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Clinical Trial Results:
Phase II, open, single group, multicentre study to evaluate the efficacy and safety of Lanreotide Autogel® (120 mg) administered every 4 weeks by deep subcutaneous injection in the tumour´s growth stabilization of patients with progressive neuroendocrine tumours who are not eligible to be treated with either surgery or chemotherapy
Summary | |
EudraCT number | 2004-002871-18 |
Trial protocol | ES |
Global end of trial date | 06 Nov 2009 |
Results information | |
Results version number | v1(current) |
This version publication date | 14 May 2016 |
First version publication date | 14 May 2016 |
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification | |||
Sponsor protocol code | A-92-52030-166 | ||
Additional study identifiers | |||
ISRCTN number | - | ||
US NCT number | - | ||
WHO universal trial number (UTN) | - | ||
Sponsors | |||
Sponsor organisation name | Ipsen Pharma | ||
Sponsor organisation address | 65, Quai Georges Gorse, Boulogne-Billancourt Cedex, France, 92650 | ||
Public contact | Medical Director, Neurosurgery., Ipsen Pharma, clinical.trials@ipsen.com | ||
Scientific contact | Medical Director, Neurosurgery., Ipsen Pharma, clinical.trials@ipsen.com | ||
Paediatric regulatory details | |||
Is trial part of an agreed paediatric investigation plan (PIP) | No | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? | No | ||
Results analysis stage | |||
Analysis stage | Final | ||
Date of interim/final analysis | 23 Dec 2010 | ||
Is this the analysis of the primary completion data? | Yes | ||
Primary completion date | 06 Nov 2009 | ||
Global end of trial reached? | Yes | ||
Global end of trial date | 06 Nov 2009 | ||
Was the trial ended prematurely? | No | ||
General information about the trial | |||
Main objective of the trial | To evaluate the efficacy of Somatulina Autogel® in tumour growth stabilisation, in patients with progressive neuroendocrine tumours who are not eligible to be treated with either surgery or chemotherapy at the time of their inclusion in the study. | ||
Protection of trial subjects | This clinical study was designed and implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations Title 21 and with the ethical principles laid down in the Declaration of Helsinki. | ||
Background therapy | - | ||
Evidence for comparator | - | ||
Actual start date of recruitment | 05 May 2006 | ||
Long term follow-up planned | Yes | ||
Long term follow-up rationale | Safety, Efficacy | ||
Long term follow-up duration | 22 Months | ||
Independent data monitoring committee (IDMC) involvement? | No | ||
Population of trial subjects | |||
Number of subjects enrolled per country | |||
Country: Number of subjects enrolled | Spain: 30 | ||
Worldwide total number of subjects | 30 | ||
EEA total number of subjects | 30 | ||
Number of subjects enrolled per age group | |||
In utero | 0 | ||
Preterm newborn - gestational age | 0 | ||
Newborns (0-27 days) | 0 | ||
Infants and toddlers (28 days-23 months) | 0 | ||
Children (2-11 years) | 0 | ||
Adolescents (12-17 years) | 0 | ||
Adults (18-64 years) | 17 | ||
From 65 to 84 years | 13 | ||
85 years and over | 0 |
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Recruitment | |||||||||||||||||||||
Recruitment details | Thirty patients from 17 Spanish investigational centres were included in this study, with a maximum of four patients recruited by each of three centres. | ||||||||||||||||||||
Pre-assignment | |||||||||||||||||||||
Screening details | Thirty patients were screened and all thirty were included in the study. | ||||||||||||||||||||
Period 1 | |||||||||||||||||||||
Period 1 title | Overall Trial (overall period) | ||||||||||||||||||||
Is this the baseline period? | Yes | ||||||||||||||||||||
Allocation method | Non-randomised - controlled | ||||||||||||||||||||
Blinding used | Not blinded | ||||||||||||||||||||
Arms | |||||||||||||||||||||
Arm title | All Subjects | ||||||||||||||||||||
Arm description | Lanreotide Autogel 120mg | ||||||||||||||||||||
Arm type | Experimental | ||||||||||||||||||||
Investigational medicinal product name | Lanreotide Autogel | ||||||||||||||||||||
Investigational medicinal product code | |||||||||||||||||||||
Other name | |||||||||||||||||||||
Pharmaceutical forms | Solution for injection | ||||||||||||||||||||
Routes of administration | Subcutaneous use | ||||||||||||||||||||
Dosage and administration details | Lanreotide Autogel 120 mg single deep subcutaneous (s.c.) injection every 4 week (28±5 days) intervals up to 23 doses | ||||||||||||||||||||
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Baseline characteristics reporting groups | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | Overall Trial | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | Lanreotide Autogel 120 mg single deep subcutaneous (s.c.) injection every 4 week (28±5 days) intervals up to 23 doses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups | |||
Reporting group title | All Subjects | ||
Reporting group description | Lanreotide Autogel 120mg |
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End point title | Median time to disease progression [1] | ||||||||||
