1.016 (0.42 to 2.47)
    Lanreotide serum levels
0.968 (0.79 to 1.18)
    CgA response (ref: Yes)
0.772 (0.3 to 1.96)
No statistical analyses for this end point

Secondary: Factors Predictive of Progression Free Survival for Cox regression

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End point title
Factors Predictive of Progression Free Survival for Cox regression
End point description
To identify the factors predictive of PFS on treatment with lanreotide Autogel ® ITT population The values reported are Hazard ratio (95% confidence interval) func (functionality) Cox regression p values: Age = 0.3669, Sex = 0.4633, Presence or absence of tumour functionality = 0.1214, ECOG scale = 0.1961, Time between tumour diagnosis and study inclusion = 0.3968, Ki-67 index rank = 0.0178, Initial tumour mass = 0.9933, Previous treatment of the tumour: Chemotherapy = 0.3175, Previous treatment of the tumour: Interferon = 0.7742, Previous treatment of the tumour: Radiotherapy = 0.7733, Previous treatment of the tumour: Somatostatin = 0.8288, Previous treatment of the tumour: Surgery = 0.9416, Lanreotide serum levels = 0.5550, CgA response (ref: Yes) = 0.9959, Tumour origin - FOREGUT (REF:UNKNOWN) = 0.1457, Tumour origin - MIDGUT (REF:UNKNOWN) = 0.0694, Tumour origin - MIDGUT (REF:FOREGUT) = 0.5111
End point type
Secondary
End point timeframe
Duration between study inclusion and the date of disease progression (Up to Visit 24)
End point values
All Subjects
Number of subjects analysed
30
Units: Hazard ratio
number (confidence interval 95%)
    Age
0.981 (0.94 to 1.02)
    Sex (ref: MALE)
0.718 (0.3 to 1.74)
    Presence/absence of tumour func(ref: Functional)
2.036 (0.83 to 5.01)
    ECOG scale
1.659 (0.77 to 3.57)
    Tumour origin - FOREGUT (REF:UNKNOWN)
0.352 (0.09 to 1.44)
    Tumour origin - MIDGUT (REF:UNKNOWN)
0.257 (0.06 to 1.11)
    Tumour origin - MIDGUT (REF:FOREGUT)
0.73 (0.29 to 1.87)
    Time between tumour diagnosis and study inclusion
1 (1 to 1)
    Ki-67 index rank
1.17 (1.03 to 1.33)
    Initial tumour mass
1 (0.95 to 1.05)
    Previous treatment tumour:Chemotherapy (ref: Yes)
1.623 (0.63 to 4.2)
    Previous treatment tumour:Interferon (ref: Yes)
0.852 (0.29 to 2.54)
    Previous treatment tumour:Radiotherapy (ref:Yes)
1.347 (0.18 to 10.2)
    Previous treatment tumour:Somatostatin (ref:Yes)
0.886 (0.3 to 2.64)
    Previous treatment tumour:Surgery (ref:Yes)
0.965 (0.37 to 2.49)
    Lanreotide serum levels
0.933 (0.74 to 1.18)
    CgA response (ref: Yes)
1.003 (0.38 to 2.63)
No statistical analyses for this end point

Secondary: Number of subjects with Partial or Complete Response of the Tumoural Lesions

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End point title
Number of subjects with Partial or Complete Response of the Tumoural Lesions
End point description
ITT population Complete response (CR): Disappearance of all “target lesions” and “nontarget lesions”, and normalisation of tumour marker concentrations. Partial response (PR): A reduction of at least 30% of the sum of maximum diameters of the “target lesions” taking as reference the baseline maximum diameters, and/or disappearance of all the “target lesions” with persistence of one or more “nontarget lesions” and/or tumour markers over the limits of the disease.
End point type
Secondary
End point timeframe
Up to Visit 24 (Week 92)
End point values
All Subjects
Number of subjects analysed
30
Units: Number of subjects
    Partial Response
0
    Complete Response
0
No statistical analyses for this end point

Secondary: Mean Change from Baseline of sum of the Longest Diameter of the target lesions

