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Trial record 14 of 34 for:    Lanreotide | Neuroendocrine Tumors

Combination of Lanreotide Autogel 120mg and Temozolomide in Progressive GEP-NET (SONNET)

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ClinicalTrials.gov Identifier: NCT02231762
Recruitment Status : Completed
First Posted : September 4, 2014
Results First Posted : May 6, 2019
Last Update Posted : May 6, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Gastroenteropancreatic Neuroendocrine Tumors
Interventions Drug: Lanreotide Autogel 120 mg
Drug: Temozolomide (TMZ)
Enrollment 57
Recruitment Details 57 subjects entered a combination phase and received lanreotide ATG 120 mg plus temozolomide for 6 months. A 6 month maintenance phase then followed where subjects received either lanreotide ATG 120 mg or no treatment, dependent upon whether they had functioning or non-functioning NET, clinical benefit and allocation following randomisation.
Pre-assignment Details Overall, 64 subjects were screened, 7 were screening failures of which 5 subjects did not meet the entry criteria. 57 subjects were assigned to receive treatment in the baseline population.
Arm/Group Title Combination Phase Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Hide Arm/Group Description

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6.

In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24.
Period Title: Combination Phase
Started 57 0 [1] 0 [1] 0 [1]
Completed 37 0 0 0
Not Completed 20 0 0 0
Reason Not Completed
Adverse Event             10             0             0             0
Withdrawal by Subject             2             0             0             0
Disease Progression             6             0             0             0
Did not meet inclusion criteria             1             0             0             0
Protocol Violation             1             0             0             0
[1]
This arm was not included in period 1 (combination phase).
Period Title: Maintenance Phase
Started 0 [1] 11 [2] 14 [2] 12 [2]
Completed 0 8 9 7
Not Completed 0 3 5 5
Reason Not Completed
Disease progression             0             3             4             3
Adverse Event             0             0             1             2
[1]
This arm was not included in period 2 (maintenance phase).
[2]
The 37 subjects completing period 1 were split between the 3 arms in period 2.
Arm/Group Title Combination Phase
Hide Arm/Group Description

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6.

Overall Number of Baseline Participants 57
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 57 participants
63.1  (11.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants
Female
24
  42.1%
Male
33
  57.9%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 57 participants
American Indian or Alaska Native.
0
   0.0%
Asian.
0
   0.0%
Black or African American
0
   0.0%
Hispanic or Latino
0
   0.0%
Native Hawaiian or Other Pacific Islander.
0
   0.0%
White
57
 100.0%
1.Primary Outcome
Title Disease Control Rate (DCR) After 6 Months
Hide Description

All tumour assessments were performed using the Response Evaluation Criteria In Solid Tumours (RECIST) criteria (1.1). Computer Tomography (CT-scan) or Magnetic Resonance Imaging (MRI) could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at weeks 12, 24 and at early withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression.

The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment and was described in the ITT population along with its 95% Confidence Interval (CI) and was compared to 45% with an exact binomial proportion test. The Last Observation Carried Forward (LOCF) method was used to replace missing assessments at the end of the combination phase.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is all subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
Arm/Group Title Combination Phase
Hide Arm/Group Description:

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6.

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
73.5
(58.9 to 85.1)
2.Secondary Outcome
Title DCR After 12 Months
Hide Description

All tumour assessments were performed using the RECIST criteria (1.1). CT-scan or MRI could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at baseline, weeks 12, 24, 36, 48 (end of study) and at study withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression.

The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months combination treatment followed by either 6 months of lanreotide ATG 120 mg maintenance treatment or no treatment. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test. The LOCF method was used to replace missing assessments at the end of the maintenance phase.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is all subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
Arm/Group Title Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Hide Arm/Group Description:
In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24.
Overall Number of Participants Analyzed 11 14 12
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
54.5
(23.4 to 83.3)
71.4
(41.9 to 91.6)
41.7
(15.2 to 72.3)
3.Secondary Outcome
Title Progression–Free Survival (PFS) Within 12 Months
Hide Description

PFS was defined as the time from the date of treatment start to the date of the first documented disease progression or death due to any cause within the first 12 months of treatment. If a subject had not progressed or died after 12 months of treatment or when any further anti-neoplastic therapy was received, PFS was censored at the time of the last tumour assessment before the analysis cut-off date or the anti-neoplastic therapy date.

A Kaplan-Meier estimate of the PFS was calculated to determine the number of subjects at risk. Median PFS time (50% of subjects who would not progress or die) of the ITT population is presented along with 95 % CI.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is all treated subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
Arm/Group Title Intention-to-treat (ITT) Population
Hide Arm/Group Description:
All treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
Overall Number of Participants Analyzed 49
Median (95% Confidence Interval)
Unit of Measure: months
11.1 [1] 
(8.3 to NA)
[1]
Upper limit of the 95 % CI could not be determined as too few survival events for complete data estimation were observed during the 12 month study duration.
4.Secondary Outcome
Title Time To Response (TtR) Within 12 Months
Hide Description

TtR was defined as the time from the date of treatment start to the date of the first documented objective response (CR or PR) within the first 12 months of treatment (combination and maintenance phases). A Kaplan Meier estimate of the TtR survival function was constructed.

The Kaplan-Meier method was used to estimate the median TtR and its 95% CI for subjects in the ITT population (50% of subjects were expected to have a CR or PR at this time).

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is all treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter
Arm/Group Title Intention-to-treat (ITT) Population
Hide Arm/Group Description:
All treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
Overall Number of Participants Analyzed 49
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
[1]
The results could not be determined as too few subjects recorded a response event during the 12 month study duration.
5.Secondary Outcome
Title Duration of Response (DoR) Within 12 Months
Hide Description

The DoR is an estimation of the time from first documented objective response (CR or PR) to the first date of progressive disease (PD) or death due to disease progression for subjects who experienced an objective response within the first 12 months of treatment (combination and maintenance phases).

The Kaplan-Meier method was used to estimate the median DoR and its 95% CI for subjects in the ITT population who had an objective response.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population is all treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
Arm/Group Title Intention-to-treat (ITT) Population
Hide Arm/Group Description:
All treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
Overall Number of Participants Analyzed 6
Median (95% Confidence Interval)
Unit of Measure: months
NA [1] 
(NA to NA)
[1]
The results could not be determined as too few subjects recorded a response event during the 12 month study duration.
6.Secondary Outcome
Title The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months
Hide Description

Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24 and at early withdrawal. The biochemical response after 6 months combination treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 micrograms/litre [mcg/L]).

Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥ 50%, compared to the baseline CgA), SD (decrease < 50 % or an increase ≤25%, compared to the baseline CgA) or PD (defined as an increase ≥25 %, compared to the baseline CgA).

The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the ITT population with abnormal CgA levels at baseline.
Arm/Group Title Combination Phase
Hide Arm/Group Description:

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6.

Overall Number of Participants Analyzed 34
Measure Type: Count of Participants
Unit of Measure: Participants
Week 12- PD 8
Week 12 - SD 15
Week 12- PR 10
Week 12 - Missing 1
Week 24 - PD 5
Week 24 - SD 9
Week 24 - PR 7
Week 24 - Missing 0
Early Withdrawal - PD 1
Early Withdrawal - SD 2
Early Withdrawal - PR 1
Early Withdrawal - Missing 14
7.Secondary Outcome
Title The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months
Hide Description

Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and at early withdrawal. The biochemical response after 12 months combination and maintenance treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 mcg/L).

Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥50 % compared to the baseline CgA), SD (decrease < 50% or an increase ≤ 25% compared to the baseline CgA) or PD (defined as an increase ≥ 25%, compared to the baseline CgA).

The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the ITT population with abnormal CgA levels at baseline.
Arm/Group Title Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Hide Arm/Group Description:
In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24.
Overall Number of Participants Analyzed 5 9 9
Measure Type: Count of Participants
Unit of Measure: Participants
Week 24 - PD 2 1 2
Week 24 - SD 3 4 2
Week 24 - PR 0 3 3
Week 24 - Missing 0 1 2
Week 36 - PD 1 1 3
Week 36 - SD 2 4 2
Week 36 - PR 0 1 4
Week 36 - Missing 0 1 0
Week 48 - PD 1 1 2
Week 48 - SD 0 2 3
Week 48 - PR 1 2 1
Week 48 - Missing 0 0 0
Early Withdrawal - PD 1 2 1
Early Withdrawal - SD 0 0 0
Early Withdrawal - PR 0 1 1
Early Withdrawal - Missing 2 0 0
8.Secondary Outcome
Title The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months
Hide Description

Urine samples for 5-HIAA urinary tumour marker analysis were taken at at baseline, weeks 12, 24and early withdrawal.

Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline).

The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the ITT population with functioning NET.
Arm/Group Title Combination Phase - Functioning NET
Hide Arm/Group Description:
All subjects in the combination phase who were categorised at baseline as having functioning NET.
Overall Number of Participants Analyzed 17
Measure Type: Count of Participants
Unit of Measure: Participants
Week 12 - Progression 4
Week 12 - Response 6
Week 12 - Not evaluable 1
Week 12 - Missing 6
Week 24 - Progression 6
Week 24 - Response 3
Week 24 - Not evaluable 1
Week 24 - Missing 3
Early Withdrawal - Progression 0
Early Withdrawal - Response 1
Early Withdrawal - Not Evaluable 0
Early Withdrawal - Missing 7
9.Secondary Outcome
Title The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months
Hide Description

Urine samples for 5-HIAA urinary tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and early withdrawal.

Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline).

The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the ITT population with functioning NET.
Arm/Group Title Maintenance Phase - Functioning NET, Lanreotide
Hide Arm/Group Description:
In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
Overall Number of Participants Analyzed 11
Measure Type: Count of Participants
Unit of Measure: Participants
Week 24 - Progression 6
Week 24 - Response 3
Week 24 - Not evaluable 1
Week 24 - Missing 1
Week 36 - Progression 3
Week 36 - Response 3
Week 36 - Not evaluable 0
Week 36 - Missing 3
Week 48 - Progression 4
Week 48 - Response 2
Week 48 - Not evaluable 0
Week 48 - Missing 2
Early Withdrawal - Progression 0
Early Withdrawal - Response 0
Early Withdrawal - Not evaluable 0
Early Withdrawal - Missing 3
10.Secondary Outcome
Title The Number of Subjects With a Symptomatic Response After 6 Months
Hide Description

Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline.

Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing.

The number of subjects in each response category at week 24 (end of the combination phase) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the ITT population with functioning NET.
Arm/Group Title Combination Phase - Functioning NET
Hide Arm/Group Description:
All subjects in the combination phase who were categorised at baseline as having functioning NET.
Overall Number of Participants Analyzed 17
Measure Type: Count of Participants
Unit of Measure: Participants
Diarrhoea - Reduction 4
Diarrhoea - Increase 2
Diarrhoea - Stability 5
Diarrhoea - Missing 6
Flushing - Reduction 4
Flushing - Increase 4
Flushing - Stability 3
Flushing - Missing 6
11.Secondary Outcome
Title The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase
Hide Description

Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline.

Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing.

The number of subjects in each response category at week 48 (end of study) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.

Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects in the ITT population with functioning NET.
Arm/Group Title Maintenance Phase - Functioning NET, Lanreotide
Hide Arm/Group Description:
In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
Overall Number of Participants Analyzed 11
Measure Type: Count of Participants
Unit of Measure: Participants
Diarrhoea - Reduction 4
Diarrhoea - Increase 1
Diarrhoea - Stability 3
Diarrhoea - Missing 3
Flushing - Reduction 2
Flushing - Increase 3
Flushing - Stability 3
Flushing - Missing 3
12.Secondary Outcome
Title European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months
Hide Description Subjects were instructed to complete the QLQ-C30 questionnaire at baseline, weeks 12, 24 or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 24 (end of the combination phase) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only subjects in the ITT Population with data available at the week 24 time point were analysed. Only subjects with data available for analysis are presented.
Arm/Group Title Combination Phase
Hide Arm/Group Description:

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6.

Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: units on a scale
Global health status Number Analyzed 34 participants
-4.9  (18.2)
Physical functioning Number Analyzed 34 participants
-9.6  (19.4)
Role functioning Number Analyzed 34 participants
-8.3  (27.6)
Emotional functioning Number Analyzed 34 participants
-4.7  (17.7)
Cognitive functioning Number Analyzed 34 participants
-5.9  (15.8)
Social functioning Number Analyzed 34 participants
-11.8  (23.8)
Fatigue Number Analyzed 34 participants
6.9  (20.1)
Nausea and vomiting Number Analyzed 34 participants
6.9  (14.9)
Pain Number Analyzed 34 participants
-1.0  (31.0)
Dyspnoea Number Analyzed 34 participants
12.7  (30.7)
Insomnia Number Analyzed 32 participants
0.0  (34.9)
Appetite loss Number Analyzed 34 participants
2.0  (24.5)
Constipation Number Analyzed 34 participants
6.9  (33.6)
Diarrhoea Number Analyzed 34 participants
-3.9  (34.6)
Financial difficulties Number Analyzed 34 participants
2.9  (17.1)
13.Secondary Outcome
Title EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months
Hide Description Subjects were instructed to complete QLQ-C30 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 48 (end of study) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only subjects in the ITT Population with data available at the week 48 time point were analysed. Only subjects with data available for analysis are presented.
Arm/Group Title Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Hide Arm/Group Description:
In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24.
Overall Number of Participants Analyzed 5 8 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
Global health status Number Analyzed 5 participants 8 participants 7 participants
-11.7  (40.7) -3.1  (10.9) -7.1  (15.5)
Physical functioning Number Analyzed 5 participants 8 participants 7 participants
8.0  (22.8) -12.5  (17.6) -11.4  (13.7)
Role functioning Number Analyzed 5 participants 8 participants 7 participants
3.3  (29.8) -2.1  (20.8) -7.1  (13.1)
Emotional functioning Number Analyzed 5 participants 8 participants 7 participants
15.0  (19.0) -6.2  (20.3) -6.0  (12.5)
Cognitive functioning Number Analyzed 5 participants 8 participants 7 participants
3.3  (24.7) -2.1  (20.8) 2.4  (6.3)
Social functioning Number Analyzed 5 participants 8 participants 7 participants
13.3  (34.2) -22.9  (34.4) -4.8  (15.9)
Fatigue Number Analyzed 5 participants 8 participants 7 participants
-22.2  (30.4) -9.7  (24.1) 4.8  (16.8)
Nausea and vomiting Number Analyzed 5 participants 8 participants 7 participants
-10.0  (14.9) 4.2  (23.1) 2.4  (6.3)
Pain Number Analyzed 5 participants 8 participants 7 participants
-13.3  (32.1) 4.2  (24.8) 9.5  (23.3)
Dyspnoea Number Analyzed 4 participants 8 participants 7 participants
-8.3  (41.9) 4.2  (33.0) 9.5  (16.3)
Insomnia Number Analyzed 5 participants 8 participants 6 participants
-13.3  (50.6) -8.3  (34.5) 16.7  (27.9)
Appetite loss Number Analyzed 5 participants 8 participants 7 participants
0.0  (23.6) 0.0  (39.8) 14.3  (17.8)
Constipation Number Analyzed 5 participants 8 participants 7 participants
20.0  (38.0) -4.2  (11.8) -4.8  (35.6)
Diarrhoea Number Analyzed 5 participants 8 participants 7 participants
-40.0  (36.5) 8.3  (15.4) 0.0  (27.2)
Financial difficulties Number Analyzed 5 participants 8 participants 7 participants
6.7  (14.9) 4.2  (27.8) 9.5  (25.2)
14.Secondary Outcome
Title Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months
Hide Description Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24 or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 24 (end of combination phase) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms.
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only subjects in the ITT Population with data available at the week 24 time point were analysed. Only subjects with data available for analysis are presented.
Arm/Group Title Combination Phase
Hide Arm/Group Description:

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6.

Overall Number of Participants Analyzed 34
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Endocrine symptoms Number Analyzed 34 participants
-1.0  (13.5)
Gastrointestinal (G.I.) symptoms Number Analyzed 34 participants
5.7  (14.0)
Treatment related symptoms Number Analyzed 14 participants
3.6  (30.1)
Social function Number Analyzed 34 participants
2.3  (25.3)
Disease related worries Number Analyzed 34 participants
1.6  (27.1)
Muscle/bone pain symptoms Number Analyzed 34 participants
1.0  (37.1)
Body image Number Analyzed 34 participants
0.0  (23.2)
Weight gain Number Analyzed 31 participants
-11.8  (30.5)
Information/communication function Number Analyzed 32 participants
-9.4  (22.8)
Sexual function Number Analyzed 14 participants
-4.8  (17.8)
15.Secondary Outcome
Title QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months
Hide Description Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Answers were converted into grading scale, with values between 0 and 100. Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 48 (end of study) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms.
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
Only subjects in the ITT Population with data available at the week 48 time point were analysed. Only subjects with data available for analysis are presented.
Arm/Group Title Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Hide Arm/Group Description:
In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24.
After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24.
Overall Number of Participants Analyzed 5 8 7
Mean (Standard Deviation)
Unit of Measure: units on a scale
Endocrine symptoms Number Analyzed 5 participants 8 participants 7 participants
-13.3  (21.4) -5.6  (19.7) 1.6  (4.2)
G.I. symptoms Number Analyzed 5 participants 8 participants 7 participants
-4.0  (21.9) 0.0  (19.2) 6.7  (7.7)
Treatment related symptoms Number Analyzed 2 participants 3 participants 0 participants
0.0  (0.0) -11.1  (34.7)
Social function Number Analyzed 5 participants 8 participants 7 participants
-6.7  (23.0) 9.7  (20.9) -6.3  (16.8)
Disease related worries Number Analyzed 5 participants 8 participants 7 participants
-6.7  (36.5) 1.4  (15.1) -3.2  (30.6)
Muscle/bone pain symptoms Number Analyzed 5 participants 8 participants 7 participants
-6.7  (14.9) 4.2  (33.0) 4.8  (30.0)
Body image Number Analyzed 5 participants 8 participants 7 participants
0.0  (23.6) 4.2  (27.8) 4.8  (12.6)
Weight gain Number Analyzed 5 participants 7 participants 7 participants
-20.0  (29.8) 9.5  (25.2) -9.5  (56.8)
Information/communication function Number Analyzed 5 participants 8 participants 7 participants
0.0  (70.7) 0.0  (17.8) -4.8  (12.6)
Sexual function Number Analyzed 2 participants 4 participants 3 participants
0.0  (0.0) 0.0  (0.0) 0.0  (0.0)
16.Secondary Outcome
Title DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months
Hide Description

In all subjects whose tumour tissue was available, MGMT expression/methylation and SSTR expression was analysed. After 6 months, the DCR (SD+PR+CR) by MGMT methylation and expression and by SSTR 2a and SSTR 5 expression was evaluated.

DCR in response to MGMT methylation and expression results are presented. SSTR 2a and SSTR 5 expression is categorised as: No Receptors, Cytoplasmatic Expression (CE), Focal Expression (FE), Complete Circumferent Membrane Expression (CCME).

The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment within each methylation/expression category. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test.

Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Percentages are based on the number of subjects in the ITT population and with data available for analysis.
Arm/Group Title Combination Phase
Hide Arm/Group Description:

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6

Overall Number of Participants Analyzed 49
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
MGMT Methylation Number Analyzed 9 participants
100.0
(66.4 to 100.0)
MGMT No methylation Number Analyzed 13 participants
84.6
(54.6 to 98.1)
MGMT Expression Number Analyzed 11 participants
90.9
(58.7 to 99.8)
MGMT No expression Number Analyzed 20 participants
70.0
(45.7 to 88.1)
SSTR 2a No Receptors Number Analyzed 0 participants
SSTR 2a CE Number Analyzed 0 participants
SSTR 2a FE Number Analyzed 15 participants
86.7
(59.5 to 98.3)
SSTR 2a CCME Number Analyzed 22 participants
72.7
(49.8 to 89.3)
SSTR 5 - No Receptors Number Analyzed 24 participants
75.0
(53.3 to 90.2)
SSTR 5 CE Number Analyzed 2 participants
100.0
(15.8 to 100.0)
SSTR 5 FE Number Analyzed 11 participants
81.8
(48.2 to 97.7)
SSTR 5 CCME Number Analyzed 0 participants
17.Secondary Outcome
Title Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months
Hide Description

Lanreotide ATG levels were measured in a subset of subjects to evaluate if temozolomide co-treatment had an impact on lanreotide serum concentration over a 12 month period.

Blood samples were collected for the determination of lanreotide ATG in serum at baseline, weeks 4, 12, 24 and 48 (end of study).

The concentrations of lanreotide ATG in serum were determined by a validated radioimmunoassay analysis method with a lower limit of quantitation of 0.08 nanograms [ng]/mL).

Serum concentrations of lanreotide ATG at each of the time points in the combination and maintenance phase are presented. Only subjects with data available for analysis are presented.

Time Frame Baseline (week 1) and weeks 4, 12, 24 and 48
Hide Outcome Measure Data
Hide Analysis Population Description
PK analysis was performed using the valid PK population.
Arm/Group Title PK Subset
Hide Arm/Group Description:
All subjects for whom PK assessments were performed and with evaluable PK data.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: ng/mL
Baseline Number Analyzed 16 participants
0.44  (1.22)
Week 4 Number Analyzed 14 participants
2.45  (1.16)
Week 12 Number Analyzed 11 participants
5.06  (3.01)
Week 24 Number Analyzed 9 participants
5.83  (1.93)
Week 48 Number Analyzed 7 participants
3.68  (3.36)
Time Frame 13 months (12 month study treatment plus 28 days)
Adverse Event Reporting Description Treatment Emergent Adverse Events (TEAEs) are reported for both the combination and maintenance phases and include events with an onset after the start of study drug treatment to the last intake of study drug plus 28 days.
 
Arm/Group Title Combination Phase Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Hide Arm/Group Description

All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.

Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6.

In case of clinical benefit, defined as either CR, PR or SD, after the first 6 months combination phase all subjects with functioning NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24.
All-Cause Mortality
Combination Phase Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/57 (1.75%)      1/11 (9.09%)      1/14 (7.14%)      1/12 (8.33%)    
Show Serious Adverse Events Hide Serious Adverse Events
Combination Phase Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/57 (29.82%)      3/11 (27.27%)      4/14 (28.57%)      4/12 (33.33%)    
Blood and lymphatic system disorders         
Thrombocytopenia  1  3/57 (5.26%)  3 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Leukocytosis  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cardiac disorders         
Cardiac failure  1  2/57 (3.51%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Congestive cardiomyopathy  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Tricuspid valve incompetence  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Eye disorders         
Ocular vascular disorder  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorders         
Diarrhoea  1  2/57 (3.51%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Ileus  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Intestinal perforation  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Nausea  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Vomiting  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Abdominal pain  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Ascites  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
General disorders         
Asthenia  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
General physical health deterioration  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Oedema  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Peripheral swelling  1  1/57 (1.75%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Multi-organ failure  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Pyrexia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Hepatobiliary disorders         
Cholangitis  1  2/57 (3.51%)  2 0/11 (0.00%)  0 1/14 (7.14%)  2 1/12 (8.33%)  1
Bile duct stenosis  1  1/57 (1.75%)  3 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Hyperbilirubinaemia  1  1/57 (1.75%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Jaundice  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations         
Pneumonia  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Injury, poisoning and procedural complications         
Ankle fracture  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Investigations         
Blood creatinine increased  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
C-reactive protein increased  1  1/57 (1.75%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Metabolism and nutrition disorders         
Diabetes mellitus  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Hypercalcaemia  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Cachexia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Hyperglycaemia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Musculoskeletal and connective tissue disorders         
Arthralgia  1  1/57 (1.75%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Myalgia  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Seronegative arthritis  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Back pain  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Metastases to gastrointestinal tract  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Metastases to peritoneum  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Penile squamous cell carcinoma  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Psychiatric disorders         
Depression  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Pulmonary embolism  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders         
Petechiae  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA18.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Combination Phase Maintenance Phase - Functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, Lanreotide Maintenance Phase - Non-functioning NET, No Treatment
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   52/57 (91.23%)      9/11 (81.82%)      13/14 (92.86%)      11/12 (91.67%)    
Blood and lymphatic system disorders         
Anaemia  1  7/57 (12.28%)  9 0/11 (0.00%)  0 0/14 (0.00%)  0 3/12 (25.00%)  3
Coagulopathy  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  2 0/12 (0.00%)  0
Leukocytosis  1  1/57 (1.75%)  2 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Leukopenia  1  6/57 (10.53%)  8 0/11 (0.00%)  0 0/14 (0.00%)  0 3/12 (25.00%)  3
Lymphadenopathy  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Lymphopenia  1  8/57 (14.04%)  10 0/11 (0.00%)  0 2/14 (14.29%)  2 4/12 (33.33%)  8
Neutropenia  1  6/57 (10.53%)  7 1/11 (9.09%)  1 0/14 (0.00%)  0 1/12 (8.33%)  1
Thrombocytopenia  1  16/57 (28.07%)  28 1/11 (9.09%)  1 3/14 (21.43%)  3 0/12 (0.00%)  0
Cardiac disorders         
Arrhythmia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Atrial thrombosis  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Atrioventricular block  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Bradycardia  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Cardiac failure  1  2/57 (3.51%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Diastolic dysfunction  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Mitral valve incompetence  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Palpitations  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Tricuspid valve incompetence  1  2/57 (3.51%)  2 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Ventricular extrasystoles  1  1/57 (1.75%)  1 0/11 (0.00%)  0 2/14 (14.29%)  2 1/12 (8.33%)  1
Ear and labyrinth disorders         
Tinnitus  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Vertigo  1  3/57 (5.26%)  6 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Endocrine disorders         
Hypothyroidism  1  1/57 (1.75%)  1 1/11 (9.09%)  1 1/14 (7.14%)  1 0/12 (0.00%)  0
Eye disorders         
Ocular vascular disorder  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Photopsia  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Gastrointestinal disorders         
Abdominal pain upper  1  3/57 (5.26%)  3 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Abdominal discomfort  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Abdominal distension  1  4/57 (7.02%)  7 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Abdominal pain  1  12/57 (21.05%)  22 2/11 (18.18%)  3 4/14 (28.57%)  6 2/12 (16.67%)  2
Anal inflammation  1  1/57 (1.75%)  2 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Ascites  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Constipation  1  11/57 (19.30%)  16 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Diarrhoea  1  21/57 (36.84%)  35 0/11 (0.00%)  0 3/14 (21.43%)  4 2/12 (16.67%)  2
Dyspepsia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Eructation  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Faecal incontinence  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Flatulence  1  10/57 (17.54%)  16 1/11 (9.09%)  1 2/14 (14.29%)  3 1/12 (8.33%)  1
Frequent bowel movements  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Intestinal ischaemia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Lip dry  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Melaena  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Nausea  1  24/57 (42.11%)  55 1/11 (9.09%)  1 4/14 (28.57%)  5 1/12 (8.33%)  1
Pancreatic insufficiency  1  1/57 (1.75%)  1 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Steatorrhoea  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Vomiting  1  19/57 (33.33%)  40 1/11 (9.09%)  1 2/14 (14.29%)  3 1/12 (8.33%)  1
General disorders         
Administration site extravasation  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Asthenia  1  3/57 (5.26%)  3 1/11 (9.09%)  1 2/14 (14.29%)  2 1/12 (8.33%)  1
Chest discomfort  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  2 0/12 (0.00%)  0
Fatigue  1  19/57 (33.33%)  32 2/11 (18.18%)  2 4/14 (28.57%)  4 5/12 (41.67%)  7
Feeling cold  1  2/57 (3.51%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
General physical health deterioration  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Injection site pain  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Oedema peripheral  1  4/57 (7.02%)  4 0/11 (0.00%)  0 1/14 (7.14%)  1 2/12 (16.67%)  2
Pain  1  2/57 (3.51%)  2 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Pyrexia  1  4/57 (7.02%)  5 1/11 (9.09%)  1 3/14 (21.43%)  4 3/12 (25.00%)  8
Thirst  1  1/57 (1.75%)  1 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Hepatobiliary disorders         
Cholangitis  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  2 0/12 (0.00%)  0
Hepatic pain  1  3/57 (5.26%)  3 2/11 (18.18%)  2 0/14 (0.00%)  0 1/12 (8.33%)  1
Infections and infestations         
Bronchitis  1  1/57 (1.75%)  1 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Nasopharyngitis  1  7/57 (12.28%)  8 3/11 (27.27%)  4 2/14 (14.29%)  3 3/12 (25.00%)  3
Otitis media  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Respiratory tract infection  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 1/12 (8.33%)  1
Sinusitis  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Injury, poisoning and procedural complications         
Fall  1  2/57 (3.51%)  2 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Investigations         
Blood bilirubin increased  1  3/57 (5.26%)  4 0/11 (0.00%)  0 0/14 (0.00%)  0 0/12 (0.00%)  0
Blood alkaline phosphatase increased  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 2/12 (16.67%)  2
Blood creatinine increased  1  3/57 (5.26%)  3 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Blood uric acid increased  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
C-reactive protein increased  1  2/57 (3.51%)  4 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Gamma-glutamyltransferase increased  1  6/57 (10.53%)  6 1/11 (9.09%)  2 1/14 (7.14%)  1 1/12 (8.33%)  1
Liver function test abnormal  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Platelet count decreased  1  2/57 (3.51%)  2 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Red blood cell count decreased  1  1/57 (1.75%)  1 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Weight decreased  1  8/57 (14.04%)  8 0/11 (0.00%)  0 2/14 (14.29%)  2 3/12 (25.00%)  3
Metabolism and nutrition disorders         
Cachexia  1  1/57 (1.75%)  1 1/11 (9.09%)  1 1/14 (7.14%)  1 1/12 (8.33%)  1
Decreased appetite  1  3/57 (5.26%)  3 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Dehydration  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Diabetes mellitus  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Electrolyte imbalance  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Glucose tolerance impaired  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Hypercalcaemia  1  2/57 (3.51%)  2 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Hypercholesterolaemia  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 2/12 (16.67%)  2
Hyperkalaemia  1  2/57 (3.51%)  2 0/11 (0.00%)  0 2/14 (14.29%)  2 2/12 (16.67%)  2
Hypertriglyceridaemia  1  2/57 (3.51%)  2 0/11 (0.00%)  0 0/14 (0.00%)  0 2/12 (16.67%)  4
Hypocalcaemia  1  2/57 (3.51%)  2 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Hypokalaemia  1  3/57 (5.26%)  3 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Vitamin D deficiency  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Arthralgia  1  5/57 (8.77%)  9 1/11 (9.09%)  1 2/14 (14.29%)  2 1/12 (8.33%)  1
Back pain  1  2/57 (3.51%)  2 0/11 (0.00%)  0 1/14 (7.14%)  1 2/12 (16.67%)  2
Joint swelling  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Muscle tightness  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Musculoskeletal chest pain  1  0/57 (0.00%)  0 1/11 (9.09%)  4 0/14 (0.00%)  0 0/12 (0.00%)  0
Pain in extremity  1  3/57 (5.26%)  3 1/11 (9.09%)  1 0/14 (0.00%)  0 1/12 (8.33%)  1
Synovial cyst  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Lipoma  1  2/57 (3.51%)  3 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Neoplasm progression  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Tumour pain  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Nervous system disorders         
Carotid arteriosclerosis  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Disturbance in attention  1  1/57 (1.75%)  2 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Dizziness  1  3/57 (5.26%)  6 0/11 (0.00%)  0 0/14 (0.00%)  0 2/12 (16.67%)  2
Dysgeusia  1  1/57 (1.75%)  1 0/11 (0.00%)  0 3/14 (21.43%)  3 0/12 (0.00%)  0
Headache  1  7/57 (12.28%)  9 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Hypoaesthesia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Polyneuropathy  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Presyncope  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Syncope  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  2
Tremor  1  1/57 (1.75%)  2 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Psychiatric disorders         
Depression  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Disorientation  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Insomnia  1  3/57 (5.26%)  3 0/11 (0.00%)  0 2/14 (14.29%)  2 0/12 (0.00%)  0
Renal and urinary disorders         
Urinary incontinence  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Respiratory, thoracic and mediastinal disorders         
Cough  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Dysphonia  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Dyspnoea  1  3/57 (5.26%)  6 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Dyspnoea exertional  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Pleural effusion  1  0/57 (0.00%)  0 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Sleep apnoea syndrome  1  1/57 (1.75%)  1 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Skin and subcutaneous tissue disorders         
Dry skin  1  0/57 (0.00%)  0 1/11 (9.09%)  1 0/14 (0.00%)  0 0/12 (0.00%)  0
Erythema  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 0/12 (0.00%)  0
Night sweats  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  1 1/12 (8.33%)  1
Pruritus  1  2/57 (3.51%)  2 1/11 (9.09%)  1 2/14 (14.29%)  2 0/12 (0.00%)  0
Rash  1  5/57 (8.77%)  6 2/11 (18.18%)  2 2/14 (14.29%)  2 1/12 (8.33%)  1
Vascular disorders         
Flushing  1  1/57 (1.75%)  1 0/11 (0.00%)  0 0/14 (0.00%)  0 1/12 (8.33%)  1
Haematoma  1  3/57 (5.26%)  5 1/11 (9.09%)  3 0/14 (0.00%)  0 0/12 (0.00%)  0
Hypertension  1  5/57 (8.77%)  5 1/11 (9.09%)  1 2/14 (14.29%)  2 2/12 (16.67%)  2
Lymphoedema  1  0/57 (0.00%)  0 0/11 (0.00%)  0 1/14 (7.14%)  2 0/12 (0.00%)  0
1
Term from vocabulary, MedDRA18.0
Indicates events were collected by systematic assessment
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.
No publication of the Study Results shall be made without the Sponsor's prior written approval which shall not be unreasonably withheld. Sponsor must be provided with the final version of any abstract, presentation or paper before submission, and the Sponsor shall provide scientific comments within 2 weeks for an abstract or presentation or 6 weeks for an article. If no comments are received within these periods, this silence of Sponsor can be considered as approval to proceed to publication.
Results Point of Contact
Name/Title: Medical Director
Organization: Ipsen
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02231762     History of Changes
Other Study ID Numbers: A-94-52030-268
2013‐001697‐17 ( EudraCT Number )
First Submitted: September 2, 2014
First Posted: September 4, 2014
Results First Submitted: July 18, 2018
Results First Posted: May 6, 2019
Last Update Posted: May 6, 2019