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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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052399 |
E.1.2 | Term | Neuroendocrine tumour |
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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 |
- To compare the proportion of patients without progression between both groups at 48 and 96 weeks, - To compare time to progression in patients with progression between both groups, - To assess the effect of lanreotide Autogel 120 mg compared to placebo on quality of life using EORTC QLQ-C30 and QLQ-GI.NET21 questionnaires, - To assess the effect of lanreotide Autogel 120 mg compared to placebo on plasma chromogranin A and on any other tumour peptide markers with elevated level at baseline and week 48 (Visit 2) - To assess the clinical and biological safety profile of lanreotide Autogel 120 mg, - To assess the putative appearance of lanreotide antibodies, - To 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 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 a World Health Organisation (WHO) performance score lower or equal to 2 - 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), - Has a history of hypersensitivity to drugs with a similar chemical structure - Has been treated with any otherbunlicensed drug within the last 30 days before study entry (visit 1) - Is likely to require treatment during the study with drugs that are not permitted by the study protocol - 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 any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study, and /or evidence of an uncooperative attitude - Has abnormal baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might jeopardise the patient's safety or decrease the chnace of obtaining satisfactory data needed to achieve the objective(s) of the study. - Has been previously enrolled in this 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.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 | 3 |
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 | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
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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 |