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End point title
Mean Change from Baseline of sum of the Longest Diameter of the target lesions
End point description
ITT population
End point type
Secondary
End point timeframe
At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92
End point values
All Subjects
Number of subjects analysed
30
Units: cm
arithmetic mean (standard deviation)
    Week 8 (N=27)
0.14 ± 1.06
    Week 20 (n=23)
0.34 ± 2.02
    Week 32 (N=19)
-0.25 ± 1.36
    Week 44 (N=15)
-0.19 ± 1.9
    Week 56 (N=12)
-0.31 ± 0.78
    week 68 (N=11)
-0.17 ± 0.52
    Week 80 (N=7)
0.6 ± 1.31
    Week 92 (N=3)
-0.2 ± 0.17
No statistical analyses for this end point

Secondary: Mean change from Baseline of Maximum Decrease or Minimum Increase of the Longest Diameter of the target lesions

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End point title
Mean change from Baseline of Maximum Decrease or Minimum Increase of the Longest Diameter of the target lesions
End point description
ITT population
End point type
Secondary
End point timeframe
At Baseline (Visit 0) and week 92 (visit 24)
End point values
All Subjects
Number of subjects analysed
27
Units: cm
arithmetic mean (standard deviation)
    MAXIMUM DECREASE OR MINIMUM INCREASE FROM BASELINE
-0.35 ± 1.58
No statistical analyses for this end point

Secondary: Mean Percentage Change from Baseline of Other Tumour Markers: Urinary 5-HIAA

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End point title
Mean Percentage Change from Baseline of Other Tumour Markers: Urinary 5-HIAA
End point description
ITT population 5-HIAA (5- hydroxyindole acetic acid) Student's test values: week 8 (Visit 3) = 0.0006, week 20 (Visit 6) = 0.0005, week 56 (Visit 15) = 0.0220, week 68 (Visit 18) = 0.5820; Wilcoxon's test values: week 32 (Visit 9) = 0.4697, week 44 (Visit 12) = 0.3223; Within-group test Not done at week 80 (Visit 21) and week 92 (Visit 24)
End point type
Secondary
End point timeframe
At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92
End point values
All Subjects
Number of subjects analysed
30
Units: Percentage change
arithmetic mean (standard deviation)
    Week 8 (N=17)
-30.1 ± 29.3
    Week 20 (N=12)
-33.8 ± 24.4
    Week 32 (N=12)
-9.6 ± 66.9
    Week 44 (N=10)
-11.4 ± 63.1
    Week 56 (N=8)
-36.6 ± 35.3
    week 68 (N=8)
-10.9 ± 53.5
    Week 80 (N=6)
-34.8 ± 46.9
    Week 92 (N=3)
-62.9 ± 16.7
No statistical analyses for this end point

Secondary: Baseline Mean And Change in Mean of QLQ-C30 by Five Functional Scale

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End point title
Baseline Mean And Change in Mean of QLQ-C30 by Five Functional Scale
End point description
The QLQ-C30 is composed of both multi-item scales and single item measures. These include five functional scales (physical [PF], role [RF], emotional [EF], cognitive [CF] and social [SF]) QLQ-C30 (Quality of Life Questionnaire) ITT population
End point type
Secondary
End point timeframe
At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92
End point values
All Subjects
Number of subjects analysed
30
Units: Units on a scale
arithmetic mean (standard deviation)
    Physical Functioning: Baseline (N=27)
90.37 ± 12.59
    Physical Functioning: Week 8 (N=15)
-4.22 ± 15.14
    Physical Functioning: Week 20 (N=15)
-8.89 ± 22.35
    Physical Functioning: Week 32 (N=11)
0.61 ± 3.6
    Physical Functioning: Week 44 (N=9)
0.74 ± 5.21
    Physical Functioning: Week 56 (N=8)
4.17 ± 7.07
    Physical Functioning: Week 68 (N=8)
0.83 ± 6.61
    Physical Functioning: Week 80 (N=3)
-8.89 ± 15.4
    Physical Functioning: Week 92 (N=1)
0 ± 0
    Role Functioning: Baseline (N=27)
87.04 ± 21.35
    Role Functioning: Week 8 (N=15)
1.11 ± 14.73
    Role Functioning: Week 20 (N=15)
2.22 ± 12.39
    Role Functioning: Week 32 (N=11)
6.06 ± 15.41
    Role Functioning: Week 44 (N=9)
5.56 ± 16.67
    Role Functioning: Week 56 (N=8)
2.08 ± 5.89
    Role Functioning: Week 68 (N=8)
-6.25 ± 12.4
    Role Functioning: Week 80 (N=3)
-22.22 ± 38.49
    Role Functioning: Week 92 (N=1)
0 ± 0
    Cognitive Functioning: Baseline (N=28)
84.52 ± 22.19
    Cognitive Functioning: Week 8 (N=16)
3.13 ± 23.74
    Cognitive Functioning: Week 20 (N=16)
-6.25 ± 17.08
    Cognitive Functioning: Week 32 (N=11)
0 ± 16.67
    Cognitive Functioning: Week 44 (N=10)
1.67 ± 18.34
    Cognitive Functioning: Week 56 (N=9)
1.85 ± 26.93
    Cognitive Functioning: Week 68 (N=9)
7.41 ± 23.73
    Cognitive Functioning: Week 80 (N=4)
8.33 ± 28.87
    Cognitive Functioning: Week 92 (N=1)
0 ± 0
    Emotional Functioning: Baseline (N=28)
72.02 ± 26.47
    Emotional Functioning: Week 8 (N=16)
4.69 ± 21.29
    Emotional Functioning: Week 20 (N=16)
3.65 ± 28.86
    Emotional Functioning: Week 32 (N=11)
3.03 ± 15.49
    Emotional Functioning: Week 44 (N=10)
8.33 ± 23.57
    Emotional Functioning: Week 56 (N=9)
11.11 ± 17.68
    Emotional Functioning: Week 68 (N=9)
1.85 ± 35.79
    Emotional Functioning: Week 80 (N=4)
22.92 ± 29.17
    Emotional Functioning: Week 92 (N=1)
8.33 ± 0
    Social Functioning: Baseline (N=28)
90.48 ± 17.23
    Social Functioning: Week 8 (N=16)
-1.04 ± 21.49
    Social Functioning: Week 20 (N=16)
0 ± 20.18
    Social Functioning: Week 32 (N=11)
-7.58 ± 20.23
    Social Functioning: Week 44 (N=10)
-10 ± 14.05
    Social Functioning: Week 56 (N=9)
-5.56 ± 20.41
    Social Functioning: Week 68 (N=9)
-7.41 ± 26.5
    Social Functioning: Week 80 (N=4)
4.17 ± 20.97
    Social Functioning: Week 92 (N=1)
0 ± 0
No statistical analyses for this end point

Secondary: Baseline Mean And Change in Mean of QLQ-C30 Three Symptom Scale

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End point title
Baseline Mean And Change in Mean of QLQ-C30 Three Symptom Scale
End point description
The QLQ-C30 is composed of both multi-item scales and single item measures. These include three symptom scales (fatigue [FA], nausea and vomiting[NV], and pain [PA]). QLQ-C30 (Quality of Life Questionnaire) ITT population
End point type
Secondary
End point timeframe
At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92
End point values
All Subjects
Number of subjects analysed
30
Units: Units on a scale
arithmetic mean (standard deviation)
    Fatigue: Baseline (N=27)
16.46 ± 19.09
    Fatigue: Week 8 (N=15)
5.93 ± 17.75
    Fatigue: Week 20 (N=15)
2.96 ± 17.04
    Fatigue: Week 32 (N=11)
5.05 ± 12.54
    Fatigue: Week 44 (N=9)
6.17 ± 14.81
    Fatigue: Week 56 (N=8)
-2.78 ± 23.57
    Fatigue: Week 68 (N=8)
19.44 ± 27.7
    Fatigue: Week 80 (N=3)
7.41 ± 12.83
    Fatigue: Week 92 (N=1)
0 ± 0
    Nausea And Vomiting: Baseline (N=28)
9.52 ± 20.5
    Nausea And Vomiting: Week 8 (N=16)
-6.25 ± 17.08
    Nausea And Vomiting: Week 20 (N=16)
-3.13 ± 12.5
    Nausea And Vomiting: Week 32 (N=11)
0 ± 0
    Nausea And Vomiting: Week 44 (N=10)
0 ± 0
    Nausea And Vomiting: Week 56 (N=9)
-5.56 ± 23.57
    Nausea And Vomiting: Week 68 (N=9)
-7.41 ± 22.22
    Nausea And Vomiting: Week 80 (N=4)
-16.67 ± 33.33
    Nausea And Vomiting: Week 92 (N=1)
0 ± 0
    Pain Scale: Baseline (N=28)
20.24 ± 26.59
    Pain Scale: Week 8 (N=16)
6.25 ± 30.35
    Pain Scale: Week 20 (N=16)
2.08 ± 17.08
    Pain Scale: Week 32 (N=11)
0 ± 16.67
    Pain Scale: Week 44 (N=10)
8.33 ± 25.15
    Pain Scale: Week 56 (N=9)
-5.56 ± 22.05
    Pain Scale: Week 68 (N=9)
3.7 ± 34.13
    Pain Scale: Week 80 (N=4)
-16.67 ± 30.43
    Pain Scale: Week 92 (N=1)
-33.33 ± 0
No statistical analyses for this end point

Secondary: Baseline Mean And Change in Mean of QLQ-C30 Six Single Scale

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End point title
Baseline Mean And Change in Mean of QLQ-C30 Six Single Scale
End point description
The QLQ-C30 is composed of both multi-item scales and single item measures. These include six single items (dyspnoea [DY], insomnia/sleep disturbance [SL], appetite loss [AP], constipation [CO], diarrhoea [DI] and financial difficulties [FI]). QLQ-C30 (Quality of Life Questionnaire) ITT population
End point type
Secondary
End point timeframe
At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92
End point values
All Subjects
Number of subjects analysed
30
Units: Units on a scale
arithmetic mean (standard deviation)
    Dyspnoea: Baseline (N=27)
1.23 ± 6.42
    Dyspnoea: Week 8 (N=15)
4.44 ± 11.73
    Dyspnoea: Week 20 (N=15)
4.44 ± 11.73
    Dyspnoea: Week 32 (N=11)
3.03 ± 10.05
    Dyspnoea: Week 44 (N=9)
0 ± 0
    Dyspnoea: Week 56 (N=8)
0 ± 0
    Dyspnoea: Week 68 (N=8)
0 ± 0
    Dyspnoea: Week 80 (N=3)
22.22 ± 38.49
    Dyspnoea: Week 92 (N=1)
0 ± 0
    Insomnia: Baseline (N=27)
25.93 ± 33.76
    Insomnia: Week 8 (N=15)
6.67 ± 18.69
    Insomnia: Week 20 (N=15)
-2.22 ± 23.46
    Insomnia: Week 32 (N=11)
0 ± 29.81
    Insomnia: Week 44 (N=9)
11.11 ± 16.67
    Insomnia: Week 56 (N=8)
16.67 ± 25.2
    Insomnia: Week 68 (N=8)
16.67 ± 30.86
    Insomnia: Week 80 (N=3)
0 ± 0
    Insomnia: Week 92 (N=1)
0 ± 0
    Appetite Loss: Baseline (N=27)
8.64 ± 19.81
    Appetite Loss: Week 8 (N=15)
11.11 ± 24.12
    Appetite Loss: Week 20 (N=15)
8.89 ± 19.79
    Appetite Loss: Week 32 (N=11)
3.03 ± 10.05
    Appetite Loss: Week 44 (N=9)
7.41 ± 22.22
    Appetite Loss: Week 56 (N=8)
-4.17 ± 11.79
    Appetite Loss: Week 68 (N=8)
8.33 ± 29.55
    Appetite Loss: Week 80 (N=3)
-11.11 ± 19.25
    Appetite Loss: Week 92 (N=1)
0 ± 0
    Cosntipation Scale: Baseline (N=28)
9.52 ± 19.99
    Cosntipation Scale: Week 8 (N=16)
12.5 ± 36.26
    Cosntipation Scale: Week 20 (N=16)
6.25 ± 13.44
    Cosntipation Scale: Week 32 (N=11)
-6.06 ± 13.48
    Cosntipation Scale: Week 44 (N=10)
-6.67 ± 14.05
    Cosntipation Scale: Week 56 (N=9)
-3.7 ± 20.03
    Cosntipation Scale: Week 68 (N=9)
-11.11 ± 23.57
    Cosntipation Scale: Week 80 (N=4)
-16.67 ± 33.33
    Cosntipation Scale: Week 92 (N=1)
33.33 ± 0
    Diarrhoea Scale: Baseline (N=28)
27.38 ± 30.16
    Diarrhoea Scale: Week 8 (N=16)
-10.42 ± 20.07
    Diarrhoea Scale: Week 20 (N=16)
-6.25 ± 38.91
    Diarrhoea Scale: Week 32 (N=11)
-6.06 ± 29.13
    Diarrhoea Scale: Week 44 (N=10)
-3.33 ± 18.92
    Diarrhoea Scale: Week 56 (N=9)
-7.41 ± 22.22
    Diarrhoea Scale: Week 68 (N=9)
7.41 ± 22.22
    Diarrhoea Scale: Week 80 (N=4)
0 ± 38.49
    Diarrhoea Scale: Week 92 (N=1)
33.33 ± 0
    Financial Difficulties: Baseline (N=28)
8.33 ± 23.35
    Financial Difficulties: Week 8 (N=16)
-2.08 ± 30.96
    Financial Difficulties: Week 20 (N=16)
-10.42 ± 26.44
    Financial Difficulties: Week 32 (N=11)
0 ± 0
    Financial Difficulties: Week 44 (N=10)
3.33 ± 18.92
    Financial Difficulties: Week 56 (N=9)
0 ± 28.87
    Financial Difficulties: Week 68 (N=9)
11.11 ± 37.27
    Financial Difficulties: Week 80 (N=4)
16.67 ± 33.33
    Financial Difficulties: Week 92 (N=1)
0 ± 0
No statistical analyses for this end point

