E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Non functioning entero-pancreatic tumours |
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E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052399 |
E.1.2 | Term | Neuroendocrine tumour |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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 Autogel120mg
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) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 mitotis/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. |
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E.4 | Principal 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). |
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E.5 End points |
E.5.1 | 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. |
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E.5.1.1 | 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. |
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E.5.2 | Secondary end point(s) |
Porportion of patients without progression or death in each treatment group at 48 and 96 weeks
Time to progress 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 chromogranin 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 assessed at weeks 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
Gall bladder echography at baseline, week 48 and 96
Laboratory tests: standard haematology and biochemistry analysis at screening, baseline, week 48 and 96
Appearance of putative anti-lanreotide antibodies at baseline, week 24, week 48, week 72 and week 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 administrations. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 53 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Belgium |
Czech Republic |
Denmark |
France |
Germany |
Greece |
India |
Italy |
Netherlands |
Poland |
Slovakia |
Spain |
Sweden |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of the trial is defined as the last visit of the last patient undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 3 |