End point description | Time until disease progression according to the Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 criteria. Disease progression was defined as the occurrence, while on treatment with lanreotide Autogel, of one or more new lesions; a ≥20% increase in the sum of the maximum diameters of the “target lesions”, taking as reference the lowest sum of maximum diameters recorded since the start of the study; or unequivocal progression of “nontarget lesions” ITT population | ||||||||||
End point type | Primary | ||||||||||
End point timeframe | Time between study inclusion until disease progression (Up to Visit 24) | ||||||||||
Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Data reported for single arm, due to system limitation, statistical analysis details cannot be reported | |||||||||||
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No statistical analyses for this end point |
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End point title | Percentage of reduction of the Serum Chromogranin A as compared to the baseline | ||||||||||||||||||||||||
End point description | Patients with Normalised and/or Decrease ≥30% in Serum Chromogranin A (CgA) Concentration at Each Visit ITT population Mc Nemar's Test p values: week 8 (Visit 3) = 0.0002, week 20 (Visit 6) = 0.0027, week 32 (Visit 9) = 0.0082, week 44 (Visit 12) = 0.0253, week 56 (Visit 15) = 0.0253, week 68 (Visit 18) = 0.0455, week 80 (Visit 21) =0.0833 and week 92 (Visit 24) = 0.1573 | ||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||
End point timeframe | At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92 | ||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Factors Predictive of Tumour Growth Control for Cox regression | ||||||||||||||||||||||||||||||||||||||||||
End point description | To identify the factors predictive of tumour growth control on treatment with lanreotide Autogel ® ITT population The values reported are Hazard ratio (95% confidence interval) func (functionality) Cox regression p values: Age = 0.8267, Sex = 0.7232, Presence or absence of tumour functionality = 0.0354, ECOG scale = 0.9453, Tumour origin - FOREGUT (REF:UNKNOWN) = 0.0809, Tumour origin - MIDGUT (REF:UNKNOWN) = 0.0323, Tumour origin - MIDGUT (REF:FOREGUT) = 0.4457, Time between tumour diagnosis and study inclusion = 0.2562, Ki-67 index rank = 0.0890, Initial tumour mass = 0.3639, Previous treatment of the tumour: Chemotherapy = 0.9019, Previous treatment of the tumour: Interferon = 0.8273, Previous treatment of the tumour: Radiotherapy = 0.7576, Previous treatment of the tumour: Somatostatin = 0.8946, Previous treatment of the tumour: Surgery = 0.9727, Lanreotide serum levels = 0.7470, CgA response (ref: Yes) = 0.5869 | ||||||||||||||||||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||||||||||||||||||
End point timeframe | Duration between study inclusion and the date of the last assessment with a response at “stable disease” (Up to Visit 24) | ||||||||||||||||||||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Factors Predictive of Progression Free Survival for Cox regression | ||||||||||||||||||||||||||||||||||||||||||
End point description | To identify the factors predictive of PFS on treatment with lanreotide Autogel ® ITT population The values reported are Hazard ratio (95% confidence interval) func (functionality) Cox regression p values: Age = 0.3669, Sex = 0.4633, Presence or absence of tumour functionality = 0.1214, ECOG scale = 0.1961, Time between tumour diagnosis and study inclusion = 0.3968, Ki-67 index rank = 0.0178, Initial tumour mass = 0.9933, Previous treatment of the tumour: Chemotherapy = 0.3175, Previous treatment of the tumour: Interferon = 0.7742, Previous treatment of the tumour: Radiotherapy = 0.7733, Previous treatment of the tumour: Somatostatin = 0.8288, Previous treatment of the tumour: Surgery = 0.9416, Lanreotide serum levels = 0.5550, CgA response (ref: Yes) = 0.9959, Tumour origin - FOREGUT (REF:UNKNOWN) = 0.1457, Tumour origin - MIDGUT (REF:UNKNOWN) = 0.0694, Tumour origin - MIDGUT (REF:FOREGUT) = 0.5111 | ||||||||||||||||||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||||||||||||||||||
End point timeframe | Duration between study inclusion and the date of disease progression (Up to Visit 24) | ||||||||||||||||||||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Number of subjects with Partial or Complete Response of the Tumoural Lesions | ||||||||||
End point description | ITT population Complete response (CR): Disappearance of all “target lesions” and “nontarget lesions”, and normalisation of tumour marker concentrations. Partial response (PR): A reduction of at least 30% of the sum of maximum diameters of the “target lesions” taking as reference the baseline maximum diameters, and/or disappearance of all the “target lesions” with persistence of one or more “nontarget lesions” and/or tumour markers over the limits of the disease. | ||||||||||
End point type | Secondary | ||||||||||
End point timeframe | Up to Visit 24 (Week 92) | ||||||||||
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No statistical analyses for this end point |
