Clinical Trial Results:
A european, multicentre, phase II/III randomised double-blind, placebo controlled study evaluating lanreotide as maintenance therapy in patients with non-resectable duodeno-pancreatic neuroendocrine tumours after first-line treatment
Summary
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EudraCT number |
2013-004069-14 |
Trial protocol |
DE BE IE GB |
Global end of trial date |
22 Jan 2020
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Mar 2022
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First version publication date |
31 Mar 2022
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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
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Sponsor protocol code |
PRODIGE31
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02288377 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Fédération Francophone de Cancérologie Digestive (FFCD)
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Sponsor organisation address |
7 Bd Jeanne d'Arc, Dijon, France, 21000
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Public contact |
Karine Le Malicot, Fédération Francophone de Cancérologie Digestive (FFCD), 33 380393479, karine.le-malicot@u-bourgogne.fr
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Scientific contact |
Karine Le Malicot, Fédération Francophone de Cancérologie Digestive (FFCD), 33 380393479, karine.le-malicot@u-bourgogne.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Apr 2020
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
22 Jan 2020
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Global end of trial reached? |
Yes
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Global end of trial date |
22 Jan 2020
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To evaluate the rate of patients alive and progression free at 6 months, assessed by the investigator according to RECIST criteria, version 1.1.
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Protection of trial subjects |
The study was done in accordance with the Declaration of Helsinki (amended 2000) and the International Conference on Harmonization of Technical Requirements of Pharmaceuticals for Human
Use (ICH) Note for Guidance on Good Clinical Practice and approved by the appropriate Ethics Committees.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Sep 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 2
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Country: Number of subjects enrolled |
Belgium: 1
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Country: Number of subjects enrolled |
France: 50
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Worldwide total number of subjects |
53
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EEA total number of subjects |
51
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
23
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From 65 to 84 years |
30
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85 years and over |
0
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Recruitment
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Recruitment details |
Fifty-three pts were randomised in 15 centres in 3 countries (France, Belgium and UK) between January 2015 and October 2018. | ||||||||||||||||||
Pre-assignment
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Screening details |
Before randomisation, standard examinations (biological, clinical, ECG) and quality of life evaluations (QLQ-C30 + GINET 21) as well as the EQ-5D questionnaire including the Spitzer scale were done. In terms of imaging, chest, abdomen and pelvis CT scan with early arterial timing, or abdominal and pelvic MRI with contrast + chest CT-scan with contr | ||||||||||||||||||
Period 1
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Period 1 title |
Randomized Patients (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Carer, Assessor | ||||||||||||||||||
Blinding implementation details |
In order to guarantee blinding of the investigator and all the staff, all injections were administered by a specifically trained and qualified person (for example, a nurse) otherwise not involved in the study procedures in the centre. Pts were given a randomisation/treatment arm number according to their order of entry into the study by an Interactive Web Response System (IWRS).
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo Arm | ||||||||||||||||||
Arm description |
The study treatment was initiated after randomisation, within the 6 weeks following the confirmation date of stable disease or objective response. Once the randomisation was performed, the patients received a single dose every 4 weeks (every 28 days). | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Injection
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Dosage and administration details |
The placebo injection consisted of a 0.9% saline solution provided as follows:
• A 2 mL ampoule containing 1 mL of NaCl at 0.9%
• An empty syringe of 0.5 ml with an automatic security system and a 20 mm needle of 1.2 mm external diameter and 1.0 mm internal diameter sealed in a laminate bag.
The placebo was stored at the recommended temperature: between +2°C and +8°C. The instructions regarding the subcutaneous product injection were provided in a leaflet accompanying each batch.
Both products were provided by the logistics department of CMC&E, Beaufour IPSEN Industry, 20 rue Ethe Virton, 28100 Dreux (France), and delivered to the study sites.
