SONNET: Combination of Lanreotide Autogel 120mg and Temozolomide in Progressive GEP-NET
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Lanreotide Autogel 120mg & Temozolomide Combination phase for first 6 months: Lanreotide Autogel 120 mg and Temozolomide. Followed by either 6 months Lanreotide Autogel 120 mg maintenance or 6 months of no treatment. |
Drug: Lanreotide Autogel 120 mg
Lanreotide Autogel 120 mg subcutaneous (s.c) - injection, every 28 days (+/-2 days).
Drug: Temozolomide (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.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
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)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Vienna General Hospital | Vienna | Austria | 1090 | |
| 2 | Zentralklinik Bad Berka | Bad Berka | Germany | 99437 | |
| 3 | Charité University Hospital | Berlin | Germany | 13353 | |
| 4 | University Hospital Essen | Essen | Germany | 45122 | |
| 5 | ENDOC Hamburg | Hamburg | Germany | 20357 | |
| 6 | Oncological Center Leer | Leer | Germany | 26789 | |
| 7 | University Hospital Mainz | Mainz | Germany | 55131 | |
| 8 | University Hospital Mannheim | Mannheim | Germany | 68167 | |
| 9 | University Hospital Marburg | Marburg | Germany | 35043 | |
| 10 | University Hospital Munich | Munich | Germany | 81377 |
Sponsors and Collaborators
- Ipsen
Investigators
- Study Director: Ipsen Medical Director, Ipsen
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- A-94-52030-268
- 2013-001697-17
Study Results
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 Detail | Overall, 64 subjects were screened, 7 were screening failures of which 5 subjects did not meet the entry criteria. 57 subjects were assigned to receive treatment in the baseline population. |
| Arm/Group Title | Combination Phase | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment |
|---|---|---|---|---|
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6. | In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24. |
| Period Title: Combination Phase | ||||
| STARTED | 57 | 0 | 0 | 0 |
| COMPLETED | 37 | 0 | 0 | 0 |
| NOT COMPLETED | 20 | 0 | 0 | 0 |
| Period Title: Combination Phase | ||||
| STARTED | 0 | 11 | 14 | 12 |
| COMPLETED | 0 | 8 | 9 | 7 |
| NOT COMPLETED | 0 | 3 | 5 | 5 |
Baseline Characteristics
| Arm/Group Title | Combination Phase |
|---|---|
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6. |
| Overall Participants | 57 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
63.1
(11.0)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
24
42.1%
|
| Male |
33
57.9%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native. |
0
0%
|
| Asian. |
0
0%
|
| Black or African American |
0
0%
|
| Hispanic or Latino |
0
0%
|
| Native Hawaiian or Other Pacific Islander. |
0
0%
|
| White |
57
100%
|
Outcome Measures
| Title | Disease Control Rate (DCR) After 6 Months |
|---|---|
| Description | All tumour assessments were performed using the Response Evaluation Criteria In Solid Tumours (RECIST) criteria (1.1). Computer Tomography (CT-scan) or Magnetic Resonance Imaging (MRI) could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at weeks 12, 24 and at early withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression. The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment and was described in the ITT population along with its 95% Confidence Interval (CI) and was compared to 45% with an exact binomial proportion test. The Last Observation Carried Forward (LOCF) method was used to replace missing assessments at the end of the combination phase. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population is all subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter. |
| Arm/Group Title | Combination Phase |
|---|---|
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6. |
| Measure Participants | 49 |
| Number (95% Confidence Interval) [percentage of subjects] |
73.5
|
| Title | DCR After 12 Months |
|---|---|
| Description | All tumour assessments were performed using the RECIST criteria (1.1). CT-scan or MRI could be used for as method of tumour measurement and the same method of tumour measurement was used throughout the study for each subject. CT scans/MRI were performed at screening or baseline visit then at baseline, weeks 12, 24, 36, 48 (end of study) and at study withdrawal or at anytime during the study in the case of any clinical or biological signs of tumour progression. The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months combination treatment followed by either 6 months of lanreotide ATG 120 mg maintenance treatment or no treatment. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test. The LOCF method was used to replace missing assessments at the end of the maintenance phase. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population is all subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter. |
| Arm/Group Title | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment |
|---|---|---|---|
| Arm/Group Description | In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24. |
| Measure Participants | 11 | 14 | 12 |
| Number (95% Confidence Interval) [percentage of subjects] |
54.5
|
71.4
|
41.7
|
| Title | Progression-Free Survival (PFS) Within 12 Months |
|---|---|
| Description | PFS was defined as the time from the date of treatment start to the date of the first documented disease progression or death due to any cause within the first 12 months of treatment. If a subject had not progressed or died after 12 months of treatment or when any further anti-neoplastic therapy was received, PFS was censored at the time of the last tumour assessment before the analysis cut-off date or the anti-neoplastic therapy date. A Kaplan-Meier estimate of the PFS was calculated to determine the number of subjects at risk. Median PFS time (50% of subjects who would not progress or die) of the ITT population is presented along with 95 % CI. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population is all treated subjects that had at least one baseline and at least one post baseline assessment of the primary efficacy parameter. |
| Arm/Group Title | Intention-to-treat (ITT) Population |
|---|---|
| Arm/Group Description | All treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter. |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [months] |
11.1
|
| Title | Time To Response (TtR) Within 12 Months |
|---|---|
| Description | TtR was defined as the time from the date of treatment start to the date of the first documented objective response (CR or PR) within the first 12 months of treatment (combination and maintenance phases). A Kaplan Meier estimate of the TtR survival function was constructed. The Kaplan-Meier method was used to estimate the median TtR and its 95% CI for subjects in the ITT population (50% of subjects were expected to have a CR or PR at this time). |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population is all treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter |
| Arm/Group Title | Intention-to-treat (ITT) Population |
|---|---|
| Arm/Group Description | All treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter. |
| Measure Participants | 49 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | Duration of Response (DoR) Within 12 Months |
|---|---|
| Description | The DoR is an estimation of the time from first documented objective response (CR or PR) to the first date of progressive disease (PD) or death due to disease progression for subjects who experienced an objective response within the first 12 months of treatment (combination and maintenance phases). The Kaplan-Meier method was used to estimate the median DoR and its 95% CI for subjects in the ITT population who had an objective response. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The ITT population is all treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter. |
| Arm/Group Title | Intention-to-treat (ITT) Population |
|---|---|
| Arm/Group Description | All treated subjects having at least one baseline and at least one post baseline assessment of the primary efficacy parameter. |
| Measure Participants | 6 |
| Median (95% Confidence Interval) [months] |
NA
|
| Title | The Number of Subjects With a Biochemical Response Using Chromogranin-A (CgA) Levels After 6 Months |
|---|---|
| Description | Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24 and at early withdrawal. The biochemical response after 6 months combination treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 micrograms/litre [mcg/L]). Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥ 50%, compared to the baseline CgA), SD (decrease < 50 % or an increase ≤25%, compared to the baseline CgA) or PD (defined as an increase ≥25 %, compared to the baseline CgA). The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the ITT population with abnormal CgA levels at baseline. |
| Arm/Group Title | Combination Phase |
|---|---|
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6. |
| Measure Participants | 34 |
| Week 12- PD |
8
14%
|
| Week 12 - SD |
15
26.3%
|
| Week 12- PR |
10
17.5%
|
| Week 12 - Missing |
1
1.8%
|
| Week 24 - PD |
5
8.8%
|
| Week 24 - SD |
9
15.8%
|
| Week 24 - PR |
7
12.3%
|
| Week 24 - Missing |
0
0%
|
| Early Withdrawal - PD |
1
1.8%
|
| Early Withdrawal - SD |
2
3.5%
|
| Early Withdrawal - PR |
1
1.8%
|
| Early Withdrawal - Missing |
14
24.6%
|
| Title | The Number of Subjects With a Biochemical Response Using CgA Levels After 12 Months |
|---|---|
| Description | Blood samples for CgA blood tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and at early withdrawal. The biochemical response after 12 months combination and maintenance treatment was estimated for subjects with abnormal CgA levels at baseline. Abnormal CgA levels were defined as above the upper limit of normal range (≥100 mcg/L). Biochemical response based on CgA levels was categorised as: PR (decrease of CgA ≥50 % compared to the baseline CgA), SD (decrease < 50% or an increase ≤ 25% compared to the baseline CgA) or PD (defined as an increase ≥ 25%, compared to the baseline CgA). The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population who had abnormal CgA at baseline. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the ITT population with abnormal CgA levels at baseline. |
| Arm/Group Title | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment |
|---|---|---|---|
| Arm/Group Description | In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24. |
| Measure Participants | 5 | 9 | 9 |
| Week 24 - PD |
2
3.5%
|
1
NaN
|
2
NaN
|
| Week 24 - SD |
3
5.3%
|
4
NaN
|
2
NaN
|
| Week 24 - PR |
0
0%
|
3
NaN
|
3
NaN
|
| Week 24 - Missing |
0
0%
|
1
NaN
|
2
NaN
|
| Week 36 - PD |
1
1.8%
|
1
NaN
|
3
NaN
|
| Week 36 - SD |
2
3.5%
|
4
NaN
|
2
NaN
|
| Week 36 - PR |
0
0%
|
1
NaN
|
4
NaN
|
| Week 36 - Missing |
0
0%
|
1
NaN
|
0
NaN
|
| Week 48 - PD |
1
1.8%
|
1
NaN
|
2
NaN
|
| Week 48 - SD |
0
0%
|
2
NaN
|
3
NaN
|
| Week 48 - PR |
1
1.8%
|
2
NaN
|
1
NaN
|
| Week 48 - Missing |
0
0%
|
0
NaN
|
0
NaN
|
| Early Withdrawal - PD |
1
1.8%
|
2
NaN
|
1
NaN
|
| Early Withdrawal - SD |
0
0%
|
0
NaN
|
0
NaN
|
| Early Withdrawal - PR |
0
0%
|
1
NaN
|
1
NaN
|
| Early Withdrawal - Missing |
2
3.5%
|
0
NaN
|
0
NaN
|
| Title | The Number of Subjects With a Biochemical Response Using 5-Hydroxy-Indol-Amino-Acid (HIAA) Levels After 6 Months |
|---|---|
| Description | Urine samples for 5-HIAA urinary tumour marker analysis were taken at at baseline, weeks 12, 24and early withdrawal. Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline). The number of subjects in each response category at each time point in the combination phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the ITT population with functioning NET. |
| Arm/Group Title | Combination Phase - Functioning NET |
|---|---|
| Arm/Group Description | All subjects in the combination phase who were categorised at baseline as having functioning NET. |
| Measure Participants | 17 |
| Week 12 - Progression |
4
7%
|
| Week 12 - Response |
6
10.5%
|
| Week 12 - Not evaluable |
1
1.8%
|
| Week 12 - Missing |
6
10.5%
|
| Week 24 - Progression |
6
10.5%
|
| Week 24 - Response |
3
5.3%
|
| Week 24 - Not evaluable |
1
1.8%
|
| Week 24 - Missing |
3
5.3%
|
| Early Withdrawal - Progression |
0
0%
|
| Early Withdrawal - Response |
1
1.8%
|
| Early Withdrawal - Not Evaluable |
0
0%
|
| Early Withdrawal - Missing |
7
12.3%
|
| Title | The Number of Subjects With a Biochemical Response Using 5-HIAA Levels After 12 Months |
|---|---|
| Description | Urine samples for 5-HIAA urinary tumour marker analysis were taken at baseline, weeks 12, 24, 36, 48 (end of study) and early withdrawal. Biochemical response based on 5-HIAA levels was categorised as: Response (5-HIAA reduction compared to baseline) or Progression (5-HIAA increase compared to baseline). The number of subjects in each response category at each time point in the maintenance phase is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the ITT population with functioning NET. |
| Arm/Group Title | Maintenance Phase - Functioning NET, Lanreotide |
|---|---|
| Arm/Group Description | In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. |
| Measure Participants | 11 |
| Week 24 - Progression |
6
10.5%
|
| Week 24 - Response |
3
5.3%
|
| Week 24 - Not evaluable |
1
1.8%
|
| Week 24 - Missing |
1
1.8%
|
| Week 36 - Progression |
3
5.3%
|
| Week 36 - Response |
3
5.3%
|
| Week 36 - Not evaluable |
0
0%
|
| Week 36 - Missing |
3
5.3%
|
| Week 48 - Progression |
4
7%
|
| Week 48 - Response |
2
3.5%
|
| Week 48 - Not evaluable |
0
0%
|
| Week 48 - Missing |
2
3.5%
|
| Early Withdrawal - Progression |
0
0%
|
| Early Withdrawal - Response |
0
0%
|
| Early Withdrawal - Not evaluable |
0
0%
|
| Early Withdrawal - Missing |
3
5.3%
|
| Title | The Number of Subjects With a Symptomatic Response After 6 Months |
|---|---|
| Description | Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline. Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing. The number of subjects in each response category at week 24 (end of the combination phase) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the ITT population with functioning NET. |
| Arm/Group Title | Combination Phase - Functioning NET |
|---|---|
| Arm/Group Description | All subjects in the combination phase who were categorised at baseline as having functioning NET. |
| Measure Participants | 17 |
| Diarrhoea - Reduction |
4
7%
|
| Diarrhoea - Increase |
2
3.5%
|
| Diarrhoea - Stability |
5
8.8%
|
| Diarrhoea - Missing |
6
10.5%
|
| Flushing - Reduction |
4
7%
|
| Flushing - Increase |
4
7%
|
| Flushing - Stability |
3
5.3%
|
| Flushing - Missing |
6
10.5%
|
| Title | The Number of Subjects With a Symptomatic Response After 12 Months - Maintenance Phase |
|---|---|
| Description | Symptomatic response was evaluated as absolute change from baseline in the number of episodes of the lead symptoms (i.e. diarrhoea and flushing) using the mean of the last 3 days before the visit, at each visit, as compared to baseline. Symptomatic responses were categorised as: Reduction, Increase or Stability of occurrences of diarrhoea / Reduction, Increase or Stability of occurrences of flushing. The number of subjects in each response category at week 48 (end of study) is presented. Analysis was only carried out on subjects in the ITT population with functioning NET. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subjects in the ITT population with functioning NET. |
| Arm/Group Title | Maintenance Phase - Functioning NET, Lanreotide |
|---|---|
| Arm/Group Description | In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. |
| Measure Participants | 11 |
| Diarrhoea - Reduction |
4
7%
|
| Diarrhoea - Increase |
1
1.8%
|
| Diarrhoea - Stability |
3
5.3%
|
| Diarrhoea - Missing |
3
5.3%
|
| Flushing - Reduction |
2
3.5%
|
| Flushing - Increase |
3
5.3%
|
| Flushing - Stability |
3
5.3%
|
| Flushing - Missing |
3
5.3%
|
| Title | European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life (QoL) Core 30 Questionnaire (QLQ-C30): Mean Change From Baseline at 6 Months |
|---|---|
| Description | Subjects were instructed to complete the QLQ-C30 questionnaire at baseline, weeks 12, 24 or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 24 (end of the combination phase) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects in the ITT Population with data available at the week 24 time point were analysed. Only subjects with data available for analysis are presented. |
| Arm/Group Title | Combination Phase |
|---|---|
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6. |
| Measure Participants | 34 |
| Global health status |
-4.9
(18.2)
|
| Physical functioning |
-9.6
(19.4)
|
| Role functioning |
-8.3
(27.6)
|
| Emotional functioning |
-4.7
(17.7)
|
| Cognitive functioning |
-5.9
(15.8)
|
| Social functioning |
-11.8
(23.8)
|
| Fatigue |
6.9
(20.1)
|
| Nausea and vomiting |
6.9
(14.9)
|
| Pain |
-1.0
(31.0)
|
| Dyspnoea |
12.7
(30.7)
|
| Insomnia |
0.0
(34.9)
|
| Appetite loss |
2.0
(24.5)
|
| Constipation |
6.9
(33.6)
|
| Diarrhoea |
-3.9
(34.6)
|
| Financial difficulties |
2.9
(17.1)
|
| Title | EORTC QoL Questionnaire QLQ-C30: Mean Change From Baseline at 12 Months |
|---|---|
| Description | Subjects were instructed to complete QLQ-C30 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. The first 28 questions used a 4-point scale (1=not at all, 2=a little, 3=quite a bit, 4=very much) for evaluating 5 functional scales (physical, role, emotional, cognitive, social), 3 symptom scales (fatigue, nausea/vomiting, pain) & 6 other single items. The last 2 questions represented subject's assessment of overall health & quality of life, coded on a 7-point scale (1=very poor to 7=excellent). The mean change from baseline at week 48 (end of study) is presented for global health status (scoring of questions 29 & 30) and 5 functional scales, 3 symptom scales and other single items (scoring of questions 1 to 28). Each individual subscore was transformed to range from 0 to 100. A higher score represents a higher level response. Thus, a better QoL/a better level of functioning/a worse level of symptoms. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects in the ITT Population with data available at the week 48 time point were analysed. Only subjects with data available for analysis are presented. |
| Arm/Group Title | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment |
|---|---|---|---|
| Arm/Group Description | In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24. |
| Measure Participants | 5 | 8 | 7 |
| Global health status |
-11.7
(40.7)
|
-3.1
(10.9)
|
-7.1
(15.5)
|
| Physical functioning |
8.0
(22.8)
|
-12.5
(17.6)
|
-11.4
(13.7)
|
| Role functioning |
3.3
(29.8)
|
-2.1
(20.8)
|
-7.1
(13.1)
|
| Emotional functioning |
15.0
(19.0)
|
-6.2
(20.3)
|
-6.0
(12.5)
|
| Cognitive functioning |
3.3
(24.7)
|
-2.1
(20.8)
|
2.4
(6.3)
|
| Social functioning |
13.3
(34.2)
|
-22.9
(34.4)
|
-4.8
(15.9)
|
| Fatigue |
-22.2
(30.4)
|
-9.7
(24.1)
|
4.8
(16.8)
|
| Nausea and vomiting |
-10.0
(14.9)
|
4.2
(23.1)
|
2.4
(6.3)
|
| Pain |
-13.3
(32.1)
|
4.2
(24.8)
|
9.5
(23.3)
|
| Dyspnoea |
-8.3
(41.9)
|
4.2
(33.0)
|
9.5
(16.3)
|
| Insomnia |
-13.3
(50.6)
|
-8.3
(34.5)
|
16.7
(27.9)
|
| Appetite loss |
0.0
(23.6)
|
0.0
(39.8)
|
14.3
(17.8)
|
| Constipation |
20.0
(38.0)
|
-4.2
(11.8)
|
-4.8
(35.6)
|
| Diarrhoea |
-40.0
(36.5)
|
8.3
(15.4)
|
0.0
(27.2)
|
| Financial difficulties |
6.7
(14.9)
|
4.2
(27.8)
|
9.5
(25.2)
|
| Title | Quality of Life Gastrointestinal Neuroendocrine Tumour 21 Questionnaire (QLQ-GI.NET21): Mean Change From Baseline at 6 Months |
|---|---|
| Description | Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24 or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 24 (end of combination phase) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects in the ITT Population with data available at the week 24 time point were analysed. Only subjects with data available for analysis are presented. |
| Arm/Group Title | Combination Phase |
|---|---|
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6. |
| Measure Participants | 34 |
| Endocrine symptoms |
-1.0
(13.5)
|
| Gastrointestinal (G.I.) symptoms |
5.7
(14.0)
|
| Treatment related symptoms |
3.6
(30.1)
|
| Social function |
2.3
(25.3)
|
| Disease related worries |
1.6
(27.1)
|
| Muscle/bone pain symptoms |
1.0
(37.1)
|
| Body image |
0.0
(23.2)
|
| Weight gain |
-11.8
(30.5)
|
| Information/communication function |
-9.4
(22.8)
|
| Sexual function |
-4.8
(17.8)
|
| Title | QoL Questionnaire QLQ-GI.NET21: Mean Change From Baseline at 12 Months |
|---|---|
| Description | Subjects were instructed to complete the QLQ-GI.NET21 questionnaire at baseline, weeks 12, 24, 36, 48 (end of study) or at early withdrawal. It contained 21 questions that used a 4-point scale (1 = Not at all, 2 = A little, 3 = Quite a bit, 4 = Very much) to evaluate 3 defined multi-item symptom scales (endocrine, gastrointestinal and treatment related side effects), 2 single item symptoms (bone/muscle pain and concern about weight loss), 2 psychosocial scales (social function and disease-related worries) and 2 other single items (sexuality and communication). Answers were converted into grading scale, with values between 0 and 100. Each individual subscore was transformed to range from 0 to 100. The mean change from baseline at week 48 (end of study) is presented with a higher score representing a higher level response. Thus, a better level of functioning/a worse level of symptoms. |
| Time Frame | 12 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Only subjects in the ITT Population with data available at the week 48 time point were analysed. Only subjects with data available for analysis are presented. |
| Arm/Group Title | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment |
|---|---|---|---|
| Arm/Group Description | In case of clinical benefit, defined as either complete response (CR), partial response (PR) or stable disease (SD) after the first 6 months combination phase, all subjects with functioning (serotonin producing) NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | After the first 6 months combination phase, subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24. |
| Measure Participants | 5 | 8 | 7 |
| Endocrine symptoms |
-13.3
(21.4)
|
-5.6
(19.7)
|
1.6
(4.2)
|
| G.I. symptoms |
-4.0
(21.9)
|
0.0
(19.2)
|
6.7
(7.7)
|
| Treatment related symptoms |
0.0
(0.0)
|
-11.1
(34.7)
|
|
| Social function |
-6.7
(23.0)
|
9.7
(20.9)
|
-6.3
(16.8)
|
| Disease related worries |
-6.7
(36.5)
|
1.4
(15.1)
|
-3.2
(30.6)
|
| Muscle/bone pain symptoms |
-6.7
(14.9)
|
4.2
(33.0)
|
4.8
(30.0)
|
| Body image |
0.0
(23.6)
|
4.2
(27.8)
|
4.8
(12.6)
|
| Weight gain |
-20.0
(29.8)
|
9.5
(25.2)
|
-9.5
(56.8)
|
| Information/communication function |
0.0
(70.7)
|
0.0
(17.8)
|
-4.8
(12.6)
|
| Sexual function |
0.0
(0.0)
|
0.0
(0.0)
|
0.0
(0.0)
|
| Title | DCR by O6-methylguanine-DNA Methyl-transferase (MGMT) Expression and Methylation and Somatostatin Receptor (SSTR) Expression After 6 Months |
|---|---|
| Description | In all subjects whose tumour tissue was available, MGMT expression/methylation and SSTR expression was analysed. After 6 months, the DCR (SD+PR+CR) by MGMT methylation and expression and by SSTR 2a and SSTR 5 expression was evaluated. DCR in response to MGMT methylation and expression results are presented. SSTR 2a and SSTR 5 expression is categorised as: No Receptors, Cytoplasmatic Expression (CE), Focal Expression (FE), Complete Circumferent Membrane Expression (CCME). The DCR was defined as the proportion of subjects with a response of CR, PR or SD after 6 months of combination treatment within each methylation/expression category. The DCR was described in the ITT population along with its 95% CI and was compared to 45% with an exact binomial proportion test. |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Percentages are based on the number of subjects in the ITT population and with data available for analysis. |
| Arm/Group Title | Combination Phase |
|---|---|
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6 |
| Measure Participants | 49 |
| MGMT Methylation |
100.0
|
| MGMT No methylation |
84.6
|
| MGMT Expression |
90.9
|
| MGMT No expression |
70.0
|
| SSTR 2a FE |
86.7
|
| SSTR 2a CCME |
72.7
|
| SSTR 5 - No Receptors |
75.0
|
| SSTR 5 CE |
100.0
|
| SSTR 5 FE |
81.8
|
| Title | Pharmacokinetic (PK) Results: Lanreotide ATG 120 mg Serum Concentrations Within 12 Months |
|---|---|
| Description | Lanreotide ATG levels were measured in a subset of subjects to evaluate if temozolomide co-treatment had an impact on lanreotide serum concentration over a 12 month period. Blood samples were collected for the determination of lanreotide ATG in serum at baseline, weeks 4, 12, 24 and 48 (end of study). The concentrations of lanreotide ATG in serum were determined by a validated radioimmunoassay analysis method with a lower limit of quantitation of 0.08 nanograms [ng]/mL). Serum concentrations of lanreotide ATG at each of the time points in the combination and maintenance phase are presented. Only subjects with data available for analysis are presented. |
| Time Frame | Baseline (week 1) and weeks 4, 12, 24 and 48 |
Outcome Measure Data
| Analysis Population Description |
|---|
| PK analysis was performed using the valid PK population. |
| Arm/Group Title | PK Subset |
|---|---|
| Arm/Group Description | All subjects for whom PK assessments were performed and with evaluable PK data. |
| Measure Participants | 16 |
| Baseline |
0.44
(1.22)
|
| Week 4 |
2.45
(1.16)
|
| Week 12 |
5.06
(3.01)
|
| Week 24 |
5.83
(1.93)
|
| Week 48 |
3.68
(3.36)
|
Adverse Events
| Time Frame | 13 months (12 month study treatment plus 28 days) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment Emergent Adverse Events (TEAEs) are reported for both the combination and maintenance phases and include events with an onset after the start of study drug treatment to the last intake of study drug plus 28 days. | |||||||
| Arm/Group Title | Combination Phase | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment | ||||
| Arm/Group Description | All subjects received lanreotide ATG 120 mg plus temozolomide in combination for 6 months. Subjects received 1 injection of lanreotide ATG 120 mg and temozolomide capsules for 5 consecutive days, in a 28 day treatment cycle. The temozolomide dose was adapted to the subject body surface area (BSA) and the dose in the 1st treatment cycle was 150 mg/metres squared (m^2) per day. Depending on the safety laboratory values, the temozolomide dose was increased to 200 mg/m^2 per day from cycle 2 to cycle 6. | In case of clinical benefit, defined as either CR, PR or SD, after the first 6 months combination phase all subjects with functioning NET continued to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to continue to receive lanreotide ATG 120 mg for another 6 months. This maintenance phase started with visit 8, week 24. | Following completion of the 6-month combination phase, all subjects with non-functioning NET and clinical benefit were randomised to receive no treatment for 6 months. This maintenance phase started with visit 8, week 24. | ||||
All Cause Mortality |
||||||||
| Combination Phase | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/57 (1.8%) | 1/11 (9.1%) | 1/14 (7.1%) | 1/12 (8.3%) | ||||
Serious Adverse Events |
||||||||
| Combination Phase | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 17/57 (29.8%) | 3/11 (27.3%) | 4/14 (28.6%) | 4/12 (33.3%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Thrombocytopenia | 3/57 (5.3%) | 3 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Leukocytosis | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Cardiac disorders | ||||||||
| Cardiac failure | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Congestive cardiomyopathy | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Tricuspid valve incompetence | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Eye disorders | ||||||||
| Ocular vascular disorder | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Ileus | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Intestinal perforation | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Nausea | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Vomiting | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Abdominal pain | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Ascites | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| General disorders | ||||||||
| Asthenia | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| General physical health deterioration | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Oedema | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Peripheral swelling | 1/57 (1.8%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Multi-organ failure | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pyrexia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hepatobiliary disorders | ||||||||
| Cholangitis | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 1/14 (7.1%) | 2 | 1/12 (8.3%) | 1 |
| Bile duct stenosis | 1/57 (1.8%) | 3 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Hyperbilirubinaemia | 1/57 (1.8%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Jaundice | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||||||
| Pneumonia | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||
| Ankle fracture | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Investigations | ||||||||
| Blood creatinine increased | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| C-reactive protein increased | 1/57 (1.8%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||||
| Diabetes mellitus | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Hypercalcaemia | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Cachexia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Hyperglycaemia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 1/57 (1.8%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Myalgia | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Seronegative arthritis | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Back pain | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Metastases to gastrointestinal tract | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Metastases to peritoneum | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Penile squamous cell carcinoma | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Depression | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Dyspnoea | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Pulmonary embolism | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Petechiae | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||||
| Combination Phase | Maintenance Phase - Functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, Lanreotide | Maintenance Phase - Non-functioning NET, No Treatment | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 52/57 (91.2%) | 9/11 (81.8%) | 13/14 (92.9%) | 11/12 (91.7%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 7/57 (12.3%) | 9 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 3/12 (25%) | 3 |
| Coagulopathy | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 2 | 0/12 (0%) | 0 |
| Leukocytosis | 1/57 (1.8%) | 2 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Leukopenia | 6/57 (10.5%) | 8 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 3/12 (25%) | 3 |
| Lymphadenopathy | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Lymphopenia | 8/57 (14%) | 10 | 0/11 (0%) | 0 | 2/14 (14.3%) | 2 | 4/12 (33.3%) | 8 |
| Neutropenia | 6/57 (10.5%) | 7 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Thrombocytopenia | 16/57 (28.1%) | 28 | 1/11 (9.1%) | 1 | 3/14 (21.4%) | 3 | 0/12 (0%) | 0 |
| Cardiac disorders | ||||||||
| Arrhythmia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Atrial thrombosis | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Atrioventricular block | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Bradycardia | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Cardiac failure | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Diastolic dysfunction | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Mitral valve incompetence | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Palpitations | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Tricuspid valve incompetence | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Ventricular extrasystoles | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 2/14 (14.3%) | 2 | 1/12 (8.3%) | 1 |
| Ear and labyrinth disorders | ||||||||
| Tinnitus | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Vertigo | 3/57 (5.3%) | 6 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Endocrine disorders | ||||||||
| Hypothyroidism | 1/57 (1.8%) | 1 | 1/11 (9.1%) | 1 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Eye disorders | ||||||||
| Ocular vascular disorder | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Photopsia | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Gastrointestinal disorders | ||||||||
| Abdominal pain upper | 3/57 (5.3%) | 3 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Abdominal discomfort | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Abdominal distension | 4/57 (7%) | 7 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Abdominal pain | 12/57 (21.1%) | 22 | 2/11 (18.2%) | 3 | 4/14 (28.6%) | 6 | 2/12 (16.7%) | 2 |
| Anal inflammation | 1/57 (1.8%) | 2 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Ascites | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Constipation | 11/57 (19.3%) | 16 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Diarrhoea | 21/57 (36.8%) | 35 | 0/11 (0%) | 0 | 3/14 (21.4%) | 4 | 2/12 (16.7%) | 2 |
| Dyspepsia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Eructation | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Faecal incontinence | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Flatulence | 10/57 (17.5%) | 16 | 1/11 (9.1%) | 1 | 2/14 (14.3%) | 3 | 1/12 (8.3%) | 1 |
| Frequent bowel movements | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Intestinal ischaemia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Lip dry | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Melaena | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Nausea | 24/57 (42.1%) | 55 | 1/11 (9.1%) | 1 | 4/14 (28.6%) | 5 | 1/12 (8.3%) | 1 |
| Pancreatic insufficiency | 1/57 (1.8%) | 1 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Steatorrhoea | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Vomiting | 19/57 (33.3%) | 40 | 1/11 (9.1%) | 1 | 2/14 (14.3%) | 3 | 1/12 (8.3%) | 1 |
| General disorders | ||||||||
| Administration site extravasation | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Asthenia | 3/57 (5.3%) | 3 | 1/11 (9.1%) | 1 | 2/14 (14.3%) | 2 | 1/12 (8.3%) | 1 |
| Chest discomfort | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 2 | 0/12 (0%) | 0 |
| Fatigue | 19/57 (33.3%) | 32 | 2/11 (18.2%) | 2 | 4/14 (28.6%) | 4 | 5/12 (41.7%) | 7 |
| Feeling cold | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| General physical health deterioration | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Injection site pain | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Oedema peripheral | 4/57 (7%) | 4 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 2/12 (16.7%) | 2 |
| Pain | 2/57 (3.5%) | 2 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Pyrexia | 4/57 (7%) | 5 | 1/11 (9.1%) | 1 | 3/14 (21.4%) | 4 | 3/12 (25%) | 8 |
| Thirst | 1/57 (1.8%) | 1 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Hepatobiliary disorders | ||||||||
| Cholangitis | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 2 | 0/12 (0%) | 0 |
| Hepatic pain | 3/57 (5.3%) | 3 | 2/11 (18.2%) | 2 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Infections and infestations | ||||||||
| Bronchitis | 1/57 (1.8%) | 1 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Nasopharyngitis | 7/57 (12.3%) | 8 | 3/11 (27.3%) | 4 | 2/14 (14.3%) | 3 | 3/12 (25%) | 3 |
| Otitis media | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Respiratory tract infection | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Sinusitis | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Injury, poisoning and procedural complications | ||||||||
| Fall | 2/57 (3.5%) | 2 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Investigations | ||||||||
| Blood bilirubin increased | 3/57 (5.3%) | 4 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Blood alkaline phosphatase increased | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 2/12 (16.7%) | 2 |
| Blood creatinine increased | 3/57 (5.3%) | 3 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Blood uric acid increased | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| C-reactive protein increased | 2/57 (3.5%) | 4 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Gamma-glutamyltransferase increased | 6/57 (10.5%) | 6 | 1/11 (9.1%) | 2 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Liver function test abnormal | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Platelet count decreased | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Red blood cell count decreased | 1/57 (1.8%) | 1 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Weight decreased | 8/57 (14%) | 8 | 0/11 (0%) | 0 | 2/14 (14.3%) | 2 | 3/12 (25%) | 3 |
| Metabolism and nutrition disorders | ||||||||
| Cachexia | 1/57 (1.8%) | 1 | 1/11 (9.1%) | 1 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Decreased appetite | 3/57 (5.3%) | 3 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Dehydration | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Diabetes mellitus | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Electrolyte imbalance | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Glucose tolerance impaired | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Hypercalcaemia | 2/57 (3.5%) | 2 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Hypercholesterolaemia | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 2/12 (16.7%) | 2 |
| Hyperkalaemia | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 2/14 (14.3%) | 2 | 2/12 (16.7%) | 2 |
| Hypertriglyceridaemia | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 2/12 (16.7%) | 4 |
| Hypocalcaemia | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Hypokalaemia | 3/57 (5.3%) | 3 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Vitamin D deficiency | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 5/57 (8.8%) | 9 | 1/11 (9.1%) | 1 | 2/14 (14.3%) | 2 | 1/12 (8.3%) | 1 |
| Back pain | 2/57 (3.5%) | 2 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 2/12 (16.7%) | 2 |
| Joint swelling | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Muscle tightness | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Musculoskeletal chest pain | 0/57 (0%) | 0 | 1/11 (9.1%) | 4 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Pain in extremity | 3/57 (5.3%) | 3 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Synovial cyst | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Lipoma | 2/57 (3.5%) | 3 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Neoplasm progression | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Tumour pain | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Nervous system disorders | ||||||||
| Carotid arteriosclerosis | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Disturbance in attention | 1/57 (1.8%) | 2 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Dizziness | 3/57 (5.3%) | 6 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 2/12 (16.7%) | 2 |
| Dysgeusia | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 3/14 (21.4%) | 3 | 0/12 (0%) | 0 |
| Headache | 7/57 (12.3%) | 9 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Hypoaesthesia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Polyneuropathy | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Presyncope | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Syncope | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 2 |
| Tremor | 1/57 (1.8%) | 2 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Psychiatric disorders | ||||||||
| Depression | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Disorientation | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Insomnia | 3/57 (5.3%) | 3 | 0/11 (0%) | 0 | 2/14 (14.3%) | 2 | 0/12 (0%) | 0 |
| Renal and urinary disorders | ||||||||
| Urinary incontinence | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dysphonia | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Dyspnoea | 3/57 (5.3%) | 6 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Dyspnoea exertional | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Pleural effusion | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Sleep apnoea syndrome | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||
| Dry skin | 0/57 (0%) | 0 | 1/11 (9.1%) | 1 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Erythema | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 0/12 (0%) | 0 |
| Night sweats | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 1 | 1/12 (8.3%) | 1 |
| Pruritus | 2/57 (3.5%) | 2 | 1/11 (9.1%) | 1 | 2/14 (14.3%) | 2 | 0/12 (0%) | 0 |
| Rash | 5/57 (8.8%) | 6 | 2/11 (18.2%) | 2 | 2/14 (14.3%) | 2 | 1/12 (8.3%) | 1 |
| Vascular disorders | ||||||||
| Flushing | 1/57 (1.8%) | 1 | 0/11 (0%) | 0 | 0/14 (0%) | 0 | 1/12 (8.3%) | 1 |
| Haematoma | 3/57 (5.3%) | 5 | 1/11 (9.1%) | 3 | 0/14 (0%) | 0 | 0/12 (0%) | 0 |
| Hypertension | 5/57 (8.8%) | 5 | 1/11 (9.1%) | 1 | 2/14 (14.3%) | 2 | 2/12 (16.7%) | 2 |
| Lymphoedema | 0/57 (0%) | 0 | 0/11 (0%) | 0 | 1/14 (7.1%) | 2 | 0/12 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
No publication of the Study Results shall be made without the Sponsor's prior written approval which shall not be unreasonably withheld. Sponsor must be provided with the final version of any abstract, presentation or paper before submission, and the Sponsor shall provide scientific comments within 2 weeks for an abstract or presentation or 6 weeks for an article. If no comments are received within these periods, this silence of Sponsor can be considered as approval to proceed to publication.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Ipsen |
| Phone | |
| clinical.trials@ipsen.com |
- A-94-52030-268
- 2013-001697-17