Secondary: Baseline Mean And Change in Mean of QLQ-C30 Global Quality Of Life Scale

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End point title
Baseline Mean And Change in Mean of QLQ-C30 Global Quality Of Life Scale
End point description
The QLQ-C30 is composed of both multi-item scales and single item measures. ITT population
End point type
Secondary
End point timeframe
At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92
End point values
All Subjects
Number of subjects analysed
30
Units: Units on a scale
arithmetic mean (standard deviation)
    Global Health Status: Baseline (N=28)
69.05 ± 22.32
    Global Health Status: Week 8 (N=16)
1.56 ± 18.06
    Global Health Status: Week 20 (N=16)
2.6 ± 22.92
    Global Health Status: Week 32 (N=11)
-4.55 ± 19.49
    Global Health Status: Week 44 (N=10)
2.5 ± 15.24
    Global Health Status: Week 56 (N=9)
8.33 ± 17.18
    Global Health Status: Week 68 (N=9)
-19.44 ± 26.68
    Global Health Status: Week 80 (N=4)
6.25 ± 14.23
    Global Health Status: Week 92 (N=1)
0 ± 0
No statistical analyses for this end point

Secondary: Number of Subjects With Symptomatic Control related to Neuroendocrine Tumours During The Treatment Period

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End point title
Number of Subjects With Symptomatic Control related to Neuroendocrine Tumours During The Treatment Period
End point description
Evaluation of the symptom control ITT population NET (Neuroendocrine tumours)
End point type
Secondary
End point timeframe
Up to Visit 24 (Week 92)
End point values
All Subjects
Number of subjects analysed
30
Units: Number of subjects
    Symptoms related to NET
6
    Diarrhoea
6
    Asthenia
1
    Flushes
1
    Suffocations with tachycardia
1
No statistical analyses for this end point

Adverse events

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Adverse events information
Timeframe for reporting adverse events
Up to visit 24
Assessment type
Systematic
Dictionary used for adverse event reporting
Dictionary name
MedDRA
Dictionary version
11.1
Reporting groups
Reporting group title
All Subjects
Reporting group description
Safety population: includes all patients who have received at least one dose of Somatuline Autogel® (same definition as ITT population)

Serious adverse events
All Subjects
Total subjects affected by serious adverse events
     subjects affected / exposed
6 / 30 (20.00%)
     number of deaths (all causes)
2
     number of deaths resulting from adverse events
2
Injury, poisoning and procedural complications
Ankle fracture
     subjects affected / exposed
1 / 30 (3.33%)
     occurrences causally related to treatment / all
0 / 1
     deaths causally related to treatment / all
0 / 0
Gastrointestinal disorders
Intestinal obstruction
     subjects affected / exposed
3 / 30 (10.00%)
     occurrences causally related to treatment / all
0 / 3
     deaths causally related to treatment / all
1 / 1
Renal and urinary disorders
Renal failure acute
     subjects affected / exposed
1 / 30 (3.33%)
     occurrences causally related to treatment / all
1 / 1
     deaths causally related to treatment / all
0 / 0
Hepatobiliary disorders
Gallbladder fistula
     subjects affected / exposed
1 / 30 (3.33%)
     occurrences causally related to treatment / all
0 / 1
     deaths causally related to treatment / all
1 / 1
Skin and subcutaneous tissue disorders
Skin ulcer
     subjects affected / exposed
1 / 30 (3.33%)
     occurrences causally related to treatment / all
0 / 1
     deaths causally related to treatment / all
0 / 0
Infections and infestations
Appendicitis
     subjects affected / exposed
1 / 30 (3.33%)
     occurrences causally related to treatment / all
0 / 1
     deaths causally related to treatment / all
0 / 0
Frequency threshold for reporting non-serious adverse events: 5%
Non-serious adverse events
All Subjects
Total subjects affected by non serious adverse events
     subjects affected / exposed
25 / 30 (83.33%)
Blood and lymphatic system disorders
Anaemia
     subjects affected / exposed
2 / 30 (6.67%)
     occurrences all number
4
Nervous system disorders
Dizziness
     subjects affected / exposed
3 / 30 (10.00%)
     occurrences all number
7
General disorders and administration site conditions
Asthenia
     subjects affected / exposed
8 / 30 (26.67%)
     occurrences all number
20
Injection site pain
     subjects affected / exposed
3 / 30 (10.00%)
     occurrences all number
8
Injection site nodule
     subjects affected / exposed
2 / 30 (6.67%)
     occurrences all number
2
Psychiatric disorders
Anxiety
     subjects affected / exposed
3 / 30 (10.00%)
     occurrences all number
6
Gastrointestinal disorders
Diarrhoea
     subjects affected / exposed
13 / 30 (43.33%)
     occurrences all number
30
Abdominal pain
     subjects affected / exposed
4 / 30 (13.33%)
     occurrences all number
7
Flatulence
     subjects affected / exposed
3 / 30 (10.00%)
     occurrences all number
3
Constipation
     subjects affected / exposed
2 / 30 (6.67%)
     occurrences all number
3
Vomiting
     subjects affected / exposed
2 / 30 (6.67%)
     occurrences all number
2
Skin and subcutaneous tissue disorders
Pruritus
     subjects affected / exposed
2 / 30 (6.67%)
     occurrences all number
3
Musculoskeletal and connective tissue disorders
Back pain
     subjects affected / exposed
3 / 30 (10.00%)
     occurrences all number
3
Arthralgia
     subjects affected / exposed
2 / 30 (6.67%)
     occurrences all number
2
Metabolism and nutrition disorders
Hyperglycaemia
     subjects affected / exposed
3 / 30 (10.00%)
     occurrences all number
5
Infections and infestations
Nasopharyngitis
     subjects affected / exposed
4 / 30 (13.33%)
     occurrences all number
4

More information

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Substantial protocol amendments (globally)

Were there any global substantial amendments to the protocol? Yes
Date
Amendment
23 Feb 2006
Two new centers has been incorporated. To do faster the procedure to assign randomization codes to radiological copies.

Interruptions (globally)

Were there any global interruptions to the trial? No

Limitations and caveats

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported