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Trial record 4 of 34 for:    Lanreotide | Neuroendocrine Tumors

Circulating Tumour Cells in Somatuline Autogel Treated NeuroEndocrine Tumours Patients (CALM-NET)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02075606
Recruitment Status : Completed
First Posted : March 3, 2014
Results First Posted : June 7, 2019
Last Update Posted : June 7, 2019
Sponsor:
Information provided by (Responsible Party):
Ipsen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Diagnostic
Condition NeuroEndocrine Tumours
Intervention Drug: lanreotide acetate
Enrollment 50
Recruitment Details Recruitment to this prospective, pilot, phase IV, multicentre, open-label, single-group study began on 16 May 2014. Subjects with a documented diagnosis of functioning midgut NET and who suffered from symptoms of diarrhoea and/or flushing at the time of enrolment were recruited to 11 study centres in the United Kingdom.
Pre-assignment Details Overall, 54 subjects were screened, 50 of whom were enrolled and treated in the study.
Arm/Group Title Lanreotide Autogel
Hide Arm/Group Description

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 milligrams (mg) every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Period Title: Overall Study
Started 50
Completed 40
Not Completed 10
Reason Not Completed
Adverse Event             5
Withdrawal by Subject             1
Death             1
Investigator's decision             1
Symptom management             1
Increasing Symptoms             1
Arm/Group Title Lanreotide Autogel
Hide Arm/Group Description

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Baseline Participants 50
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
years Number Analyzed 50 participants
63.4  (8.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
Female
23
  46.0%
Male
27
  54.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 50 participants
American Indian or Alaska Native
0
   0.0%
Asian
2
   4.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
3
   6.0%
White
45
  90.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
1.Primary Outcome
Title Assessment of Clinical Symptomatic Response
Hide Description

This endpoint was assessed using 2 efficacy variables:

  • CTCs, enumerated at baseline and Weeks 5, 17, 25, 53
  • Clinical symptomatic response, assessed by the use of symptom reporting

Subjects recorded 24-hour symptom frequency and severity for 7 days prior to first treatment (baseline), throughout the study, and up to 28 days following final drug administration. Symptoms were recorded by answering predetermined questions on the interactive voice response system (IVRS).

Subjects were considered to have a clinical symptomatic response between baseline and last study visit if any 1 of the following criteria were fulfilled: the average number of episodes of diarrhoea decreased by at least 50%, the average number of episodes of flushing decreased by at least 50%, the mode severity of flushing decreased by at least 1 level. Clinical symptomatic response was assessed as a qualitative variable (Yes/No) and reported according to CTC presence at baseline and overall.

Time Frame From baseline up to Week 53.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the Intention-to-treat (ITT) population, defined as all enrolled subjects who received at least one injection of study medication. Only subjects with data available for analysis are presented.
Arm/Group Title CTC Presence at Baseline No CTC Presence at Baseline Lanreotide Autogel
Hide Arm/Group Description:

Subjects with a baseline presence of CTCs, determined by either or both baseline CTC blood samples having a CTC enumeration >0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects with no baseline presence of CTCs, determined by both baseline CTC blood samples having a CTC enumeration = 0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Participants Analyzed 22 26 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Subjects
Clinical Symptomatic Response = Yes(2)
77.8
(54.8 to 91.0)
95.5
(78.2 to 99.2)
87.5
(73.9 to 94.5)
Clinical Symptomatic Response = No(3)
22.2
(9.0 to 45.2)
4.5
(0.8 to 21.8)
12.5
(5.5 to 26.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CTC Presence at Baseline, No CTC Presence at Baseline
Comments Clinical symptomatic response as dependent variable and CTC presence at baseline as explanatory variable was used to perform the logistic regression analysis.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.126
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.02 to 1.65
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Hide Description

Subjects underwent Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) scans at baseline, Visit 8 (Week 25) and Visit 15 (Week 53). Progression was assessed by investigators using RECIST v1.1, and classified as a complete response, partial response, stable disease, progressive disease or non evaluable.

The time point responses at Week 25 and Week 53 were analysed by CTC presence at baseline and overall. The percentage of subjects within each response category are presented. Percentages are based on the number of subjects in the concerned population with available responses.

Time Frame Week 25 and Week 53.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on subjects from the ITT population, defined as all enrolled subjects who received at least one injection of study medication. Only subjects with data available for analysis are presented.
Arm/Group Title CTC Presence at Baseline No CTC Presence at Baseline Lanreotide Autogel
Hide Arm/Group Description:

Subjects with a baseline presence of CTCs, determined by either or both baseline CTC blood samples having a CTC enumeration >0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects with no baseline presence of CTCs, determined by both baseline CTC blood samples having a CTC enumeration = 0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Participants Analyzed 22 26 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
Week 25: Complete Response Number Analyzed 11 participants 12 participants 23 participants
0.0
(0.0 to 25.9)
0.0
(0.0 to 24.2)
0.0
(0.0 to 14.3)
Week 25: Partial Response Number Analyzed 11 participants 12 participants 23 participants
18.2
(5.1 to 47.7)
8.3
(1.5 to 35.4)
13.0
(4.5 to 32.1)
Week 25: Stable Disease Number Analyzed 11 participants 12 participants 23 participants
72.7
(43.4 to 90.3)
75.0
(46.8 to 91.1)
73.9
(53.5 to 87.5)
Week 25: Progressive Disease Number Analyzed 11 participants 12 participants 23 participants
9.1
(1.6 to 37.7)
16.7
(4.7 to 44.8)
13.0
(4.5 to 32.1)
Week 25: Non evaluable Number Analyzed 11 participants 12 participants 23 participants
0.0
(0.0 to 25.9)
0.0
(0.0 to 24.2)
0.0
(0.0 to 14.3)
Week 53: Complete Response Number Analyzed 15 participants 22 participants 37 participants
0.0
(0.0 to 20.4)
0.0
(0.0 to 14.9)
0.0
(0.0 to 9.4)
Week 53: Partial Response Number Analyzed 15 participants 22 participants 37 participants
6.7
(1.2 to 29.8)
4.5
(0.8 to 21.8)
5.4
(1.5 to 17.7)
Week 53: Stable Disease Number Analyzed 15 participants 22 participants 37 participants
66.7
(41.7 to 84.8)
63.6
(43.0 to 80.3)
64.9
(48.8 to 78.2)
Week 53: Progressive Disease Number Analyzed 15 participants 22 participants 37 participants
26.7
(10.9 to 52.0)
31.8
(16.4 to 52.7)
29.7
(17.5 to 45.8)
Week 53: Non evaluable Number Analyzed 15 participants 22 participants 37 participants
0.0
(0.0 to 20.4)
0.0
(0.0 to 14.9)
0.0
(0.0 to 9.4)
3.Secondary Outcome
Title Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing
Hide Description

The effect of lanreotide Autogel on the symptoms of diarrhoea and flushing in subjects was assessed through subject reporting of symptoms every 24-hours for the 7 days prior to treatment (baseline), for the first 16 weeks and on days 11 to 17 after each subsequent injection interval. After the final study drug injection at Week 49, subjects provided 24-hour symptom frequency on days 11 to 28 (up to Week 53). Symptom frequency was recorded by answering predetermined questions on the IVRS.

Mean change from baseline in frequency (number of episodes) of diarrhoea and flushing are described at Visit 2 (average number of episodes in Week 1) and at Visit 14 (average number of episodes over days 11 to 17 after Week 49 injection and over days 11 to 28 after Week 49 injection) by CTC presence at baseline and overall. A negative change indicates an improvement in symptoms from baseline.

Time Frame From baseline up to Week 53.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT population, defined as all enrolled subjects who received at least one injection of study medication. Only subjects with data available for analysis at each time point are reported.
Arm/Group Title CTC Presence at Baseline No CTC Presence at Baseline Missing CTC Status at Baseline Lanreotide Autogel
Hide Arm/Group Description:

Subjects with a baseline presence of CTCs, determined by either or both baseline CTC blood samples having a CTC enumeration >0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects with no baseline presence of CTCs, determined by both baseline CTC blood samples having a CTC enumeration = 0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects whose CTC status at baseline could not be evaluated as both CTC blood samples were missing. Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Participants Analyzed 22 26 2 50
Mean (95% Confidence Interval)
Unit of Measure: number of episodes
Diarrhoea: Visit 2 (daily) Number Analyzed 22 participants 25 participants 2 participants 49 participants
-0.66
(-1.68 to 0.36)
-0.27
(-0.73 to 0.20)
0.38
(-11.18 to 11.93)
-0.42
(-0.92 to 0.08)
Diarrhoea: Visit 14 (days 11-17) Number Analyzed 16 participants 21 participants 0 participants 37 participants
-1.91
(-3.24 to 0.57)
-0.64
(-1.16 to -0.11)
-1.18
(-1.83 to -0.54)
Diarrhoea: Visit 14 (days 11-28) Number Analyzed 15 participants 19 participants 0 participants 34 participants
-2.15
(-3.49 to -0.82)
-0.63
(-1.19 to -0.08)
-1.30
(-1.98 to -0.63)
Flushing: Visit 2 (daily) Number Analyzed 22 participants 25 participants 2 participants 49 participants
-1.76
(-3.41 to -0.11)
-1.25
(-2.02 to -0.48)
0.00
(0.00 to 0.00)
-1.43
(-2.24 to -0.62)
Flushing: Visit 14 (days 11-17) Number Analyzed 16 participants 21 participants 0 participants 37 participants
-3.37
(-5.76 to -0.98)
-2.51
(-3.68 to -1.33)
-2.88
(-4.05 to -1.71)
Flushing: Visit 14 (days 11-28) Number Analyzed 15 participants 19 participants 0 participants 34 participants
-3.49
(-6.00 to -0.99)
-2.23
(-3.34 to -1.13)
-2.79
(-3.99 to -1.58)
4.Secondary Outcome
Title Mode Symptom Severity of Episodes of Flushing
Hide Description The effect of lanreotide Autogel on the mode severity of flushing was assessed through subject reporting of symptoms every 24-hours for the 7 days prior to treatment (baseline), for the first 16 weeks and on days 11 to 17 after each subsequent injection interval until Week 49. After the final study drug injection at Week 49, subjects provided 24-hour symptom severity on days 11 to 28 (up to Week 53). Symptom severity was recorded by answering predetermined questions on the IVRS using a three-point system (mild, moderate or severe). The mode (most frequent) intensity of flushing are reported at baseline and at Visit 14 (average number of episodes over days 11 to 17 after Week 49 injection and over days 11 to 28 after Week 49 injection). Percentages of subjects in each severity category are based on the number of subjects in the analysis set with available responses. Data is presented according to CTC presence at baseline and overall.
Time Frame From baseline up to Week 53.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT population, defined as all enrolled subjects who received at least one injection of study medication. Only subjects with data available for analysis are presented.
Arm/Group Title CTC Presence at Baseline No CTC Presence at Baseline Missing CTC Status at Baseline Lanreotide Autogel
Hide Arm/Group Description:

Subjects with a baseline presence of CTCs, determined by either or both baseline CTC blood samples having a CTC enumeration >0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects with no baseline presence of CTCs, determined by both baseline CTC blood samples having a CTC enumeration = 0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects whose CTC status at baseline could not be evaluated as both CTC blood samples were missing. Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Participants Analyzed 22 26 2 50
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
No flushing: Baseline Number Analyzed 22 participants 26 participants 2 participants 50 participants
22.7
(10.1 to 43.4)
0.0
(0.0 to 12.9)
100
(34.2 to 100)
14.0
(7.0 to 26.2)
Mild: Baseline Number Analyzed 22 participants 26 participants 2 participants 50 participants
27.3
(13.2 to 48.2)
50.0
(32.1 to 67.9)
0.0
(0.0 to 65.8)
38.0
(25.9 to 51.8)
Moderate: Baseline Number Analyzed 22 participants 26 participants 2 participants 50 participants
45.5
(26.9 to 65.3)
50.0
(32.1 to 67.9)
0.0
(0.0 to 65.8)
46.0
(33.0 to 59.6)
Severe: Baseline Number Analyzed 22 participants 26 participants 2 participants 50 participants
4.5
(0.8 to 21.8)
0.0
(0.0 to 12.9)
0.0
(0.0 to 65.8)
2.0
(0.4 to 10.5)
No flushing: Visit 14 (days 11-17) Number Analyzed 16 participants 21 participants 0 participants 37 participants
37.5
(18.5 to 61.4)
28.6
(13.8 to 50.0)
32.4
(19.6 to 48.5)
Mild: Visit 14 (days 11-17) Number Analyzed 16 participants 21 participants 0 participants 37 participants
43.8
(23.1 to 66.8)
47.6
(28.3 to 67.6)
45.9
(31.0 to 61.6)
Moderate: Visit 14 (days 11-17) Number Analyzed 16 participants 21 participants 0 participants 37 participants
18.8
(6.6 to 43.0)
23.8
(10.6 to 45.1)
21.6
(11.4 to 37.2)
Severe: Visit 14 (days 11-17) Number Analyzed 16 participants 21 participants 0 participants 37 participants
0.0
(0.0 to 19.4)
0.0
(0.0 to 15.5)
0.0
(0.0 to 9.4)
No flushing: Visit 14 (days 11-28) Number Analyzed 15 participants 19 participants 0 participants 34 participants
13.3
(3.7 to 37.9)
31.6
(15.4 to 54.0)
23.5
(12.4 to 40.0)
Mild: Visit 14 (days 11-28) Number Analyzed 15 participants 19 participants 0 participants 34 participants
60.0
(35.7 to 80.2)
52.6
(31.7 to 72.7)
55.9
(39.5 to 71.1)
Moderate: Visit 14 (days 11-28) Number Analyzed 15 participants 19 participants 0 participants 34 participants
26.7
(10.9 to 52.0)
10.5
(2.9 to 31.4)
17.6
(8.3 to 33.5)
Severe: Visit 14 (days 11-28) Number Analyzed 15 participants 19 participants 0 participants 34 participants
0.0
(0.0 to 20.4)
5.3
(0.9 to 24.6)
2.9
(0.5 to 14.9)
5.Secondary Outcome
Title Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Hide Description

The effect of lanreotide Autogel treatment on QoL was assessed using the EORTC QLQ-C30 at baseline, Weeks 13 (Visit 5), 25 (Visit 8) and 53 (Visit 15/end of study). The 30 item scale is divided into 9 multi item scales (including 5 functional scales, 1 global health status/QoL scale and 3 general symptom scales) and 6 single items. Possible answers to the first 28 items (all items except the 2 concerning global quality of life) go from 1 (Not at all) to 4 (Very much). The answers for the 2 last questions (Q29- 30) go from 1 (Very poor) to 7 (Excellent). All of the scales and single-item measures range in score from 0 to 100. For multi-item scales, the raw score will be calculated by the addition of item responses divided by the number of items. Higher scores for global health and functional domains indicate a better QoL, while higher symptom scores indicate worse symptoms.

The mean change from baseline at each time point is reported for each of the category subscores.

Time Frame From baseline up to Week 53.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT population, defined as all enrolled subjects who received at least one injection of study medication. Only subjects with data available for analysis are presented.
Arm/Group Title Lanreotide Autogel
Hide Arm/Group Description:

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Physical functioning: Visit 5 Number Analyzed 39 participants
1.2  (17.9)
Physical functioning: Visit 8 Number Analyzed 36 participants
2.0  (17.6)
Physical functioning: End of study Number Analyzed 36 participants
1.9  (21.7)
Role functioning: Visit 5 Number Analyzed 39 participants
1.3  (30.9)
Role functioning: Visit 8 Number Analyzed 36 participants
3.2  (32.1)
Role functioning: End of study Number Analyzed 36 participants
-1.4  (33.7)
Emotional functioning: Visit 5 Number Analyzed 36 participants
6.1  (24.8)
Emotional functioning: Visit 8 Number Analyzed 34 participants
4.3  (18.3)
Emotional functioning: End of study Number Analyzed 35 participants
1.1  (23.0)
Cognitive functioning: Visit 5 Number Analyzed 36 participants
-0.9  (19.9)
Cognitive functioning: Visit 8 Number Analyzed 34 participants
1.5  (15.6)
Cognitive functioning: End of study Number Analyzed 35 participants
-2.4  (19.9)
Social functioning: Visit 5 Number Analyzed 35 participants
10.0  (26.9)
Social functioning: Visit 8 Number Analyzed 33 participants
4.5  (30.1)
Social functioning: End of study Number Analyzed 34 participants
3.9  (27.8)
Global QoL: Visit 5 Number Analyzed 36 participants
12.5  (26.4)
Global QoL: Visit 8 Number Analyzed 34 participants
7.4  (24.3)
Global QoL: End of study Number Analyzed 35 participants
4.3  (22.8)
Fatigue: Visit 5 Number Analyzed 39 participants
-4.4  (26.7)
Fatigue: Visit 8 Number Analyzed 36 participants
-6.3  (21.2)
Fatigue: End of study Number Analyzed 36 participants
-4.2  (25.6)
Nausea and vomiting: Visit 5 Number Analyzed 40 participants
-4.2  (20.9)
Nausea and vomiting: Visit 8 Number Analyzed 37 participants
-1.4  (20.9)
Nausea and vomiting: End of study Number Analyzed 37 participants
-0.9  (29.1)
Pain: Visit 5 Number Analyzed 40 participants
-7.9  (32.5)
Pain: Visit 8 Number Analyzed 37 participants
-2.3  (30.2)
Pain: End of study Number Analyzed 37 participants
1.8  (30.6)
Dyspnoea: Visit 5 Number Analyzed 38 participants
-3.5  (25.5)
Dyspnoea: Visit 8 Number Analyzed 35 participants
1.0  (20.6)
Dyspnoea: End of study Number Analyzed 35 participants
-4.8  (30.4)
Insomnia: Visit 5 Number Analyzed 37 participants
-6.3  (27.0)
Insomnia: Visit 8 Number Analyzed 35 participants
-5.7  (22.1)
Insomnia: End of study Number Analyzed 34 participants
-2.9  (37.0)
Appetite loss: Visit 5 Number Analyzed 34 participants
-0.9  (37.1)
Appetite loss: Visit 8 Number Analyzed 36 participants
-6.5  (36.4)
Appetite loss: End of study Number Analyzed 36 participants
-0.0  (34.7)
Constipation: Visit 5 Number Analyzed 36 participants
1.9  (19.4)
Constipation: Visit 8 Number Analyzed 33 participants
-1.0  (13.1)
Constipation: End of study Number Analyzed 35 participants
1.9  (13.9)
Diarrhoea: Visit 5 Number Analyzed 36 participants
-18.5  (33.3)
Diarrhoea: Visit 8 Number Analyzed 34 participants
-12.7  (30.7)
Diarrhoea: End of study Number Analyzed 34 participants
-10.8  (32.5)
Financial difficulties: Visit 5 Number Analyzed 35 participants
-6.7  (25.3)
Financial difficulties: Visit 8 Number Analyzed 33 participants
-4.0  (30.9)
Financial difficulties: End of study Number Analyzed 34 participants
-1.0  (38.0)
6.Secondary Outcome
Title QoL Questionnaire: EORTC QLQ-G.I.NET21
Hide Description The effect of lanreotide Autogel treatment on QoL was assessed using the EORTC QLQ-G.I.NET21 at baseline, Weeks 13 (Visit 5), 25 (Visit 8) and 53 (Visit 15/end of study). The QLQ-G.I.NET21 questionnaire 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. Higher scores indicate worse symptoms or more problems. The mean change from baseline at each time point is reported for each of the category subscores.
Time Frame From baseline up to Week 53.
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on the ITT population, defined as all enrolled subjects who received at least one injection of study medication. Only subjects with data available for analysis are presented.
Arm/Group Title Lanreotide Autogel
Hide Arm/Group Description:

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Participants Analyzed 50
Mean (Standard Deviation)
Unit of Measure: Units on a scale
Endocrine symptoms: Visit 5 Number Analyzed 39 participants
-15.4  (21.6)
Endocrine symptoms: Visit 8 Number Analyzed 37 participants
-17.0  (22.9)
Endocrine symptoms: End of study Number Analyzed 36 participants
-16.0  (22.8)
Gastrointestinal symptoms: Visit 5 Number Analyzed 39 participants
2.1  (16.9)
Gastrointestinal symptoms: Visit 8 Number Analyzed 37 participants
1.2  (15.6)
Gastrointestinal symptoms: End of study Number Analyzed 36 participants
1.0  (16.7)
Treatment symptoms: Visit 5 Number Analyzed 9 participants
1.2  (15.2)
Treatment symptoms: Visit 8 Number Analyzed 8 participants
7.6  (8.9)
Treatment symptoms: End of study Number Analyzed 6 participants
12.0  (12.4)
Social function: Visit 5 Number Analyzed 39 participants
-11.3  (26.6)
Social function: Visit 8 Number Analyzed 37 participants
-6.5  (29.3)
Social function: End of study Number Analyzed 36 participants
-4.5  (24.1)
Disease related worries: Visit 5 Number Analyzed 39 participants
-14.1  (25.2)
Disease related worries: Visit 8 Number Analyzed 37 participants
-15.9  (33.8)
Disease related worries: End of study Number Analyzed 36 participants
-12.2  (36.3)
Muscle/Bone pain: Visit 5 Number Analyzed 38 participants
-7.9  (36.7)
Muscle/Bone pain: Visit 8 Number Analyzed 36 participants
-6.5  (31.7)
Muscle/Bone pain: End of study Number Analyzed 34 participants
-11.8  (39.3)
Sexual function: Visit 5 Number Analyzed 18 participants
-5.6  (34.8)
Sexual function: Visit 8 Number Analyzed 15 participants
-8.9  (34.4)
Sexual function: End of study Number Analyzed 15 participants
-13.3  (27.6)
Information/communication function: Visit 5 Number Analyzed 39 participants
-8.5  (26.2)
Information/communication function: Visit 8 Number Analyzed 36 participants
-3.7  (31.7)
Information/communication function: End of study Number Analyzed 36 participants
-5.6  (25.8)
Body image: Visit 5 Number Analyzed 36 participants
0.9  (41.0)
Body image: Visit 8 Number Analyzed 35 participants
1.9  (41.2)
Body image: End of study Number Analyzed 35 participants
-1.0  (35.8)
7.Secondary Outcome
Title Percentage of Subjects Alive and Progression Free at One Year
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Subjects underwent CT or MRI scans at baseline and Week 53. Progression was assessed by investigators using RECIST v1.1. The best overall response to study treatment is the highest time point response achieved by the subject and was assessed as a complete response, partial response, stable disease, progressive disease or non evaluable. For analysis of PFS, event dates were assigned to the first time that progressive disease was noted or the date of death. In case of progressive disease followed by death, the first event was considered in the analysis. Censoring dates were defined in subjects with no progressive disease or death before end of study.

At one year (end of study), the mean percentage of subjects who were alive and progression free, as calculated using the Kaplan-Meier method, is reported by CTC presence and overall.

Time Frame From baseline up to Week 53.
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Hide Analysis Population Description
Analysis was performed on the ITT population, defined as all enrolled subjects who received at least one injection of study medication. Only subjects with data available for analysis are presented.
Arm/Group Title CTC Presence at Baseline No CTC Presence at Baseline Lanreotide Autogel
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Subjects with a baseline presence of CTCs, determined by either or both baseline CTC blood samples having a CTC enumeration >0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects with no baseline presence of CTCs, determined by both baseline CTC blood samples having a CTC enumeration = 0.

Baseline is defined as the 7 days preceding the first study treatment injection, or for subjects who required a washout period, these 7 days were during the washout period.

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

Overall Number of Participants Analyzed 22 26 50
Mean (95% Confidence Interval)
Unit of Measure: percentage of subjects
69.00
(40.3 to 85.94)
67.75
(43.42 to 83.39)
66.43
(48.77 to 79.22)
Time Frame From baseline to Week 53 (approximately 1 year).
Adverse Event Reporting Description Treatment emergent adverse events are reported and defined as any adverse event that occurred from the first study drug injection until 28 days after the last study drug injection.
 
Arm/Group Title Lanreotide Autogel
Hide Arm/Group Description

Subjects received deep subcutaneous injections of lanreotide Autogel for 1 year to treat the symptoms of functioning midgut NETs.

A washout period was required for subjects receiving either subcutaneous octreotide (at least 2 weeks) or 1 injection of long-acting somatostatin analogue (at least 6 weeks) prior to treatment in the study.

Initially subjects began treatment with a dose of lanreotide Autogel 120 mg every 28 days for 3 months. Thereafter, the dose administered was determined on an individual subject basis by the treating clinician. Subjects could remain on the 120 mg dose, or be titrated to either 60 mg or 90 mg lanreotide Autogel, administered every 28 days according to their symptomatic response.

All-Cause Mortality
Lanreotide Autogel
Affected / at Risk (%)
Total   3/50 (6.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Lanreotide Autogel
Affected / at Risk (%) # Events
Total   12/50 (24.00%)    
Cardiac disorders   
Cardiac failure  1  1/50 (2.00%)  1
Myocardial infarction  1  1/50 (2.00%)  1
Gastrointestinal disorders   
Abdominal pain upper  1  1/50 (2.00%)  1
Abdominal pain  1  2/50 (4.00%)  2
Diarrhoea  1  1/50 (2.00%)  1
Intestinal obstruction  1  2/50 (4.00%)  2
Nausea  1  1/50 (2.00%)  1
Vomiting  1  1/50 (2.00%)  1
General physical health deterioration  1  1/50 (2.00%)  1
General disorders   
Multi-organ failure  1  2/50 (4.00%)  2
Hepatobiliary disorders   
Hepatic failure  1  1/50 (2.00%)  1
Infections and infestations   
Pneumonia  1  1/50 (2.00%)  1
Injury, poisoning and procedural complications   
Hip fracture  1  1/50 (2.00%)  1
Investigations   
Biopsy lymph gland  1  1/50 (2.00%)  1
C-reactive protein increased  1  1/50 (2.00%)  1
Campylobacter test positive  1  1/50 (2.00%)  1
Metabolism and nutrition disorders   
Dehydration  1  1/50 (2.00%)  2
Hyperkalaemia  1  1/50 (2.00%)  1
Hypoglycaemia  1  1/50 (2.00%)  2
Hypokalaemia  1  1/50 (2.00%)  2
Hypomagnesaemia  1  1/50 (2.00%)  1
Hyponatraemia  1  1/50 (2.00%)  1
Malnutrition  1  1/50 (2.00%)  2
Renal and urinary disorders   
Acute kidney injury  1  1/50 (2.00%)  1
Surgical and medical procedures   
Cardiac pacemaker insertion  1  1/50 (2.00%)  1
Small intestinal resection  1  1/50 (2.00%)  1
Vascular disorders   
Orthostatic hypotension  1  1/50 (2.00%)  1
1
Term from vocabulary, MedDRA
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%
Lanreotide Autogel
Affected / at Risk (%) # Events
Total   47/50 (94.00%)    
Cardiac disorders   
Palpitations  1  5/50 (10.00%)  6
Gastrointestinal disorders   
Abdominal discomfort  1  5/50 (10.00%)  5
Abdominal pain  1  16/50 (32.00%)  20
Abdominal pain upper  1  11/50 (22.00%)  14
Constipation  1  9/50 (18.00%)  9
Diarrhoea  1  24/50 (48.00%)  29
Flatulence  1  5/50 (10.00%)  5
Gastrointestinal pain  1  3/50 (6.00%)  3
Nausea  1  13/50 (26.00%)  16
Vomiting  1  7/50 (14.00%)  13
General disorders   
Chest pain  1  3/50 (6.00%)  5
Fatigue  1  16/50 (32.00%)  19
Injection site mass  1  5/50 (10.00%)  6
Hepatobiliary disorders   
Hepatic pain  1  3/50 (6.00%)  3
Infections and infestations   
Ear infection  1  5/50 (10.00%)  5
Lower respiratory tract infection  1  7/50 (14.00%)  8
Nasopharyngitis  1  6/50 (12.00%)  7
Investigations   
Weight decreased  1  7/50 (14.00%)  7
Metabolism and nutrition disorders   
Decreased appetite  1  7/50 (14.00%)  9
Musculoskeletal and connective tissue disorders   
Arthralgia  1  4/50 (8.00%)  5
Back pain  1  6/50 (12.00%)  7
Muscle spasms  1  6/50 (12.00%)  8
Musculoskeletal chest pain  1  5/50 (10.00%)  5
Musculoskeletal pain  1  7/50 (14.00%)  12
Myalgia  1  5/50 (10.00%)  5
Pain in extremity  1  7/50 (14.00%)  8
Nervous system disorders   
Dizziness  1  12/50 (24.00%)  16
Headache  1  11/50 (22.00%)  25
Sciatica  1  3/50 (6.00%)  4
Tremor  1  3/50 (6.00%)  5
Psychiatric disorders   
Insomnia  1  3/50 (6.00%)  3
Respiratory, thoracic and mediastinal disorders   
Dyspnoea  1  4/50 (8.00%)  4
Vascular disorders   
Flushing  1  7/50 (14.00%)  9
Hypertension  1  4/50 (8.00%)  4
Hypotension  1  3/50 (6.00%)  3
1
Term from vocabulary, MedDRA (18.0)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Medical Director
Organization: Ipsen
Phone: 00441753627777
Responsible Party: Ipsen
ClinicalTrials.gov Identifier: NCT02075606     History of Changes
Other Study ID Numbers: A-97-52030-270
2013-002194-22 ( EudraCT Number )
First Submitted: February 26, 2014
First Posted: March 3, 2014
Results First Submitted: September 6, 2018
Results First Posted: June 7, 2019
Last Update Posted: June 7, 2019