Trial Outcomes & Findings for Circulating Tumour Cells in Somatuline Autogel Treated NeuroEndocrine Tumours Patients (NCT NCT02075606)
NCT ID: NCT02075606
Last Updated: 2019-06-07
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
50 participants
Primary outcome timeframe
From baseline up to Week 53.
Results posted on
2019-06-07
Participant Flow
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.
Overall, 54 subjects were screened, 50 of whom were enrolled and treated in the study.
Participant milestones
| Measure |
Lanreotide Autogel
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.
|
|---|---|
|
Overall Study
STARTED
|
50
|
|
Overall Study
COMPLETED
|
40
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
Lanreotide Autogel
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.
|
|---|---|
|
Overall Study
Adverse Event
|
5
|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
Death
|
1
|
|
Overall Study
Investigator's decision
|
1
|
|
Overall Study
Symptom management
|
1
|
|
Overall Study
Increasing Symptoms
|
1
|
Baseline Characteristics
Circulating Tumour Cells in Somatuline Autogel Treated NeuroEndocrine Tumours Patients
Baseline characteristics by cohort
| Measure |
Lanreotide Autogel
n=50 Participants
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.
|
|---|---|
|
Age, Continuous
years
|
63.4 years
STANDARD_DEVIATION 8.6 • n=5 Participants
|
|
Sex: Female, Male
Female
|
23 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
27 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
45 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From baseline up to Week 53.Population: 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.
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.
Outcome measures
| Measure |
CTC Presence at Baseline
n=22 Participants
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.
|
No CTC Presence at Baseline
n=26 Participants
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.
|
Lanreotide Autogel
n=50 Participants
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.
|
Lanreotide Autogel
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.
|
|---|---|---|---|---|
|
Assessment of Clinical Symptomatic Response
Clinical Symptomatic Response = Yes(2)
|
77.8 Percentage of Subjects
Interval 54.8 to 91.0
|
95.5 Percentage of Subjects
Interval 78.2 to 99.2
|
87.5 Percentage of Subjects
Interval 73.9 to 94.5
|
—
|
|
Assessment of Clinical Symptomatic Response
Clinical Symptomatic Response = No(3)
|
22.2 Percentage of Subjects
Interval 9.0 to 45.2
|
4.5 Percentage of Subjects
Interval 0.8 to 21.8
|
12.5 Percentage of Subjects
Interval 5.5 to 26.1
|
—
|
PRIMARY outcome
Timeframe: Week 25 and Week 53.Population: 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.
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.
Outcome measures
| Measure |
CTC Presence at Baseline
n=22 Participants
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.
|
No CTC Presence at Baseline
n=26 Participants
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.
|
Lanreotide Autogel
n=50 Participants
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.
|
Lanreotide Autogel
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.
|
|---|---|---|---|---|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 53: Progressive Disease
|
26.7 percentage of subjects
Interval 10.9 to 52.0
|
31.8 percentage of subjects
Interval 16.4 to 52.7
|
29.7 percentage of subjects
Interval 17.5 to 45.8
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 25: Complete Response
|
0.0 percentage of subjects
Interval 0.0 to 25.9
|
0.0 percentage of subjects
Interval 0.0 to 24.2
|
0.0 percentage of subjects
Interval 0.0 to 14.3
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 25: Partial Response
|
18.2 percentage of subjects
Interval 5.1 to 47.7
|
8.3 percentage of subjects
Interval 1.5 to 35.4
|
13.0 percentage of subjects
Interval 4.5 to 32.1
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 25: Stable Disease
|
72.7 percentage of subjects
Interval 43.4 to 90.3
|
75.0 percentage of subjects
Interval 46.8 to 91.1
|
73.9 percentage of subjects
Interval 53.5 to 87.5
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 25: Progressive Disease
|
9.1 percentage of subjects
Interval 1.6 to 37.7
|
16.7 percentage of subjects
Interval 4.7 to 44.8
|
13.0 percentage of subjects
Interval 4.5 to 32.1
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 25: Non evaluable
|
0.0 percentage of subjects
Interval 0.0 to 25.9
|
0.0 percentage of subjects
Interval 0.0 to 24.2
|
0.0 percentage of subjects
Interval 0.0 to 14.3
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 53: Complete Response
|
0.0 percentage of subjects
Interval 0.0 to 20.4
|
0.0 percentage of subjects
Interval 0.0 to 14.9
|
0.0 percentage of subjects
Interval 0.0 to 9.4
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 53: Partial Response
|
6.7 percentage of subjects
Interval 1.2 to 29.8
|
4.5 percentage of subjects
Interval 0.8 to 21.8
|
5.4 percentage of subjects
Interval 1.5 to 17.7
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 53: Stable Disease
|
66.7 percentage of subjects
Interval 41.7 to 84.8
|
63.6 percentage of subjects
Interval 43.0 to 80.3
|
64.9 percentage of subjects
Interval 48.8 to 78.2
|
—
|
|
Percentage of Subjects With Time Point Responses According to Response Evaluation Criteria in Solid Tumours (RECIST) Assessments at Weeks 25 and 53
Week 53: Non evaluable
|
0.0 percentage of subjects
Interval 0.0 to 20.4
|
0.0 percentage of subjects
Interval 0.0 to 14.9
|
0.0 percentage of subjects
Interval 0.0 to 9.4
|
—
|
SECONDARY outcome
Timeframe: From baseline up to Week 53.Population: 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.
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.
Outcome measures
| Measure |
CTC Presence at Baseline
n=22 Participants
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.
|
No CTC Presence at Baseline
n=26 Participants
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.
|
Lanreotide Autogel
n=2 Participants
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.
|
Lanreotide Autogel
n=50 Participants
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.
|
|---|---|---|---|---|
|
Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing
Diarrhoea: Visit 2 (daily)
|
-0.66 number of episodes
Interval -1.68 to 0.36
|
-0.27 number of episodes
Interval -0.73 to 0.2
|
0.38 number of episodes
Interval -11.18 to 11.93
|
-0.42 number of episodes
Interval -0.92 to 0.08
|
|
Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing
Diarrhoea: Visit 14 (days 11-17)
|
-1.91 number of episodes
Interval -3.24 to 0.57
|
-0.64 number of episodes
Interval -1.16 to -0.11
|
—
|
-1.18 number of episodes
Interval -1.83 to -0.54
|
|
Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing
Diarrhoea: Visit 14 (days 11-28)
|
-2.15 number of episodes
Interval -3.49 to -0.82
|
-0.63 number of episodes
Interval -1.19 to -0.08
|
—
|
-1.30 number of episodes
Interval -1.98 to -0.63
|
|
Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing
Flushing: Visit 2 (daily)
|
-1.76 number of episodes
Interval -3.41 to -0.11
|
-1.25 number of episodes
Interval -2.02 to -0.48
|
0.00 number of episodes
Interval 0.0 to 0.0
|
-1.43 number of episodes
Interval -2.24 to -0.62
|
|
Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing
Flushing: Visit 14 (days 11-17)
|
-3.37 number of episodes
Interval -5.76 to -0.98
|
-2.51 number of episodes
Interval -3.68 to -1.33
|
—
|
-2.88 number of episodes
Interval -4.05 to -1.71
|
|
Mean Change From Baseline in Number of Episodes of Diarrhoea and Flushing
Flushing: Visit 14 (days 11-28)
|
-3.49 number of episodes
Interval -6.0 to -0.99
|
-2.23 number of episodes
Interval -3.34 to -1.13
|
—
|
-2.79 number of episodes
Interval -3.99 to -1.58
|
SECONDARY outcome
Timeframe: From baseline up to Week 53.Population: 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.
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.
Outcome measures
| Measure |
CTC Presence at Baseline
n=22 Participants
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.
|
No CTC Presence at Baseline
n=26 Participants
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.
|
Lanreotide Autogel
n=2 Participants
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.
|
Lanreotide Autogel
n=50 Participants
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.
|
|---|---|---|---|---|
|
Mode Symptom Severity of Episodes of Flushing
No flushing: Baseline
|
22.7 percentage of subjects
Interval 10.1 to 43.4
|
0.0 percentage of subjects
Interval 0.0 to 12.9
|
100 percentage of subjects
Interval 34.2 to 100.0
|
14.0 percentage of subjects
Interval 7.0 to 26.2
|
|
Mode Symptom Severity of Episodes of Flushing
Mild: Baseline
|
27.3 percentage of subjects
Interval 13.2 to 48.2
|
50.0 percentage of subjects
Interval 32.1 to 67.9
|
0.0 percentage of subjects
Interval 0.0 to 65.8
|
38.0 percentage of subjects
Interval 25.9 to 51.8
|
|
Mode Symptom Severity of Episodes of Flushing
Moderate: Baseline
|
45.5 percentage of subjects
Interval 26.9 to 65.3
|
50.0 percentage of subjects
Interval 32.1 to 67.9
|
0.0 percentage of subjects
Interval 0.0 to 65.8
|
46.0 percentage of subjects
Interval 33.0 to 59.6
|
|
Mode Symptom Severity of Episodes of Flushing
Severe: Baseline
|
4.5 percentage of subjects
Interval 0.8 to 21.8
|
0.0 percentage of subjects
Interval 0.0 to 12.9
|
0.0 percentage of subjects
Interval 0.0 to 65.8
|
2.0 percentage of subjects
Interval 0.4 to 10.5
|
|
Mode Symptom Severity of Episodes of Flushing
No flushing: Visit 14 (days 11-17)
|
37.5 percentage of subjects
Interval 18.5 to 61.4
|
28.6 percentage of subjects
Interval 13.8 to 50.0
|
—
|
32.4 percentage of subjects
Interval 19.6 to 48.5
|
|
Mode Symptom Severity of Episodes of Flushing
Mild: Visit 14 (days 11-17)
|
43.8 percentage of subjects
Interval 23.1 to 66.8
|
47.6 percentage of subjects
Interval 28.3 to 67.6
|
—
|
45.9 percentage of subjects
Interval 31.0 to 61.6
|
|
Mode Symptom Severity of Episodes of Flushing
Moderate: Visit 14 (days 11-17)
|
18.8 percentage of subjects
Interval 6.6 to 43.0
|
23.8 percentage of subjects
Interval 10.6 to 45.1
|
—
|
21.6 percentage of subjects
Interval 11.4 to 37.2
|
|
Mode Symptom Severity of Episodes of Flushing
Severe: Visit 14 (days 11-17)
|
0.0 percentage of subjects
Interval 0.0 to 19.4
|
0.0 percentage of subjects
Interval 0.0 to 15.5
|
—
|
0.0 percentage of subjects
Interval 0.0 to 9.4
|
|
Mode Symptom Severity of Episodes of Flushing
No flushing: Visit 14 (days 11-28)
|
13.3 percentage of subjects
Interval 3.7 to 37.9
|
31.6 percentage of subjects
Interval 15.4 to 54.0
|
—
|
23.5 percentage of subjects
Interval 12.4 to 40.0
|
|
Mode Symptom Severity of Episodes of Flushing
Mild: Visit 14 (days 11-28)
|
60.0 percentage of subjects
Interval 35.7 to 80.2
|
52.6 percentage of subjects
Interval 31.7 to 72.7
|
—
|
55.9 percentage of subjects
Interval 39.5 to 71.1
|
|
Mode Symptom Severity of Episodes of Flushing
Moderate: Visit 14 (days 11-28)
|
26.7 percentage of subjects
Interval 10.9 to 52.0
|
10.5 percentage of subjects
Interval 2.9 to 31.4
|
—
|
17.6 percentage of subjects
Interval 8.3 to 33.5
|
|
Mode Symptom Severity of Episodes of Flushing
Severe: Visit 14 (days 11-28)
|
0.0 percentage of subjects
Interval 0.0 to 20.4
|
5.3 percentage of subjects
Interval 0.9 to 24.6
|
—
|
2.9 percentage of subjects
Interval 0.5 to 14.9
|
SECONDARY outcome
Timeframe: From baseline up to Week 53.Population: 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.
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.
Outcome measures
| Measure |
CTC Presence at Baseline
n=50 Participants
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.
|
No CTC Presence at Baseline
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.
|
Lanreotide Autogel
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.
|
Lanreotide Autogel
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.
|
|---|---|---|---|---|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Fatigue: Visit 8
|
-6.3 Units on a scale
Standard Deviation 21.2
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Physical functioning: Visit 5
|
1.2 Units on a scale
Standard Deviation 17.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Physical functioning: Visit 8
|
2.0 Units on a scale
Standard Deviation 17.6
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Physical functioning: End of study
|
1.9 Units on a scale
Standard Deviation 21.7
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Role functioning: Visit 5
|
1.3 Units on a scale
Standard Deviation 30.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Role functioning: Visit 8
|
3.2 Units on a scale
Standard Deviation 32.1
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Role functioning: End of study
|
-1.4 Units on a scale
Standard Deviation 33.7
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Emotional functioning: Visit 5
|
6.1 Units on a scale
Standard Deviation 24.8
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Emotional functioning: Visit 8
|
4.3 Units on a scale
Standard Deviation 18.3
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Emotional functioning: End of study
|
1.1 Units on a scale
Standard Deviation 23.0
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Cognitive functioning: Visit 5
|
-0.9 Units on a scale
Standard Deviation 19.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Cognitive functioning: Visit 8
|
1.5 Units on a scale
Standard Deviation 15.6
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Cognitive functioning: End of study
|
-2.4 Units on a scale
Standard Deviation 19.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Social functioning: Visit 5
|
10.0 Units on a scale
Standard Deviation 26.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Social functioning: Visit 8
|
4.5 Units on a scale
Standard Deviation 30.1
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Social functioning: End of study
|
3.9 Units on a scale
Standard Deviation 27.8
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Global QoL: Visit 5
|
12.5 Units on a scale
Standard Deviation 26.4
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Global QoL: Visit 8
|
7.4 Units on a scale
Standard Deviation 24.3
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Global QoL: End of study
|
4.3 Units on a scale
Standard Deviation 22.8
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Fatigue: Visit 5
|
-4.4 Units on a scale
Standard Deviation 26.7
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Fatigue: End of study
|
-4.2 Units on a scale
Standard Deviation 25.6
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Nausea and vomiting: Visit 5
|
-4.2 Units on a scale
Standard Deviation 20.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Nausea and vomiting: Visit 8
|
-1.4 Units on a scale
Standard Deviation 20.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Nausea and vomiting: End of study
|
-0.9 Units on a scale
Standard Deviation 29.1
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Pain: Visit 5
|
-7.9 Units on a scale
Standard Deviation 32.5
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Pain: Visit 8
|
-2.3 Units on a scale
Standard Deviation 30.2
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Pain: End of study
|
1.8 Units on a scale
Standard Deviation 30.6
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Dyspnoea: Visit 5
|
-3.5 Units on a scale
Standard Deviation 25.5
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Dyspnoea: Visit 8
|
1.0 Units on a scale
Standard Deviation 20.6
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Dyspnoea: End of study
|
-4.8 Units on a scale
Standard Deviation 30.4
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Insomnia: Visit 5
|
-6.3 Units on a scale
Standard Deviation 27.0
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Insomnia: Visit 8
|
-5.7 Units on a scale
Standard Deviation 22.1
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Insomnia: End of study
|
-2.9 Units on a scale
Standard Deviation 37.0
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Appetite loss: Visit 5
|
-0.9 Units on a scale
Standard Deviation 37.1
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Appetite loss: Visit 8
|
-6.5 Units on a scale
Standard Deviation 36.4
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Appetite loss: End of study
|
-0.0 Units on a scale
Standard Deviation 34.7
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Constipation: Visit 5
|
1.9 Units on a scale
Standard Deviation 19.4
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Constipation: Visit 8
|
-1.0 Units on a scale
Standard Deviation 13.1
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Constipation: End of study
|
1.9 Units on a scale
Standard Deviation 13.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Diarrhoea: Visit 5
|
-18.5 Units on a scale
Standard Deviation 33.3
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Diarrhoea: Visit 8
|
-12.7 Units on a scale
Standard Deviation 30.7
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Diarrhoea: End of study
|
-10.8 Units on a scale
Standard Deviation 32.5
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Financial difficulties: Visit 5
|
-6.7 Units on a scale
Standard Deviation 25.3
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Financial difficulties: Visit 8
|
-4.0 Units on a scale
Standard Deviation 30.9
|
—
|
—
|
—
|
|
Quality of Life (QoL) Questionnaire: European Organisation for Research and Treatment of Cancer (EORTC) QoL Questionnaire (QLQ)-C30
Financial difficulties: End of study
|
-1.0 Units on a scale
Standard Deviation 38.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline up to Week 53.Population: 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.
