Gastroenteropancreatic Neuroendocrine Tumors
Conditions
Brief summary
The purpose of the study is to evaluate the efficacy and tolerability of the combination of Lanreotide Autogel 120 mg and Temozolomide in patients with progressive gastro-entero-pancreatic neuroendocrine tumours (GEP-NET) graded as G1 or G2 (G1/G2). All progressive tumours classified according to Response Evaluation Criteria In Solid Tumours (RECIST, 1.1).
Interventions
Lanreotide Autogel 120 mg subcutaneous (s.c) - injection, every 28 days (+/-2 days).
DRUGTemozolomide (TMZ)
Temozolomide capsule (variable dose). 150 mg/m2 per day for 5 days in the first month. 200 mg/m2 per day for 5 days in months 2, 3, 4, 5 and 6.
Sponsors
Ipsen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of written informed consent prior to any study related procedures * Inoperable, Gastro-Entero-Pancreatic-Neuroendocrine Tumour G1 or G2 (Proliferation Index, Ki67-Index: 0 to ≤20%) confirmed by pathological/histological assessment * Progressive disease within 12 months before inclusion (RECIST 1.1: increase of \>20% tumour load; by Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) * Measurable disease according to RECIST 1.1. * Metastatic disease confirmed by CT/MRI. * Functioning or non-functioning NET (G1, G2). * Positive Octreo-Scan (≥ Grade 2 Krenning scale) or positive DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid)-TATE (Tyr3-Thre8-Octreotide or DOTA-Tyr3-octreotate)/TOC (Tyr3-octreotide) -PET (Positron-Emission-Tomography) -CT within 12 months prior to screening
Exclusion criteria
* Has the diagnosis of Insulinoma * Has a diagnosis of a multiple endocrine neoplasia (MEN)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) After 6 Months | 6 months | All tumour assessments were performed using the Response Evaluation Criteria In Solid Tumours (RECIST) criteria (1.1). Computer Tomography (CT-scan) or Magnetic Resonance Imaging (MRI) could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at weeks 12, 24 and at early withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression. The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment and was described in the ITT population along with its 95% Confidence Interval (CI) and was compared to 45% with an exact binomial proportion test. The Last Observation Carried Forward (LOCF) method was used to replace missing assessments at the end of the combination phase. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) Within 12 Months | 12 months | PFS was defined as the time from the date of treatment start to the date of the first documented disease progression or death due to any cause within the first 12 months of treatment. If a subject had not progressed or died after 12 months of treatment or when any further anti-neoplastic therapy was received, PFS was censored at the time of the last tumour assessment before the analysis cut-off date or the anti-neoplastic therapy date. A Kaplan-Meier estimate of the PFS was calculated to determine the number of subjects at risk. Median PFS time (50% of subjects who would not progress or die) of the ITT population is presented along with 95 % CI. |
| Time To Response (TtR) Within 12 Months | 12 months | TtR was defined as the time from the date of treatment start to the date of the first documented objective response (CR or PR) within the first 12 months of treatment (combination and maintenance phases). A Kaplan Meier estimate of the TtR survival function was constructed. The Kaplan-Meier method was used to estimate the median TtR and its 95% CI for subjects in the ITT population (50% of subjects were expected to have a CR or PR at this time). |
| Duration of Response (DoR) Within 12 Months | 12 months | The DoR is an estimation of the time from first documented objective response (CR or PR) to the first date of progressive disease (PD) or death due to disease progression for subjects who experienced an objective response within the first 12 months of treatment (combination and maintenance phases). The Kaplan-Meier method was used to estimate the median DoR and its 95% CI for subjects in the ITT population who had an objective response. |
| The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | 6 months | Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24 and at early withdrawal. The biochemical response after 6 months combination treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 micrograms/litre \[mcg/L\]). Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥ 50%, compared to the baseline CgA), SD (decrease \< 50 % or an increase ≤25%, compared to the baseline CgA) or PD (defined as an increase ≥25 %, compared to the baseline CgA). The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline. |
| The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | 12 months | Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and at early withdrawal. The biochemical response after 12 months combination and maintenance treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 mcg/L). Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥50 % compared to the baseline CgA), SD (decrease \< 50% or an increase ≤ 25% compared to the baseline CgA) or PD (defined as an increase ≥ 25%, compared to the baseline CgA). The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline. |
| The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | 6 months | Urine samples for 5-HIAA urinary tumour marker analysis were taken at at baseline, weeks 12, 24and early withdrawal. Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline). The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
| The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | 12 months | Urine samples for 5-HIAA urinary tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and early withdrawal. Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline). The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
| DCR After 12 Months | 12 months | All tumour assessments were performed using the RECIST criteria (1.1). CT-scan or MRI could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at baseline, weeks 12, 24, 36, 48 (end of study) and at study withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression. The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months combination treatment followed by either 6 months of lanreotide ATG 120 mg maintenance treatment or no treatment. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test. The LOCF method was used to replace missing assessments at the end of the maintenance phase. |
| The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | 12 months | Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline. Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing. The number of subjects in each response category at week 48 (end of study) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
| European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | 6 months | Subjects were instructed to complete the QLQ-C30 questionnaire at baseline, weeks 12, 24 or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 24 (end of the combination phase) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms. |
| EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | 12 months | Subjects were instructed to complete QLQ-C30 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 48 (end of study) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms. |
| Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | 6 months | Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24 or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 24 (end of combination phase) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms. |
| QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | 12 months | Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Answers were converted into grading scale, with values between 0 and 100. Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 48 (end of study) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms. |
| DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | 6 months | In all subjects whose tumour tissue was available, MGMT expression/methylation and SSTR expression was analysed. After 6 months, the DCR (SD+PR+CR) by MGMT methylation and expression and by SSTR 2a and SSTR 5 expression was evaluated. DCR in response to MGMT methylation and expression results are presented. SSTR 2a and SSTR 5 expression is categorised as: No Receptors, Cytoplasmatic Expression (CE), Focal Expression (FE), Complete Circumferent Membrane Expression (CCME). The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment within each methylation/expression category. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test. |
| Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months | Baseline (week 1) and weeks 4, 12, 24 and 48 | Lanreotide ATG levels were measured in a subset of subjects to evaluate if temozolomide co-treatment had an impact on lanreotide serum concentration over a 12 month period. Blood samples were collected for the determination of lanreotide ATG in serum at baseline, weeks 4, 12, 24 and 48 (end of study). The concentrations of lanreotide ATG in serum were determined by a validated radioimmunoassay analysis method with a lower limit of quantitation of 0.08 nanograms \[ng\]/mL). Serum concentrations of lanreotide ATG at each of the time points in the combination and maintenance phase are presented. Only subjects with data available for analysis are presented. |
| The Number of Subjects With a Symptomatic Response After 6 Months | 6 months | Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline. Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing. The number of subjects in each response category at week 24 (end of the combination phase) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
Countries
Austria, Germany
Participant flow
Recruitment details
57 subjects entered a combination phase and received lanreotide ATG 120 mg plus temozolomide for 6 months. A 6 month maintenance phase then followed where subjects received either lanreotide ATG 120 mg or no treatment, dependent upon whether they had functioning or non-functioning NET, clinical benefit and allocation following randomisation.
Pre-assignment details
Overall, 64 subjects were screened, 7 were screening failures of which 5 subjects did not meet the entry criteria. 57 subjects were assigned to receive treatment in the baseline population.
Participants by arm
| Arm | Count |
|---|---|
| Combination Phase All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months.
Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m\^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m\^2 per day from cycle 2 to cycle 6. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Combination Phase | Adverse Event | 10 | 0 | 0 | 0 |
| Combination Phase | Did not meet inclusion criteria | 1 | 0 | 0 | 0 |
| Combination Phase | Disease Progression | 6 | 0 | 0 | 0 |
| Combination Phase | Protocol Violation | 1 | 0 | 0 | 0 |
| Combination Phase | Withdrawal by Subject | 2 | 0 | 0 | 0 |
| Maintenance Phase | Adverse Event | 0 | 0 | 1 | 2 |
| Maintenance Phase | Disease progression | 0 | 3 | 4 | 3 |
Baseline characteristics
| Characteristic | Combination Phase |
|---|---|
| Age, Continuous | 63.1 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native. | 0 Participants |
| Race (NIH/OMB) Asian. | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) Hispanic or Latino | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander. | 0 Participants |
| Race (NIH/OMB) White | 57 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 57 | 1 / 11 | 1 / 14 | 1 / 12 |
| other Total, other adverse events | 52 / 57 | 9 / 11 | 13 / 14 | 11 / 12 |
| serious Total, serious adverse events | 17 / 57 | 3 / 11 | 4 / 14 | 4 / 12 |
Outcome results
Primary
Disease Control Rate (DCR) After 6 Months
All tumour assessments were performed using the Response Evaluation Criteria In Solid Tumours (RECIST) criteria (1.1). Computer Tomography (CT-scan) or Magnetic Resonance Imaging (MRI) could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at weeks 12, 24 and at early withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression. The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment and was described in the ITT population along with its 95% Confidence Interval (CI) and was compared to 45% with an exact binomial proportion test. The Last Observation Carried Forward (LOCF) method was used to replace missing assessments at the end of the combination phase.
Time frame: 6 months
Population: The ITT population is all subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Phase | Disease Control Rate (DCR) After 6 Months | 73.5 percentage of subjects |
Secondary
DCR After 12 Months
All tumour assessments were performed using the RECIST criteria (1.1). CT-scan or MRI could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at baseline, weeks 12, 24, 36, 48 (end of study) and at study withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression. The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months combination treatment followed by either 6 months of lanreotide ATG 120 mg maintenance treatment or no treatment. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test. The LOCF method was used to replace missing assessments at the end of the maintenance phase.
Time frame: 12 months
Population: The ITT population is all subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Combination Phase | DCR After 12 Months | 54.5 percentage of subjects |
| Maintenance Phase - Non-functioning NET, Lanreotide | DCR After 12 Months | 71.4 percentage of subjects |
| Maintenance Phase - Non-functioning NET, No Treatment | DCR After 12 Months | 41.7 percentage of subjects |
Secondary
DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months
In all subjects whose tumour tissue was available, MGMT expression/methylation and SSTR expression was analysed. After 6 months, the DCR (SD+PR+CR) by MGMT methylation and expression and by SSTR 2a and SSTR 5 expression was evaluated. DCR in response to MGMT methylation and expression results are presented. SSTR 2a and SSTR 5 expression is categorised as: No Receptors, Cytoplasmatic Expression (CE), Focal Expression (FE), Complete Circumferent Membrane Expression (CCME). The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment within each methylation/expression category. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test.
Time frame: 6 months
Population: Percentages are based on the number of subjects in the ITT population and with data available for analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | MGMT Methylation | 100.0 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | MGMT No methylation | 84.6 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | MGMT Expression | 90.9 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | MGMT No expression | 70.0 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | SSTR 2a FE | 86.7 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | SSTR 2a CCME | 72.7 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | SSTR 5 - No Receptors | 75.0 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | SSTR 5 CE | 100.0 percentage of subjects |
| Combination Phase | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months | SSTR 5 FE | 81.8 percentage of subjects |
Secondary
Duration of Response (DoR) Within 12 Months
The DoR is an estimation of the time from first documented objective response (CR or PR) to the first date of progressive disease (PD) or death due to disease progression for subjects who experienced an objective response within the first 12 months of treatment (combination and maintenance phases). The Kaplan-Meier method was used to estimate the median DoR and its 95% CI for subjects in the ITT population who had an objective response.
Time frame: 12 months
Population: The ITT population is all treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Phase | Duration of Response (DoR) Within 12 Months | NA months |
Secondary
EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months
Subjects were instructed to complete QLQ-C30 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 48 (end of study) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms.
Time frame: 12 months
Population: Only subjects in the ITT Population with data available at the week 48 time point were analysed. Only subjects with data available for analysis are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Diarrhoea | -40.0 units on a scale | Standard Deviation 36.5 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Global health status | -11.7 units on a scale | Standard Deviation 40.7 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Social functioning | 13.3 units on a scale | Standard Deviation 34.2 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Pain | -13.3 units on a scale | Standard Deviation 32.1 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Cognitive functioning | 3.3 units on a scale | Standard Deviation 24.7 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Role functioning | 3.3 units on a scale | Standard Deviation 29.8 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Financial difficulties | 6.7 units on a scale | Standard Deviation 14.9 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Emotional functioning | 15.0 units on a scale | Standard Deviation 19 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Insomnia | -13.3 units on a scale | Standard Deviation 50.6 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Appetite loss | 0.0 units on a scale | Standard Deviation 23.6 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Dyspnoea | -8.3 units on a scale | Standard Deviation 41.9 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Nausea and vomiting | -10.0 units on a scale | Standard Deviation 14.9 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Constipation | 20.0 units on a scale | Standard Deviation 38 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Physical functioning | 8.0 units on a scale | Standard Deviation 22.8 |
| Combination Phase | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Fatigue | -22.2 units on a scale | Standard Deviation 30.4 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Appetite loss | 0.0 units on a scale | Standard Deviation 39.8 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Dyspnoea | 4.2 units on a scale | Standard Deviation 33 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Insomnia | -8.3 units on a scale | Standard Deviation 34.5 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Financial difficulties | 4.2 units on a scale | Standard Deviation 27.8 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Constipation | -4.2 units on a scale | Standard Deviation 11.8 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Diarrhoea | 8.3 units on a scale | Standard Deviation 15.4 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Physical functioning | -12.5 units on a scale | Standard Deviation 17.6 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Role functioning | -2.1 units on a scale | Standard Deviation 20.8 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Emotional functioning | -6.2 units on a scale | Standard Deviation 20.3 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Cognitive functioning | -2.1 units on a scale | Standard Deviation 20.8 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Social functioning | -22.9 units on a scale | Standard Deviation 34.4 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Fatigue | -9.7 units on a scale | Standard Deviation 24.1 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Nausea and vomiting | 4.2 units on a scale | Standard Deviation 23.1 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Pain | 4.2 units on a scale | Standard Deviation 24.8 |
| Maintenance Phase - Non-functioning NET, Lanreotide | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Global health status | -3.1 units on a scale | Standard Deviation 10.9 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Pain | 9.5 units on a scale | Standard Deviation 23.3 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Social functioning | -4.8 units on a scale | Standard Deviation 15.9 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Constipation | -4.8 units on a scale | Standard Deviation 35.6 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Insomnia | 16.7 units on a scale | Standard Deviation 27.9 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Fatigue | 4.8 units on a scale | Standard Deviation 16.8 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Appetite loss | 14.3 units on a scale | Standard Deviation 17.8 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Dyspnoea | 9.5 units on a scale | Standard Deviation 16.3 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Nausea and vomiting | 2.4 units on a scale | Standard Deviation 6.3 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Role functioning | -7.1 units on a scale | Standard Deviation 13.1 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Diarrhoea | 0.0 units on a scale | Standard Deviation 27.2 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Emotional functioning | -6.0 units on a scale | Standard Deviation 12.5 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Physical functioning | -11.4 units on a scale | Standard Deviation 13.7 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Global health status | -7.1 units on a scale | Standard Deviation 15.5 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Cognitive functioning | 2.4 units on a scale | Standard Deviation 6.3 |
| Maintenance Phase - Non-functioning NET, No Treatment | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months | Financial difficulties | 9.5 units on a scale | Standard Deviation 25.2 |
Secondary
European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months
Subjects were instructed to complete the QLQ-C30 questionnaire at baseline, weeks 12, 24 or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 24 (end of the combination phase) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms.
Time frame: 6 months
Population: Only subjects in the ITT Population with data available at the week 24 time point were analysed. Only subjects with data available for analysis are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Global health status | -4.9 units on a scale | Standard Deviation 18.2 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Physical functioning | -9.6 units on a scale | Standard Deviation 19.4 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Role functioning | -8.3 units on a scale | Standard Deviation 27.6 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Emotional functioning | -4.7 units on a scale | Standard Deviation 17.7 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Cognitive functioning | -5.9 units on a scale | Standard Deviation 15.8 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Social functioning | -11.8 units on a scale | Standard Deviation 23.8 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Fatigue | 6.9 units on a scale | Standard Deviation 20.1 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Nausea and vomiting | 6.9 units on a scale | Standard Deviation 14.9 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Pain | -1.0 units on a scale | Standard Deviation 31 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Dyspnoea | 12.7 units on a scale | Standard Deviation 30.7 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Insomnia | 0.0 units on a scale | Standard Deviation 34.9 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Appetite loss | 2.0 units on a scale | Standard Deviation 24.5 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Constipation | 6.9 units on a scale | Standard Deviation 33.6 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Diarrhoea | -3.9 units on a scale | Standard Deviation 34.6 |
| Combination Phase | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months | Financial difficulties | 2.9 units on a scale | Standard Deviation 17.1 |
Secondary
Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months
Lanreotide ATG levels were measured in a subset of subjects to evaluate if temozolomide co-treatment had an impact on lanreotide serum concentration over a 12 month period. Blood samples were collected for the determination of lanreotide ATG in serum at baseline, weeks 4, 12, 24 and 48 (end of study). The concentrations of lanreotide ATG in serum were determined by a validated radioimmunoassay analysis method with a lower limit of quantitation of 0.08 nanograms \[ng\]/mL). Serum concentrations of lanreotide ATG at each of the time points in the combination and maintenance phase are presented. Only subjects with data available for analysis are presented.
Time frame: Baseline (week 1) and weeks 4, 12, 24 and 48
Population: PK analysis was performed using the valid PK population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Phase | Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months | Baseline | 0.44 ng/mL | Standard Deviation 1.22 |
| Combination Phase | Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months | Week 4 | 2.45 ng/mL | Standard Deviation 1.16 |
| Combination Phase | Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months | Week 12 | 5.06 ng/mL | Standard Deviation 3.01 |
| Combination Phase | Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months | Week 24 | 5.83 ng/mL | Standard Deviation 1.93 |
| Combination Phase | Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months | Week 48 | 3.68 ng/mL | Standard Deviation 3.36 |
Secondary
Progression-Free Survival (PFS) Within 12 Months
PFS was defined as the time from the date of treatment start to the date of the first documented disease progression or death due to any cause within the first 12 months of treatment. If a subject had not progressed or died after 12 months of treatment or when any further anti-neoplastic therapy was received, PFS was censored at the time of the last tumour assessment before the analysis cut-off date or the anti-neoplastic therapy date. A Kaplan-Meier estimate of the PFS was calculated to determine the number of subjects at risk. Median PFS time (50% of subjects who would not progress or die) of the ITT population is presented along with 95 % CI.
Time frame: 12 months
Population: The ITT population is all treated subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Phase | Progression-Free Survival (PFS) Within 12 Months | 11.1 months |
Secondary
QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months
Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Answers were converted into grading scale, with values between 0 and 100. Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 48 (end of study) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms.
Time frame: 12 months
Population: Only subjects in the ITT Population with data available at the week 48 time point were analysed. Only subjects with data available for analysis are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Endocrine symptoms | -13.3 units on a scale | Standard Deviation 21.4 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | G.I. symptoms | -4.0 units on a scale | Standard Deviation 21.9 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Treatment related symptoms | 0.0 units on a scale | Standard Deviation 0 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Social function | -6.7 units on a scale | Standard Deviation 23 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Disease related worries | -6.7 units on a scale | Standard Deviation 36.5 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Muscle/bone pain symptoms | -6.7 units on a scale | Standard Deviation 14.9 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Body image | 0.0 units on a scale | Standard Deviation 23.6 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Weight gain | -20.0 units on a scale | Standard Deviation 29.8 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Information/communication function | 0.0 units on a scale | Standard Deviation 70.7 |
| Combination Phase | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Sexual function | 0.0 units on a scale | Standard Deviation 0 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Endocrine symptoms | -5.6 units on a scale | Standard Deviation 19.7 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Muscle/bone pain symptoms | 4.2 units on a scale | Standard Deviation 33 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Disease related worries | 1.4 units on a scale | Standard Deviation 15.1 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | G.I. symptoms | 0.0 units on a scale | Standard Deviation 19.2 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Sexual function | 0.0 units on a scale | Standard Deviation 0 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Weight gain | 9.5 units on a scale | Standard Deviation 25.2 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Treatment related symptoms | -11.1 units on a scale | Standard Deviation 34.7 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Body image | 4.2 units on a scale | Standard Deviation 27.8 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Social function | 9.7 units on a scale | Standard Deviation 20.9 |
| Maintenance Phase - Non-functioning NET, Lanreotide | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Information/communication function | 0.0 units on a scale | Standard Deviation 17.8 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Body image | 4.8 units on a scale | Standard Deviation 12.6 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Disease related worries | -3.2 units on a scale | Standard Deviation 30.6 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Muscle/bone pain symptoms | 4.8 units on a scale | Standard Deviation 30 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Information/communication function | -4.8 units on a scale | Standard Deviation 12.6 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Social function | -6.3 units on a scale | Standard Deviation 16.8 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Endocrine symptoms | 1.6 units on a scale | Standard Deviation 4.2 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Sexual function | 0.0 units on a scale | Standard Deviation 0 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | G.I. symptoms | 6.7 units on a scale | Standard Deviation 7.7 |
| Maintenance Phase - Non-functioning NET, No Treatment | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months | Weight gain | -9.5 units on a scale | Standard Deviation 56.8 |
Secondary
Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months
Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24 or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 24 (end of combination phase) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms.
Time frame: 6 months
Population: Only subjects in the ITT Population with data available at the week 24 time point were analysed. Only subjects with data available for analysis are presented.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Muscle/bone pain symptoms | 1.0 Units on a scale | Standard Deviation 37.1 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Body image | 0.0 Units on a scale | Standard Deviation 23.2 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Weight gain | -11.8 Units on a scale | Standard Deviation 30.5 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Information/communication function | -9.4 Units on a scale | Standard Deviation 22.8 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Sexual function | -4.8 Units on a scale | Standard Deviation 17.8 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Endocrine symptoms | -1.0 Units on a scale | Standard Deviation 13.5 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Gastrointestinal (G.I.) symptoms | 5.7 Units on a scale | Standard Deviation 14 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Treatment related symptoms | 3.6 Units on a scale | Standard Deviation 30.1 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Social function | 2.3 Units on a scale | Standard Deviation 25.3 |
| Combination Phase | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months | Disease related worries | 1.6 Units on a scale | Standard Deviation 27.1 |
Secondary
The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months
Urine samples for 5-HIAA urinary tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and early withdrawal. Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline). The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.
Time frame: 12 months
Population: Subjects in the ITT population with functioning NET.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 24 - Progression | 6 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 24 - Response | 3 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 24 - Not evaluable | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 24 - Missing | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 36 - Progression | 3 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 36 - Response | 3 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 36 - Not evaluable | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 36 - Missing | 3 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 48 - Progression | 4 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 48 - Response | 2 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 48 - Not evaluable | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Week 48 - Missing | 2 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Early Withdrawal - Progression | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Early Withdrawal - Response | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Early Withdrawal - Not evaluable | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months | Early Withdrawal - Missing | 3 Participants |
Secondary
The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months
Urine samples for 5-HIAA urinary tumour marker analysis were taken at at baseline, weeks 12, 24and early withdrawal. Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline). The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.
Time frame: 6 months
Population: Subjects in the ITT population with functioning NET.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Early Withdrawal - Progression | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 12 - Progression | 4 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 12 - Response | 6 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 12 - Not evaluable | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 12 - Missing | 6 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 24 - Progression | 6 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 24 - Response | 3 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 24 - Not evaluable | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Week 24 - Missing | 3 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Early Withdrawal - Response | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Early Withdrawal - Not Evaluable | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months | Early Withdrawal - Missing | 7 Participants |
Secondary
The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months
Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and at early withdrawal. The biochemical response after 12 months combination and maintenance treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 mcg/L). Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥50 % compared to the baseline CgA), SD (decrease \< 50% or an increase ≤ 25% compared to the baseline CgA) or PD (defined as an increase ≥ 25%, compared to the baseline CgA). The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline.
Time frame: 12 months
Population: Subjects in the ITT population with abnormal CgA levels at baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - Missing | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - Missing | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - SD | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - PD | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - PR | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - PD | 2 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - SD | 2 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - PR | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - SD | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - PR | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - Missing | 2 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - PD | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - PD | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - SD | 3 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - PR | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - Missing | 0 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - PR | 2 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - Missing | 0 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - PD | 1 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - PD | 2 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - SD | 0 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - PR | 3 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - PR | 1 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - Missing | 1 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - Missing | 0 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - Missing | 1 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - PD | 1 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - SD | 4 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - PD | 1 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - PR | 1 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - SD | 2 Participants |
| Maintenance Phase - Non-functioning NET, Lanreotide | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - SD | 4 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - Missing | 0 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - Missing | 0 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - PD | 2 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - PD | 2 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - SD | 2 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - PR | 3 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 24 - Missing | 2 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - PD | 3 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - SD | 2 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 36 - PR | 4 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - SD | 3 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - PR | 1 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Week 48 - Missing | 0 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - PD | 1 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - SD | 0 Participants |
| Maintenance Phase - Non-functioning NET, No Treatment | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months | Early Withdrawal - PR | 1 Participants |
Secondary
The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months
Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24 and at early withdrawal. The biochemical response after 6 months combination treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 micrograms/litre \[mcg/L\]). Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥ 50%, compared to the baseline CgA), SD (decrease \< 50 % or an increase ≤25%, compared to the baseline CgA) or PD (defined as an increase ≥25 %, compared to the baseline CgA). The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline.
Time frame: 6 months
Population: Subjects in the ITT population with abnormal CgA levels at baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 12- PD | 8 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 12 - SD | 15 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 12- PR | 10 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 12 - Missing | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 24 - PD | 5 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 24 - SD | 9 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 24 - PR | 7 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Week 24 - Missing | 0 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Early Withdrawal - PD | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Early Withdrawal - SD | 2 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Early Withdrawal - PR | 1 Participants |
| Combination Phase | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months | Early Withdrawal - Missing | 14 Participants |
Secondary
The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase
Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline. Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing. The number of subjects in each response category at week 48 (end of study) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.
Time frame: 12 months
Population: Subjects in the ITT population with functioning NET.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Diarrhoea - Reduction | 4 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Diarrhoea - Increase | 1 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Diarrhoea - Stability | 3 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Diarrhoea - Missing | 3 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Flushing - Increase | 3 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Flushing - Stability | 3 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Flushing - Missing | 3 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase | Flushing - Reduction | 2 Participants |
Secondary
The Number of Subjects With a Symptomatic Response After 6 Months
Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline. Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing. The number of subjects in each response category at week 24 (end of the combination phase) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET.
Time frame: 6 months
Population: Subjects in the ITT population with functioning NET.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Diarrhoea - Reduction | 4 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Diarrhoea - Increase | 2 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Diarrhoea - Stability | 5 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Diarrhoea - Missing | 6 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Flushing - Reduction | 4 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Flushing - Increase | 4 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Flushing - Stability | 3 Participants |
| Combination Phase | The Number of Subjects With a Symptomatic Response After 6 Months | Flushing - Missing | 6 Participants |
Secondary
Time To Response (TtR) Within 12 Months
TtR was defined as the time from the date of treatment start to the date of the first documented objective response (CR or PR) within the first 12 months of treatment (combination and maintenance phases). A Kaplan Meier estimate of the TtR survival function was constructed. The Kaplan-Meier method was used to estimate the median TtR and its 95% CI for subjects in the ITT population (50% of subjects were expected to have a CR or PR at this time).
Time frame: 12 months
Population: The ITT population is all treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Combination Phase | Time To Response (TtR) Within 12 Months | NA months |