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End point title | Mean Change from Baseline of sum of the Longest Diameter of the target lesions | ||||||||||||||||||||||||
End point description | ITT population | ||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||
End point timeframe | At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92 | ||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Mean change from Baseline of Maximum Decrease or Minimum Increase of the Longest Diameter of the target lesions | ||||||||||
End point description | ITT population | ||||||||||
End point type | Secondary | ||||||||||
End point timeframe | At Baseline (Visit 0) and week 92 (visit 24) | ||||||||||
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No statistical analyses for this end point |
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End point title | Mean Percentage Change from Baseline of Other Tumour Markers: Urinary 5-HIAA | ||||||||||||||||||||||||
End point description | ITT population 5-HIAA (5- hydroxyindole acetic acid) Student's test values: week 8 (Visit 3) = 0.0006, week 20 (Visit 6) = 0.0005, week 56 (Visit 15) = 0.0220, week 68 (Visit 18) = 0.5820; Wilcoxon's test values: week 32 (Visit 9) = 0.4697, week 44 (Visit 12) = 0.3223; Within-group test Not done at week 80 (Visit 21) and week 92 (Visit 24) | ||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||
End point timeframe | At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92 | ||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Baseline Mean And Change in Mean of QLQ-C30 by Five Functional Scale | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description | The QLQ-C30 is composed of both multi-item scales and single item measures. These include five functional scales (physical [PF], role [RF], emotional [EF], cognitive [CF] and social [SF]) QLQ-C30 (Quality of Life Questionnaire) ITT population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe | At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Baseline Mean And Change in Mean of QLQ-C30 Three Symptom Scale | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description | The QLQ-C30 is composed of both multi-item scales and single item measures. These include three symptom scales (fatigue [FA], nausea and vomiting[NV], and pain [PA]). QLQ-C30 (Quality of Life Questionnaire) ITT population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe | At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Baseline Mean And Change in Mean of QLQ-C30 Six Single Scale | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description | The QLQ-C30 is composed of both multi-item scales and single item measures. These include six single items (dyspnoea [DY], insomnia/sleep disturbance [SL], appetite loss [AP], constipation [CO], diarrhoea [DI] and financial difficulties [FI]). QLQ-C30 (Quality of Life Questionnaire) ITT population | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point timeframe | At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Baseline Mean And Change in Mean of QLQ-C30 Global Quality Of Life Scale | ||||||||||||||||||||||||||
End point description | The QLQ-C30 is composed of both multi-item scales and single item measures. ITT population | ||||||||||||||||||||||||||
End point type | Secondary | ||||||||||||||||||||||||||
End point timeframe | At Baseline (Visit 0), week 8, 20, 32, 44, 56, 68, 80 and 92 | ||||||||||||||||||||||||||
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No statistical analyses for this end point |
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End point title | Number of Subjects With Symptomatic Control related to Neuroendocrine Tumours During The Treatment Period | ||||||||||||||||
End point description | Evaluation of the symptom control ITT population NET (Neuroendocrine tumours) | ||||||||||||||||
End point type | Secondary | ||||||||||||||||
End point timeframe | Up to Visit 24 (Week 92) | ||||||||||||||||
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No statistical analyses for this end point |
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Adverse events information | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events | Up to visit 24 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type | Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name | MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version | 11.1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title | All Subjects | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description | Safety population: includes all patients who have received at least one dose of Somatuline Autogel® (same definition as ITT population) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) | |||
Were there any global substantial amendments to the protocol? Yes | |||
Date | Amendment | ||
23 Feb 2006 | Two new centers has been incorporated. To do faster the procedure to assign randomization codes to radiological copies. | ||
Interruptions (globally) | |||
Were there any global interruptions to the trial? No | |||
Limitations and caveats | |||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |