Study to assess the effect of lanreotide Autogel 120 mg compared to placebo on tumour progression free survival in patients with a certain endocrine digestive tumour.

• Register: EUCTR
• Last refreshed on: 30 June 2014
• Main ID: EUCTR2005-004904-35-CZ
• Date of registration: 12/09/2006
• Prospective Registration: Yes
• Primary sponsor: Ipsen Pharma S.A.S
• Public title: Study to assess the effect of lanreotide Autogel 120 mg compared to placebo on tumour progression free survival in patients with a certain endocrine digestive tumour.
• Scientific title: Phase III, randomised, double-blind, stratified comparative, placebo controlled, parallel group, multicentre study to assess the effect of deep subcutaneous injections of lanreotide Autogel 120 mg administered every 28 days on tumour progression free survival in patients with non functioning entero-pancreatic endocrine tumour. - Not applicable
• Date of first enrolment: 15/03/2007
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2005-004904-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: Stratified If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, Czech Republic, Denmark, Germany, Greece, Italy, Netherlands, Spain, Sweden, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
- Provision of written informed consent prior to any study related procedures,
- Male or female of 18 years of age or older,
- Has an endocrine tumour confirmed by centrally assessed histological criteria,
- Has a metastatic disease and/or an locally advanced inoperable tumour, or the patient has refused surgery (documented).
- Has a tumour measurable according to RECIST criteria (central assessment),
- Has no hormone related symptoms,
- Has a non-functioning entero-pancreatic tumour of unknown origin; or with a known primary localisation in the pancreas, mid-gut or hint gut, or a gastrinoma adequately controlled by proton-pump inhibitors (4 months stable prior to study entry).
- Has a well or moderately differentiated tumour (central assessment)
- Has a tumour with proliferation index (Ki67) < 10 % or, in samples where the Ki67 antigen cannot be reliably quantified, a mitotic index = 2 mitosis/10 HPF (central assessment),
- Has a =grade 2 octreoscan assessed using the Krenning scale, during the screening period or within 6 months prior to study entry (Visit 1) for the organ of target lesions
- Has had a biopsy performed within 6 months prior to the screening visit if the patient has had a previous cancer or, if in the opinion of the investigator, there is
evidence of clinical progression
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
- Has been treated with a somatostatin analogue at any time prior to study entry (Visit 1), except if that treatment was for less than 15 days (e.g. peri-operatively) and the treatment was received more than 6 months before study entry (Visit 1),
- Has been treated with a radionuclide at any time prior to study entry (Visit 1),
- Has been treated with interferon, chemoembolisation or chemotherapy within 6 months prior to study entry (Visit 1),
- Has had a previous cancer (except basocellular carcinoma of the skin and/or in situ carcinoma of the cervix/uterus and/or patients treated with curative intent and free from disease for more than 5 years),
- Is at risk of pregnancy or is lactating. Females of childbearing potential must provide a negative pregnancy test at study entry (visit 1) and must be using oral, double barrier or injectable contraception. Non childbearing potential is defined as post-menopausal for at least 1 year, surgical sterilisation or hysterectomy at least three months before the start of the study.
- Has had major surgery related to the studied disease within 3 months prior to entering the study.
- Has a multiple endocrine neoplasia (MEN)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Non functioning entero-pancreatic tumours
MedDRA version: 13.1 Level: PT Classification code 10052399 Term: Neuroendocrine tumour System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

Intervention(s)

Trade Name: SOMATULINE AUTOGEL 120 MG
Product Name: Lanreotide Autogel 120 mg
Pharmaceutical Form: Solution for injection
INN or Proposed INN: lanreotide
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 120-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Primary end point(s): The primary endpoint will be time to either disease progression (measured using RECIST criteria) or death, within 96 weeks after first study treatment administration.

Main Objective: The main objective is to assess the effect of lanreotide Autogel 120 mg administered every 28 days compared to placebo, on progression-free survival in patients with well or moderately differentiated non functioning entero-pancreatic endocrine tumour.

Secondary Objective: Compare the proportion of patients without progression between both groups at 48 and 96 weeks
Compare time to progression in patients with progression between both groups
Assess OS in this patient population
Assess the effect of lanreotide Autogel120mg compared to placebo on quality of life using EORTC QLQ-C30 and QLQ-GI.NET21 questionnaires
Assess the effect of lanreotide Autogel120mg compared to placebo on plasma chromogranin A and on any other tumour peptide markers with elevated level at baseline and week 48 (Visit 2)
Assess the clinical and biological safety profile of lanreotide Autogel 120 mg
Assess the putative appearance of lanreotide antibodies,
Assess the pharmacokinetic profile of lanreotide Autogel 120 mg
In addition characterization of tumour somatostatin receptors profile may also be assessed. This will be proposed to all patients on an optional basis (i.e. each patient will have the opportunity to consent or not on this specific assessment)

Timepoint(s) of evaluation of this end point: The primary endpoint will be time to either disease progression (measured using RECIST criteria) or death, within 96 weeks after first study treatment administration.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please see section E.5.2 above

Secondary end point(s): Proportion of patients without tumour progression or death in each treatment group at 48 and 96 weeks
Time to progression in each treatment group
Overall survival defined as the time from first study treatment administration to death due to any cause
Quality of life using EORTC, QLQ-C30 and QLQ-GI.NET21 at baseline and weeks 12, 24, 36, 48, 72 and 96
Plasma chromograin A level at baseline and weeks 12, 24, 36, 48, 60, 72, 84 and 96
Tumour markers (pancreatic polypeptide, gastrin, VIP, glucagon, somatostatin, insulin neurotensin and urinary 5-HIAA) levels at baseline and weeks 48 and 96. In addition any tumour marker above normal range at baseline will be assessed at weeks 12, 24, 36, 60, 72 and 84 and any tumour marker above normal range at week 48 will be assess at week 60, 72 and 84
AE information will be recorded for each patient throughout the study vital signs, physical examination at each study visit from screening to study completion
ECG at baseline week 48 and week 96
Gallbladder echography at baseline week 48 and week 96
Laboratory tests: standard haematology and biochemistry analyses at screening, baseline, week 48 and 96
Appearance of putative anti-lanreotide antibodies at baseline, weeks 24, 48, 72 and 96
Lanreotide serum concentration at baseline and weeks 4, 12, 24, 36, 48, 72 and 96 (Cw4, Cw12, Cw24, Cw36, Cw48, Cw72 and Cw96 respectively)
Pharmacokinetic profile after the 1st and 6th administration

Secondary ID(s)

2005-004904-35-GB

Protocol 2-55-52030-726

Source(s) of Monetary Support

Ipsen Pharma S.A.S