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.
Outcome measures
| Measure |
CTC Presence at Baseline
n=50 Participants
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.
|
No CTC Presence at Baseline
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.
|
Lanreotide Autogel
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.
|
Lanreotide Autogel
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.
|
|---|---|---|---|---|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Treatment symptoms: End of study
|
12.0 Units on a scale
Standard Deviation 12.4
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Information/communication function: Visit 8
|
-3.7 Units on a scale
Standard Deviation 31.7
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Body image: End of study
|
-1.0 Units on a scale
Standard Deviation 35.8
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Social function: End of study
|
-4.5 Units on a scale
Standard Deviation 24.1
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Disease related worries: Visit 5
|
-14.1 Units on a scale
Standard Deviation 25.2
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Disease related worries: Visit 8
|
-15.9 Units on a scale
Standard Deviation 33.8
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Disease related worries: End of study
|
-12.2 Units on a scale
Standard Deviation 36.3
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Muscle/Bone pain: Visit 5
|
-7.9 Units on a scale
Standard Deviation 36.7
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Muscle/Bone pain: Visit 8
|
-6.5 Units on a scale
Standard Deviation 31.7
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Muscle/Bone pain: End of study
|
-11.8 Units on a scale
Standard Deviation 39.3
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Sexual function: Visit 5
|
-5.6 Units on a scale
Standard Deviation 34.8
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Sexual function: Visit 8
|
-8.9 Units on a scale
Standard Deviation 34.4
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Sexual function: End of study
|
-13.3 Units on a scale
Standard Deviation 27.6
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Information/communication function: Visit 5
|
-8.5 Units on a scale
Standard Deviation 26.2
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Information/communication function: End of study
|
-5.6 Units on a scale
Standard Deviation 25.8
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Body image: Visit 5
|
0.9 Units on a scale
Standard Deviation 41.0
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Body image: Visit 8
|
1.9 Units on a scale
Standard Deviation 41.2
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Endocrine symptoms: Visit 5
|
-15.4 Units on a scale
Standard Deviation 21.6
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Endocrine symptoms: Visit 8
|
-17.0 Units on a scale
Standard Deviation 22.9
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Endocrine symptoms: End of study
|
-16.0 Units on a scale
Standard Deviation 22.8
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Gastrointestinal symptoms: Visit 5
|
2.1 Units on a scale
Standard Deviation 16.9
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Gastrointestinal symptoms: Visit 8
|
1.2 Units on a scale
Standard Deviation 15.6
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Gastrointestinal symptoms: End of study
|
1.0 Units on a scale
Standard Deviation 16.7
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Treatment symptoms: Visit 5
|
1.2 Units on a scale
Standard Deviation 15.2
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Treatment symptoms: Visit 8
|
7.6 Units on a scale
Standard Deviation 8.9
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Social function: Visit 5
|
-11.3 Units on a scale
Standard Deviation 26.6
|
—
|
—
|
—
|
|
QoL Questionnaire: EORTC QLQ-G.I.NET21
Social function: Visit 8
|
-6.5 Units on a scale
Standard Deviation 29.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: From baseline up to Week 53.Population: 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.
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.
Outcome measures
| Measure |
CTC Presence at Baseline
n=22 Participants
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.
|
No CTC Presence at Baseline
n=26 Participants
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.
|
Lanreotide Autogel
n=50 Participants
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.
|
Lanreotide Autogel
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.
|
|---|---|---|---|---|
|
Percentage of Subjects Alive and Progression Free at One Year
|
69.00 percentage of subjects
Interval 40.3 to 85.94
|
67.75 percentage of subjects
Interval 43.42 to 83.39
|
66.43 percentage of subjects
Interval 48.77 to 79.22
|
—
|
Adverse Events
Lanreotide Autogel
Serious events: 12 serious events
Other events: 47 other events
Deaths: 3 deaths
Serious adverse events
| Measure |
Lanreotide Autogel
n=50 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Cardiac failure
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Cardiac disorders
Myocardial infarction
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Abdominal pain
|
4.0%
2/50 • Number of events 2 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Intestinal obstruction
|
4.0%
2/50 • Number of events 2 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Nausea
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Vomiting
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
General physical health deterioration
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
General disorders
Multi-organ failure
|
4.0%
2/50 • Number of events 2 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Hepatobiliary disorders
Hepatic failure
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Infections and infestations
Pneumonia
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Injury, poisoning and procedural complications
Hip fracture
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Investigations
Biopsy lymph gland
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Investigations
C-reactive protein increased
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Investigations
Campylobacter test positive
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.0%
1/50 • Number of events 2 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
2.0%
1/50 • Number of events 2 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
2.0%
1/50 • Number of events 2 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Malnutrition
|
2.0%
1/50 • Number of events 2 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Renal and urinary disorders
Acute kidney injury
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Surgical and medical procedures
Cardiac pacemaker insertion
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Surgical and medical procedures
Small intestinal resection
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Vascular disorders
Orthostatic hypotension
|
2.0%
1/50 • Number of events 1 • From baseline to Week 53 (approximately 1 year).
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.
|
Other adverse events
| Measure |
Lanreotide Autogel
n=50 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Palpitations
|
10.0%
5/50 • Number of events 6 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Abdominal discomfort
|
10.0%
5/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Abdominal pain
|
32.0%
16/50 • Number of events 20 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
22.0%
11/50 • Number of events 14 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Constipation
|
18.0%
9/50 • Number of events 9 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Diarrhoea
|
48.0%
24/50 • Number of events 29 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Flatulence
|
10.0%
5/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Gastrointestinal pain
|
6.0%
3/50 • Number of events 3 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Nausea
|
26.0%
13/50 • Number of events 16 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Gastrointestinal disorders
Vomiting
|
14.0%
7/50 • Number of events 13 • From baseline to Week 53 (approximately 1 year).
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.
|
|
General disorders
Chest pain
|
6.0%
3/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
General disorders
Fatigue
|
32.0%
16/50 • Number of events 19 • From baseline to Week 53 (approximately 1 year).
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.
|
|
General disorders
Injection site mass
|
10.0%
5/50 • Number of events 6 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Hepatobiliary disorders
Hepatic pain
|
6.0%
3/50 • Number of events 3 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Infections and infestations
Ear infection
|
10.0%
5/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Infections and infestations
Lower respiratory tract infection
|
14.0%
7/50 • Number of events 8 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Infections and infestations
Nasopharyngitis
|
12.0%
6/50 • Number of events 7 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Investigations
Weight decreased
|
14.0%
7/50 • Number of events 7 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
14.0%
7/50 • Number of events 9 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.0%
4/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
12.0%
6/50 • Number of events 7 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
12.0%
6/50 • Number of events 8 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
10.0%
5/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
14.0%
7/50 • Number of events 12 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
10.0%
5/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
14.0%
7/50 • Number of events 8 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Nervous system disorders
Dizziness
|
24.0%
12/50 • Number of events 16 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Nervous system disorders
Headache
|
22.0%
11/50 • Number of events 25 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Nervous system disorders
Sciatica
|
6.0%
3/50 • Number of events 4 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Nervous system disorders
Tremor
|
6.0%
3/50 • Number of events 5 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Psychiatric disorders
Insomnia
|
6.0%
3/50 • Number of events 3 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
8.0%
4/50 • Number of events 4 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Vascular disorders
Flushing
|
14.0%
7/50 • Number of events 9 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Vascular disorders
Hypertension
|
8.0%
4/50 • Number of events 4 • From baseline to Week 53 (approximately 1 year).
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.
|
|
Vascular disorders
Hypotension
|
6.0%
3/50 • Number of events 3 • From baseline to Week 53 (approximately 1 year).
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place