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Arm title
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Lanreotide Arm | ||||||||||||||||||
Arm description |
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Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
SOMATULINE LP 120 mg
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Injection
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Dosage and administration details |
This treatment was similar to the commercialised form available in France under the name SOMATULINE® LP 120 mg, apart from tertiary packaging and labelling.
Treatment was provided in a pre-filled syringe of 0.5 mL with a 20 mm needle of 1.2 mm external diameter, sealed in a laminated bag and in a cardboard box. Each pre-filled syringe hadan automatic security system.
Each 0.5 mL syringe contained a supersaturated acetate solution of lanreotide corresponding to 0.246 mg of lanreotide base/mg of solution, for subcutaneous injection of a 120 mg dose of lanreotide.
The lanreotide was stored at the recommended temperature: between +2°C and +8°C. The instructions regarding the product injection were provided in a leaflet accompanying each batch.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo Arm
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Reporting group description |
The study treatment was initiated after randomisation, within the 6 weeks following the confirmation date of stable disease or objective response. Once the randomisation was performed, the patients received a single dose every 4 weeks (every 28 days). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanreotide Arm
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Reporting group description |
T | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Placebo Arm
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomised patients in the study who did not withdrew their consent before the randomisation. These patients were considered in the allocated group by randomisation, even if they receive a different treatment.
mITT population was considered as the primary population for efficacy analysis.
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Subject analysis set title |
Lanreotide Arm
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Subject analysis set type |
Modified intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All randomised patients in the study who did not withdrew their consent before the randomisation. These patients were considered in the allocated group by randomisation, even if they receive a different treatment.
mITT population was considered as the primary population for efficacy analysis.
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End points reporting groups
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Reporting group title |
Placebo Arm
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Reporting group description |
The study treatment was initiated after randomisation, within the 6 weeks following the confirmation date of stable disease or objective response. Once the randomisation was performed, the patients received a single dose every 4 weeks (every 28 days). | ||
Reporting group title |
Lanreotide Arm
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Reporting group description |
T | ||
Subject analysis set title |
Placebo Arm
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All randomised patients in the study who did not withdrew their consent before the randomisation. These patients were considered in the allocated group by randomisation, even if they receive a different treatment.
mITT population was considered as the primary population for efficacy analysis.
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Subject analysis set title |
Lanreotide Arm
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
All randomised patients in the study who did not withdrew their consent before the randomisation. These patients were considered in the allocated group by randomisation, even if they receive a different treatment.
mITT population was considered as the primary population for efficacy analysis.
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End point title |
Rate of patients alive without progression at 6 months [1] | ||||||||||||||||||
End point description |
The primary endpoint for phase II is the rate of patients alive and progression free at 6 months, evaluated according to the results of imaging assessment done 6 months after the randomisation. This evaluation is done by the investigator according to RECI
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End point type |
Primary
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End point timeframe |
6 months after the randomisation
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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: The study was a non-comparative study and was stopped prematurely at 53 patients. That's why no statistical analyses was done. |
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No statistical analyses for this end point |
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End point title |
Progression-Free Survival | ||||||||||||
End point description |
PFS was defined as the time between randomisation and the date of the first event (radiological or clinical progression or death). Pts who were alive and progression-free were censored at the time of the last news
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End point type |
Secondary
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End point timeframe |
until the end of the follow-up or the apperance of progression or death
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No statistical analyses for this end point |
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End point title |
Overall Survival | |||||||||||||||
End point description |
Overall survival considered all deaths, and time was calculated from randomisation to death.
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End point type |
Secondary
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End point timeframe |
Until the end of the follow-up or death (Whatever the cause)
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
All AEs (related and unrelated, expected and unexpected) occurring in the course of the study, from the signature of the informed consent form and until 30 days after the last dose of the study drug were reported by the investigator.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Placebo arm
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Reporting group description |
All patients included in the mITT population having received at least one treatment injection. These patients were analysed in terms of the treatment received. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Lanreotide Arm
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Reporting group description |
All patients included in the mITT population having received at least one treatment injection. These patients were analysed in terms of the treatment received. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |